A i ia, i i , is yoas an a EAT Uaneenee Pay A Oe f Ke Beate am il) SO Rae Ci ed RK ATE WO RCA Ai Se in An en Py CORNELL UNIVERSITY LIBRARY BOUGHT WITH THE INCOME OF THE SAGE ENDOWMENT FUND GIVEN IN 1891 By HENRY WILLIAMS SAGE ————— “Nicngana A LABORATORY MANUAL AND TEXT-BOOK of EMBRYOLOGY By CHARLES WILLIAM PRENTISS, A. M., Pu. D. LATE PROFESSOR OF MICROSCOPIC ANATOMY, NORTHWESTERN UNIVERSITY MEDICAL SCHOOL, CHICAGO Revised and Extensively Rewritten by LESLIE BRAINERD AREY, Pu. D. ASSOCIATE PROFESSOR OF ANATOMY IN THE NORTHWESTERN UNIVERSITY MEDICAL SCHOOL, CHICAGO SECOND EDITION, ENLARGED WITH 388 ILLUSTRATIONS MANY IN COLOR PHILADELPHIA AND LONDON W. B. SAUNDERS COMPANY 1917 Copyright, 1915, by W. B. Saunders Company. Reprinted August, 1915. Revised, entirely reset, reprinted, and recopyrighted October, 1917 Copyright, ror7, by W. B. Saunders Company PRINTED IN AMERICA PRESS OF W. &. SAUNDERS COMPANY PHILADELPHIA PREFACE TO THE SECOND EDITION THE untimely death of Professor Prentiss has made necessary the transfer of his ‘Embryology’ into other hands. In this second edition, however, the general plan and scope of the book remain unchanged although the actual descrip- tions have been extensively recast, rewritten, and rearranged. A new chapter on the Morphogenesis of the Skeleton and Muscles covers briefly a subject not included hitherto. Forty illustrations replace or supplement certain of those in the former edition. In preparing the present manuscript a definite attempt has been made to render the descriptions as clear and consistent as is compatible with brevity and accuracy. It has likewise been essayed to properly evaluate the embryological contributions of recent years, and, by incorporating the fundamental advances, to indicate the trend of modern tendencies. Since no page remains in its entirety as originally penned by Professor Prentiss, the reviser must assume full respon- sibility for the subject-matter as it now stands. It is hoped that those who read this text will co-operate with the writer by freely offering criticisms and suggestions. L. B. A. Curcaco, ILL., October, 1917. lil PREFACE Tus book represents an attempt to combine brief descriptions of the verte- brate embryos which are studied in the laboratory with an account of human embryology adapted especially to the medical student. Professor Charles Sedg- wick Minot, in his laboratory textbook of embryology, has called attention to the value of dissections in studying mammalian embryos and asserts that “dissection should be more extensively practised than is at present usual in embryological work. .” The writer has for several years experimented with methods of dissecting pig embryos, and his results form a part of this book. The value of pig embryos for laboratory study was first emphasized by Professor Minot, and the development of my dissecting methods was made possible through the reconstructions of his former students, Dr. F. T. Lewis and Dr. F. W. Thyng. The chapters on human organogenesis were partly based on Keibel and Mall’s Human Embryology. We wish to acknowledge the courtesy of the pub- lishers of Kollmann’s Handatlas, Marshall’s Embryology, Lewis-Stéhr’s Histology and McMurrich’s Development of the Human Body, by whom permission was granted us to use cuts and figures from these texts. We are also indebted to Professor J. C. Heisler for permission to use cuts from his Embryology, and to Dr. J. B. De Lee for several figures taken from his “Principles and Practice of Obstetrics.” The original figures of chick, pig and human embryos are from preparations in the collection of the anatomical laboratory of the Northwestern University Medical School. My thanks are due to Dr. H. C. Tracy for the loan of valuable human material, and also to Mr. K. L. Vehe for several reconstruc- tions and drawings. C. W. PRENTISS. NORTHWESTERN UNIVERSITY MEDICAL SCHOOL. CONTENTS PAGE TINTRODUCTIONS 45 cco-was. spud aaie eagnarcyoraieratitis# ache Gilosacean aca SR aeanend ns Gia gs & Sade sear ean ea est 1 CHAPTER U— Tn, ‘GERM OBELS: sfrdiagn ap iararsat ena docseia he ke paar hen a oa saan eG 7 SEM OV ATA a tee ahah ceva rsinic oeiutcendds peat w ect ae rama ded reese nee uaoed tains ama auasumnate Gea BERRI ite aes 7 Ovulationsand: Menstruation’: 05.005 Wwe ocala bu no Mao han eigen hahaa pyar lanes eo se 10 ENE SPEEMALOZOON ys sacs dor a Mee ns oe cree Peet net eens boner ewes Cees wan eh3 10 Mitosis and: Amiltosiss: ea iy yg ccc bu od £gacadaon ba wes daheoewiaydrar ob cnsete node Biusedaranes ae 12 IME aetna ti Omer: § sarte a ate eececte wthceisuy nd 2 Tena BELG Dea Maw hen ee DS aE Tad he kMestoeuae Saal! 14 OTE IZA C1 OT a shasticga:d ous sg eed mE aspohoanais malas GAL cas Bohs dtades Be MaMa UN aaa ay Sd, oe Seis etd Oaridauanee eetned4 19 Heredity and the Determination of Sex... 0... 0.0.00. nen nbn nen tenes 21 CHAPTER IT.—CLEAVAGE AND FORMATION OF THE GERM LAYERS.............-..22000000 0000s 23 Cleavage in Amphioxus, Amphibia, Birds, and Reptiles............0..0....0000 00220000 23 Cleavage win Miaminiall Sites ie Anant wa kr ila oma egies aud seen Alas aba hohds ouainainewicinanmn nent a 26 Origin of the Metoderm and! Entoderm. 9.x nex dx fede Alnaibeoe say eee eg ogo ead 4 28 Origin of the Mesoderm, Notochord and Neural Tube................0 00000. e cece 29 Whe: Notochond)s 4%. ccte"s eed 2 oe S22 es ri ale gga ane a nee oo eas ae Aes 35 CHAPTER III].—TuHe Stupy or CHIcK EMBRYOS. ........200 0000 c cece eee 36 Chick: Embryoof Twenty Hoursé cc. .cn acu au 64 ak Sane Rodd dd eka cheka Thea ed 36 Chick Embryo of Twenty-five Hours (7 Segments)... 0.2.0... 0c eee eee eee 38 ATATIS VETSE SECEONS ce cecccy alas shy Sey ee dioerreanetire tdl ac elevates A eeR nce aunaned Wlunees Wea Ea ANCES 40 Chick Embryo of Thirty-eight Hours (17 segments)... ... 0.00.00. 0 0000000 cece eee eee 43 Gemerall Amato in iy cts, wera esta Baiciavs inh aeisde exsetelic hte avis cot MAMMA ape iebea td alee ate a eave clalinina ae 43 PraANSVerSesSECHONSH fats angi syiadiisay eas aad oanshieaedthn ad» anes Pen gia clonmeshineitnds 47 Derivatives:oh the Germ Layers’ oc. a5 2c0 5 ges ose deb eases se oe ee eR eae bn eee 54 Chick Embryo of Fifty Hours (27 segments)... 00000 cece ee eene 55 General Anatomy y's aoch lenny vgs howe eevee steam se eo ERE Ee eed ees awe deelahee 55 Tratisverse-Sections sa. ices aioe ga sareka 2 oc RG dd eeoweding aes Cea be Aka BOS Sabana Aa 59 CHAPTER IV.—TuHeE FETAL MEMBRANES AND EARLY HUMAN EMBRYOS...............0..00000- 68 Fetal Membranes of the Pig: Embryo)... gocc3 0 teen wa tiuautaadeh ogous Soave wid bobs Aya Rds ded ened 68 Wim Diliea Conds coe 3.8 6 ects eee ay Sy 5 cc oy op acted decide decent WMO epi ty Reto lala dea pense gh eataNG 70 Early Human Embryos and Their Membranes... ..........0.00 0000 e eee eee 71 Anatomy of a 4.2 mm. Human Embryo... 2.0.0... 79 Age iok Humanck mbtyOSa 1k dai aiid Ames 4 eed aoe dois nom ned oe Moaung nina tian aaa 87 CaAPTER V.—THE STUDY OF PIG EMBRYOS vcd dust e ached GRA MAAGE Ses OY eaaak eed oem benel 89 The Anatomy of a 6 mm. Pig Embryo... 1.0.0... cnet eee eens 89 External Form and Internal Anatomy... ... 0.0... 0... cece ccc e eee nen . 89 PLPANSVCLSE SE CHO MS) 56 pict asec ssccutn stipes ie dh Sem Sie Vem e Pusyale BosiGnacensuuameo nana mtecd olgh & docsters 104 The Anatomy of 10-12 min. Pig EMbEV OS! 4 .0 ie econ esac Koln a doe dae knw eminaueee 112 External Form and Internal Anatomy... .............00 00020 cece eee eee a ae OLED, -BTAMSV CESE SECTIONS 5 ca vutrd aiwasuwnraidn ie oe hesunbune Bue ors Seneetelacei aes hae ieeielslale, deat ENA 125 CHAPTER VI.—MEeEtTHops oF DissEcTING Pic EmBryos: DEVELOPMENT OF THE FACE, PALATE, ToncurE, TEETH AND SALIVARY GLANDS... 00... es 137 Directions for Dissecting Pig Embryos... . 0.0.2.2... 000006 e ccc eee eee ee 137 Dissections of 18-35 mm. Embryos... 0.0.0.0... o occ eee e eee e ees 140 Development: Of the Faces 552 sca hacen an Wino sot dada ait edb nd deanordaettapabeentfaiedd ta edaueed & Aameateten teases 144 Development ofthe: Hard: Palate: 3: cana t5.2-kasee eet tape coed meedelaleeedd ubedharan toh. dobsesbchen cop an atime ses 146 Development: of the Tong tei. .s 0 oe echaate! vaste aod once: beta a euenicngudega aitwrn ow geaee wavesnd Dab eheAende 149 Developmentofthe: salivary Glands... cis scciceem data om aeivein Wa baal eau: + coy ieee y 152 Development ofthe: Feethe icc ncsaw aecniet 4 ancnn yey, veel erate oe. Hs gee Gonans Pa ements 153 vili CONTENTS PAGE CHAPTER VIT.—ENTODERMAL CANAL AND ITS DERIVATIVES... 0.00. c cece cece cece eee eee etees 159 Pharyngeal Pouches and their Derivatives. ........00 00... c cece cece cece cece cece etenneee 160 Why reid (Gland. sa sxoseuinen atten th Gk & dts Anal cdskoavae to mhebal matacedna) Wa ove bod ovis a beck Mbeducheuatuaree Meee SAE 164 atynx,; Prachea:and: Ian ese, cs. theca dca yot mont a ators in ndeuedaleoayandcaan dela h ake auteereae ala a ue eS 164 Digestive (Cama lane fc uekco cuyecamalt wes leh atv moe cesslekel all lanes leas RA sen NAME os yao eB Soe 169 Ti OTe sess geen ees 1 Ssbaeteabe he wctchchete Satoh. SD Rdele GSA SOONER ON atone SLaTE He dibudit We eIOA tok ace ch Fe .. 175 DAM Grea Sia tec fs toner eaeeeat ove ids irae a cauoie ictal Mad dosed A tonccttals iain edt a Ach tacos decoherence amet _. 178 Body Cavities, Diaphragm and Mesenteries... 1.2.0.0... 0. cece eee e eee nee ence et eeee 179 CHAPTER VIITL—UROGENITAL- SYSTEMS. 2.555 ne eat a ati Sate bin toe See ee RoR AS SEE OMe 195 PLONE EOS sm seg cosce se @ uses tes ARAN ay Aah cha shen pads ve onte we atesne au Sem le Bia: Slate rethaand Grease Sa Reakeeeeeae .. 195 Miesonephross: a sen Aide wacntdeuee aco aarett iar: alba fl eidlaialntlecitiain acon nainrnben inte ancien a a een oneratra teed 197 Meétanephrosinass oes pass uianeas edie sae PP ede dese gue eye bee ed gence) SORE 199 Cloaca, Bladder, Urethra and Urogenital Sinus.......... 00.0000 0. e ee cece eee ae 205 Genital: Glandsand: Ductsi ss givsi- te pha eee HS eS FLEE OE HONE BOER 4G 8 ABER ES LO eee ae 208 External Gemitania cr, 2 a:6.008 Rosteociciniues wae ae outa IES he Liebe’ PAGE SURES TEAR ESR akg 224 The Uterus during Menstruation and Pregnancy..... 2.0.2... 6.0 o eee 230 The Decidual Membranes...................- relists ptddeesl dB eR OS ren NeA piSauncrer ad Smee tenets 231 CTS er PAGO nit as ocnxa-a a naonserstg? aeesainanceend ves 2 be Suse alge Shc MN ea Ss AAS ayaa aus aug ee tea a Teak a eta 237 The Relation-of Fetus to Placemtais icccc 2 c-cseseie aren au tateciivenncti cone tvere once moda Anal A dies dtc aveale i Gee 241 CHAPTER: IX. VASCUEAR SISTEM :.2 na) pre os PEER: Sea ReRS 14 ee Eee eee teen ee 243 The Primitive Blood Vessels and Blood Cells... 1.2.0.2... 0.0: cc cece cece ee eee eee e eee 243 Development..of the Hearts ccoces cg eae oats Seaa be SR kee eee eRe ee ewes FEE RAS 247 Primitive Blood: Vascular System: 5 ca.cuci008 CHa Mok Pease ae tee oe pee eae pease 259 Developmentiof the-ATteMes.. ooo 5c pode a esa Sdcanb hes Kase eed badonte paeheeteas sae 2061 Deévelopment.of the, VeinSs .ocs co agc00 4 nad A edonlitd a dda adidas Shauinet ced Bepeaueune Eales 268 Bhe: BetalCireulatiomts 2. se ss, so ncterese aoe dace as acbgeeaerni A ore Somnb eases Snpaaamab nad b.8 wee dbeyim 207 The Wey phatie Systems, 4. iesceace seeget onus ciseetiaie waqehennie we ghachn Ptvaand ead AV Qdue DN GDS ie b Suaobpeghghane 279 ymph.and.emolymph'Glandsa.2. 5 <.c0 dau sapreten Gre eaeme nies MAI ead rendned QQdeiine 281 Spleemssnrive-sanhisve sz cateunlaypiay afte feces os Joase gt eure te de Aa 4, ai lvoe oar lbepe adele deep a AR 281 CHAPTER Xi.“ FISTOGENESIS acu s aoeuns saa e ete ween Say tie tae na ae Ubud oa eas emaatians 283 The Entodermal Derivatives ic. ncvreeesagareine ss 22406 A Kane Stee eae was Pewenes 283 ‘Fhe: Mesodermal Tissites)«.¢., accs.40e4 3 npeeeetun Mant Lag eres Gate beta baa ae Came 284 Tae Ectodermal Derivatives. uic.so 3 ca-ccacudawt noe Seedy dee bd eS ee bee ee aes eee 294 The Ne ous: Disses 22. ee ek acd 2 4 04 6 set deardsivacd y BEA d SE die wre hd MGoweNwii ee EE dees Bees 300 CHAPTER XI.—MORPHOGENESIS OF THE SKELETON AND MUSCLES..... 2.2.0... 00000 e eee eeeeee 309 AhesS Ke letale Sy Stem. (tare ec fontun Sek ta tacad vice MegeN@a nk a hisde ten ewiphel een ae adem Ahe Onelselees 309 GRETA SILC TO Ic cf ae eh cs csr eec ke Meagan we sees dsssb ao RaKANHO RONG Ges Sree Serta A EERSMO HS 309 Appendicular Systema. gcc. csgica wen acedeergavemicn yczcm gaat aoangteineaenvard ode RAAB RSE Ea ave re acta ae 0 315 ARES Miuseula ri Sy St emt) wcrc d deahindecn tecieishitheuss AE aa. otal ac seeds vengha sua eee Bly dears esata SS 316 CHAPTER XII.—MorPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM...........0 000000 ee ee eee 321 he: Spinal: Cord: 4s nue shee sey LEBER ES Ment tee gae han aula k et ecns tune ee S27 THE Brain, 44 G vices enn e eee oat nee needa ha high oe wanuien & cud Grito @ ae BOE wat A et aeee 327 The Differentiation of the Subdivisions of the Brain... ...........0.. ccc cece cece eee: 332 CuarTer XIII.—TueE PErIPHerat NERVOUS SYSTEM... 2... ec cece cece eeeevececes 8 353 ABW SPINAL INC TCS scree casters ee of Aa aded pre awtuia iat tahaeete NNT acdc a dancer aodite Meno eRe eae oe A WEEG Creb ral AN EVs egies G8 ak soe ch Soschiunstosabsiala a. tnob uae booed ante aed St The Sympathetic Nervous System... 0.000.000. .0 ccc cece eee nec e cece eueeceenceeeees 366 Chromaffin Bodies: Suprarenal Gland... 00.000. 0 0c cece ccc ccc cece eee eecevecee 368 The Sense Orpamsecscs cease 4.4 aparece va bean wach gia ers eter Gemva dle: sich satirouieban Boles, reciac e m ns tnaeeid a 370 TEXT-BOOK OF EMBRYOLOGY INTRODUCTION THE study of human embryology deals with the development of the individual from the origin of the germ cells to the adult condition. To the medical student human embryology is of primary importance because it affords a comprehensive understanding of gross anatomy. It is on this account that only recently a prominent surgeon has recommended a thorough study of embryology as one of the foundation stones of surgical training. Embryology not only throws light on the normal anatomy of the adult, but it also explains the occurrence of many anomalies, and the origin of certain pathological changes in the tissues. From the theoretical side, embryology is the key with which we may unlock the secrets of heredity, of the determination of sex, and, in part, of organic evolution. There is, unfortunately, a view current among graduates in medicine that the field of embryology has been fully reaped and gleaned of its harvest. On the contrary, much productive ground is as yet unworked, and all well-preserved human embryos are of value to the investigator. An institute of embryology for the purpose of collecting, preserving, and studying human embryos has re- cently been established by Professor F. P. Mall of the Johns Hopkins Medical School. Aborted embryos and those obtained by operation in case of either normal or ectopic pregnancies should always be saved and preserved at once by immersing them intact in 10 per cent. formalin or in Zenker’s fluid. Historical.—The science of modern embryology is a comparatively new one, originating with the use of the compound microscope and developing with the improvement of microscopical technique. Aristotle (384-322 B. c.), however, centuries before had followed the general development of the chick day by day. The belief that slime and decaying matter was capable of giving rise to living animals, as asserted by Aristotle, was disproved by Redi (1668). A few years after Harvey and Malpighi had published their studies on the chick embryo, Leeuwenhoek reported the discovery of the spermatozoén by Ham in 1677. At this period it was believed either that fully formed animals existed in miniature in the egg, needing only the stimulus of the spermatozoén to I 2 INTRODUCTION initiate development, or that similarly preformed bodies, male and female, con- stituted the spermatozoa and that these merely enlarged within the ovum. According to this doctrine of preformation all future generations were likewise encased, one inside the sex cells of the other, and serious computations were made as to the probable number of progeny (200 million) thus present in the ovary of Mother Eve, at the exhaustion of which the human race would end! Dalenpatius (1699) believed that he had observed a minute human form in the spermatozoén. The preformation theory was strongly combated by Wolff (1759) who saw that the early chick embryo was differentiated gradually from unformed living sub- stance. This theory, known as epigenesis, was proved correct when, in 1827, von Baer discovered the mammalian ovum and later demonstrated the germ layers of the chick embryo. About twenty years after Schleiden and Schwann (1839) had shown the cell to be the structural unit of the organism, the ovum and spermatozoon were recog- nized as true cells. O. Hertwig, in 1875, was the first to observe and appreciate the events of fertilization. Henceforth all multicellular organisms were believed to develop each from.a single fertilized ovum, which by continued cell division eventually gives rise to the adult body, containing, it is estimated, 26 million million cells. In the case of vertebrates, the segmenting ovum differentiates first three primary germ layers. The cells of these layers are modified in turn to form tissues, such as muscle and nerve, of which the various organs are composed, and the organs together constitute the organism, or adult body. Primitive Segments—Metamerism.—In studying vertebrate embryos we shall identify and constantly refer to the primitive segments or metameres. These segments are homologous to the serial divisions of an adult earth worm’s body, divisions which, in the earth worm, are identical in structure, each containing a ganglion of the nerve cord, a muscle segment, or myotome, and pairs of blood ves- sels and nerves. In vertebrate embryos the primitive segments are known as mesodermal segments, or somites. Each pair gives rise to a vertebra, to a pair of myotomes, or muscle segments, and to paired vessels; each pair of mesodermal segments is supplied by a pair of spinal nerves, consequently the adult verte- brate body is segmented like that of the earth worm. As a worm grows by the formation of new segments at its tail-end, so the metameres of the vertebrate embryo begin to form in the head and are added tailward. There is this dif- ference between the segments of the worm and the vertebrate embryo. The seg- mentation of the worm is complete, while that of the vertebrate is incomplete ventrally. GROWTH AND DIFFERENTIATION OF THE EMBRYO 3 GROWTH AND DIFFERENTIATION OF THE EMBRYO A multicellular embryo develops by the division of the fertilized ovum to form daughter cells. These are at first similar in structure, and, if separated, any one of them may develop into a complete embryo, as has been proved by the experiments of Driesch on the ova of the sea urchin. The further development of the embryo depends: (1) upon the multiplication of its cells by division; (2) upon the growth in size of the individual cells; (3) upon changes in their form and structure. The first changes in the form and arrangement of the cells give rise to three definite plates, or germ layers, which are termed from their positions the ectoderm (outer skin), mesoderm (middle skin) and entoderm (inner skin). Since the ecto- derm covers the body it is primarily protective in function, but it also gives rise to the nervous system through which sensations are received from the outer world. The entoderm, on the other hand, lines the digestive canal and is from the first nutritive in function. The mesoderm, lying between the other two layers, naturally performs the functions of circulation, of muscular movement, and of excretion; it also gives rise to the skeletal structures which support the body. While all three germ layers form definite sheets of cells known as epithelia, the mesoderm takes also the form of a diffuse network of cells, the mesenchyma. The Anlage.—This German word, which lacks an entirely satisfactory English equivalent, is a term applied to the first discernible cell, or aggregation of cells, which forms any distinct part or organ of the embryo. In the broad sense the fertilized ovum is the anlage of the entire adult organism; furthermore, in the early cleavage stages of certain embryos it is possible to recognize single cells or cell groups from which definite structures will indubitably arise. The term anlage, however, is more commonly applied to the primordia that differentiate from the various germ layers. Thus the thickening of the epithelium over the optic vesicle is the anlage of the lens. | Differentiation of the Embryo.—The developing embryo exhibits a progres- sively complex structure, the various steps in the production of which occur in orderly sequence. There may be recognized in development a number of com- ponent mechanical processes which are used repeatedly by the embryo. The general and fundamental process conditioning differentiation is cell multiplication and the subsequent growth of the daughter cells. The more important of the specific developmental processes are the following: (1) cell migration; (2) localized growth, resulting in enlargements and constrictions; (3) cell aggregation, forming (a) 4 INTRODUCTION cords, (b) sheets, (c) masses ; (4) delamination, i. e., the splitting of single sheets into separate layers; (5) folds, including circumscribed folds which produce (a) evagina- tions, or out-pocketings, e. g., the intestinal villi, (b) cnvaginations, or in-pocket- ings, e. g., the intestinal glands. The production of folds, including evaginations and invaginations, due to un- equal rapidity of growth, is the essential factor in moulding the organs and hence the general form of the embryo. Differentiation of the Tissues.—The cells of the germ layers which form organic anlages may be at first alike in structure. Thus the evagination which forms the anlage of the arm is composed of a single layer of like ectodermal cells, surrounding a central mass of diffuse mesenchyma (Fig. 136). Gradually the ectodermal cells multiply, change their form and structure, and give rise to the layers of the epidermis. By more profound structural changes the mesen- chymal cells also are transformed into the elements’ of connective tissue, tendon, cartilage, bone, and muscle, aggregations of modified cells which are known as tissues. The development of modified tissue cells from the undifferentiated cells of the germ layers is known as histogenesis. During histogenesis the struc- ture and form of each tissue cell are adapted to the performance of some special function or functions. Cells which have once taken on the structure and func- tions of a given tissue cannot give rise to cells of any other type. In tissues like the epidermis, certain cells retain their primitive embryonic characters throughout life, and, by continued cell division, produce new layers of cells which are later cornified. In other tissues all of the cells are differentiated into the adult type, and, during life, no new cells are formed. This takes place in the case of the nervous elements of the central] nervous system. Throughout life, tissue cells are undergoing retrogressive changes. In this way the cells of certain organs like the thymus gland and mesonephros degenerate and largely disappear. The cells of the hairs and the surface layer of the epider- mis become cornified and eventually are shed. Thus, normally, tissue cells may constantly be destroyed and replaced by new cells. The Continuity of the Germ Plasm.—According to this important conception of Weismann the body-protoplasm, or soma, and the reproductive-protoplasm differ fundamentally. The germinal material is a legacy that has existed since the beginning of life, from which representative portions are passed on intact from one generation to the next. Around this germ plasm there develops in each successive generation a short-lived body, or soma, which serves as a vehicle for insuring the transmission and perpetuation of the former. The reason, there- METHODS OF STUDY 5 fore, why offspring resembles its parents is because each develops from portions of the same stuff. The Law of Biogenesis.—Of great theoretical interest is the fact, con- stantly observed in studying embryos, that the individual in its development tends to repeat the evolutionary history of its own species. This law of recapitu- lation was first stated clearly. by Miiller in 1863 and was termed by Haeckel the law of biogenesis. According to this law, the fertilized ovum is compared to a unicellular organism like the Amceba; the blastula is supposed to represent an adult Volvox; the gastrula, a simple sponge; the segmented embryo a worm-like stage, and the embryo with gill slits may be regarded as a fish-like stage. The blood of the human embryo in development passes through stages in which its corpuscles resemble in structure those of the fish and reptile; the heart is at first tubular, like that of the fish; the kidney of the embryo is like that of the amphib- ian, as are also the genital ducts. Many other examples of this law may readily be observed. Methods of Study—Human embryos not being available for individual laboratory work, the embryos of the lower animals which best illustrate certain points are employed instead. Thus the germ cells of Ascaris, a parasitic round worm, are used to demonstrate the phenomena of mitosis and maturation; the larvee of echinoderms, or of worms, are frequently used to demonstrate the cleav- age of the ovum and the development of the blastula and gastrula larve; the chick embryo affords convenient material for the study of the early vertebrate em- bryo, of the formation of the germ layers and of the embryonic membranes, while the structure of a mammalian embryo, similar to that of the human embryo, is best observed in the readily procured embryos of the pig. An idea of the anatomy of embryos is obtained first by examining the exterior of whole embryos and study- ing dissections and reconstructions of them. Finally, each embryo is studied in serial sections, the level of each section being determined by comparing it with figures of the whole embryo. Along with his study of the embryos in the laboratory, the student should do a certain amount of supplementary reading. Only the gist of human organo- genesis is contained in the following chapters. A very complete bibliography of the subject is given in Keibel and Mall’s “Human Embryology,” to which the student is referred. Below are given the titles of some of the more important works on vertebrate and human embryology, to which the student is referred and in which supplementary reading is recommended. 6 INTRODUCTION TITLES FOR REFERENCE Duval, M. Atlas D’Embryologie. Masson, Paris, 1889. His, W. Anatomie menschlicher Embryonen. Vogel, Leipzig, 1885. Keibel, F. Normentafel zur Entwicklungsgeschichte der Wirbelthiere. Bd. I. Fischer, Jena, 1897. Keibel and Elze. Normentafel zur Entwicklungsgeschichte des Menschen, , , , Jena, 1908. Keibel and Mall. Human Embryology. Lippincott, 1910-1912. Kellicott, W. E. A Textbook of General Embryology. Henry Holt, 1913. Kollmann, J. Handatlas der Entwicklungsgeschichte des Menschen. Fischer, Jena, 1907. Lee, A. B. The Microtomist’s Vade Mecum. Blakiston, 1913. Lewis, F.T. Anatomy of a 12 mm. Pig Embryo. Amer. Jour. Anat., vol. 2. Lillie, F. R. The Development of the Chick. Henry Holt, 1908. Minot, C.S. A Laboratory Text-book of Embryology. Blakiston, 1910. Thyng, F.W. The Anatomy of a 7.8mm. Pig Embryo. Anat. Record, vol. 5. Wilson, E. B. The Cell in Development and Inheritance. Macmillan, 1911. CHAPTER I THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION THE GERM CELLS THE highly differentiated human organism, like all other vertebrates and most invertebrates, develops from the union of two germ cells, the ovum and spermatozoon. The Ovum.—The female germ cell, or ovum, is a typical animal cell pro- duced in the ovary. It is nearly spherical in form and possesses a nucleus with nucleolus, chromatin network, chromatin knots, and nuclear membrane (Figs. 1 and 2). The cytoplasm of the ovum is distinctly granular, containing more or less numerous yolk granules and rarely a minute centrosome. The nucleus is essential to the life, growth, and reproduction of the cell. The function of the nucleolus is unknown; the chromatin probably bears the hereditary qualities of the cell. The yolk granules, containing a fatty substance termed Jecithin, furnish nutrition for the early development of the embryo. A relatively small amount of yolk is found in the ova of the higher mammals, since the embryo develops within, and is nourished by, the uterine wall of the mother. A much larger amount occurs in the ova of fishes, amphibia, reptiles, birds, and the primitive mammalia, the eggs of which are laid and develop outside of the body. The so-called yolk of the hen’s egg (Fig. 3) is the ovum proper and its yellow color is due to the large amount of lecithin which it contains. Ova become surrounded by protective membranes, or envelopes. The vitelline membrane, secreted by the egg itself, is a primary membrane (Fig. 2). The follicle cells about the ovum usually furnish other secondary membranes, e. g., the zona pellucida. Tertiary membranes may be added as the egg passes through the oviduct and uterus—the albumen, shell membrane, and shell of the hen’s egg are of this type (Fig. 3). The human ovum is of small size, measuring from 0.22 to 0.25 mm. in diam- eter (Fig. 1). The cytoplasm is surrounded by a relatively thick radially striated membrane, the zona pellucida. The striated appearance of the zona pellucida is said to be due to fine canals which penetrate it and through which nutriment is carried to the ovum by smaller follicle cells during its growth within the ovary. 7 8 THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION The origin and growth of the ovum within the ovary (odgenesis) are described on pp. 214-217. We may state here that each growing ovum is at first surrounded Fic. 1.—Human ovum examined fresh in the liquor folliculi (Waldeyer). > 415. The zona pellu- cida is seen as a thick, clear girdle surrounded by the cells of the corona radiata. The nearly mature egg itself shows a central granular deutoplasmic area and a peripheral clear layer, and encloses the nucleus in which is seen the nucleolus. At the right is a spermatozoén correspondingly enlarged. 2 Ae : your" Fic. 2.—Ovum of monkey. X 430. by small nutritive cells known as follicle cells. These increase in number during the growth of the ovum until several layers surround it (Fig. 229). A cavity appearing between these cells becomes filled with fluid and thus forms a sac, THE GERM CELLS 9 yy. wy. wy. bl Ub. x wW. Fic. 3—Diagrammatic longitudinal section of an un- Fic. 4.—Section of human ovary, incubated hen’s egg (Allen Thomson in Heisler): b.J, germ- including cortex: a, germinal epithe- inal disc; w.y, white yolk, which consists of a central flask- lium of free surface; 6, tunica albu- shaped mass, and a number of concentric layers surrounding ginea; c, peripheral stroma contain- the yellow yolk (y..); v.t, vitelline membrane; x, a some- ing immature Graafian follicles (d); e, what fluid albuminous layer which immediately envelops well-advanced follicle from whose wall the yolk; w, albumen, composed of alternating layers of membrana granulosa has partially more and less fluid portions; ch.l, chalaze; a.ch, air chamber separated; f, cavity of liquor follic- at the blunt end of the egg—simply a space between the uli; g, ovum surrounded by cell mass two layers of the shell membrane; 7.s.m, inner, s.m, outer constituting cumulus odphorus (Pier- layer of the shell membrane; s, shell. sol). Fic. 5.—Section of well-developed Graafian follicle Fic. 6.—Uterine tube and ovary with from human embryo (von Herff); the enclosed ovum mature Graafian follicle about ready to burst contains two nuclei. (Ribemont-Dessaignes). the Graafian follicle, within which the ovum is eccentrically located (Figs. 4 and 230). The cells of the Graafian follicle immediately surrounding the ovum form the corona radiaia (Fig. 1) when the ovum is set free. Io THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION Ovulation and Menstruation.— When the ovum is ripe, the Graafian follicle is large and contains fluid, probably under pressure. The ripe follicles form bud-like projections at the surface of the ovary (Fig. 6), and at these points the ovarian wall has become very thin. It is probable that normally the bursting of the Graafian follicle and the discharge of the ovum are periodic and associated with the phenomena of menstruation, as maintained by Fraenkel and Villemin. That ovulation or discharge of the ovum from the ovary may occur independently of the menstrual periods has been proven by the observations of Leopold and of Ravano. Also in young girls ovulation may precede the inception of men- struation and it may occur in women some time after the menopause. Ovum Follicle cells At birth, or shortly after, all of the ova are formed in the ovary of the female child. Hensen estimates that a normal human female may develop in each ovary 200 ripe ova. Most of the young ova, which may number 50,000, degenerate and never reach maturity. At ovulation but one ovum is normally ripened and dis- charged from the ovary. Several ova, however, may be produced in a single follicle in rare cases. Such multiple follicles have been observed in human ane and are of frequent occurrence in the ovary of the monkey (Fig. 7). The Spermatozoén.—The male cell or spermatozoén of man is a minute cell 0.055 mm. long, specialized for active movement. Because of their active move- THE GERM CELLS II ments, spermatozoa were, when first discovered, regarded as parasites living in the seminal fluid. The sperm cell is composed of a flattened head, short neck, and thread-like tai) (Fig. 8). The head is about 0.005 mm. in length. It appears oval in side view, pear-shaped in profile. When stained, the anterior two-thirds of the head may be seen to form a cap, and the sharp border of this cap is the perforatorium by means of which the spermatozoén penetrates the ovum. The head contains the nuclear elements of the sperm cell. The disc-shaped neck con- tains the anterior centrosomal body. The tail begins with the posterior centrosomal body and is divided into a short connecting piece, a chief piece or flagellum, which forms about four-fifths of the length of the sperm cell, and a short end piece, or terminal fila- ment. The connecting piece is marked off The connecting piece is traversed by the axial from the chief piece by the annulus. filament (filum principale), and is sur- rounded (1) by the sheath common to it and to the flagellum; (2) by a sheath con- taining a spiral filament; and (3) by a mitochondrial sheath. The chief piece is composed of the axial filament surrounded by a cytoplasmic sheath, while the end piece comprises the naked continuation of the axial filament. The spermatozoa are motile, being propelled by the movements of the tail. They swim always against a current at the rate of about 2.5 mm. a minute. Perforatorium Cap Head “Ant. centrosomal body Neck | E 1) Post. centrosomal body Spiral filament Sheath of axial filament «| Mitochondrial sheath Connect- ing piece of tail Annulus Axial filament Chief piece } H apie saat End piece of tail Fic. 8.—Diagram of a human spermat- ozoén, highly magnified, in side view (Meves, Bonnet). This is important, as the outwardly directed currents induced by the ciliary action of the uterine tubes and uterus direct the spermatozoa by the shortest route to the infundibulum. Keibel has found spermatozoa alive three days after the execution of the criminal from whom they were obtained. They have been found motile 12 THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION in the uterine tube three and one-half weeks after coitus. They have been kept alive eight days outside the body by artificial means. It is not known for how long a period they may be capable of fertilizing ova, but, according to Keibel, this period would certainly be more than a week. Lode estimates that 200 million spermatozoa are liberated at an average ejaculation. MITOSIS AND AMITOSIS Before the discharged ovum can be fertilized by the male germ cell, it must undergo a process of cell division and reduction of chromosomes known as matu- ration. As the student may oy a not be familiar with the proc- Sm ON i pas % esses of cell division, a brief description is appended. (For details of mitosis see text- books of histology and E. B. Wilson’s ‘The Cell.’’) Amitosis.—Cells may di- vide directly by the simple fission of their nuclei and cytoplasm. This rather in- frequent process is called amilosis. Amitosis is said by many to occur only in moribund cells. It is the type of cell division demon- strable in the epithelium of the bladder. Mitosis.—In the repro- duction of normally active cells, complicated changes take place in the nucleus. These changes give rise to Ny. Pia ae es, se oe thread-like structures, hence Fic. 9.—Diagram of the phases of mitosis (Schafer). the Process is termed mitosis (thread) in distinction to amitosis (no thread). Mitosis is divided for Convenience into four phases (Fig. 9). \ oa ( & i : ; wt é Se, MITOSIS AND AMITOSIS 13 Prophase.—1. The centrosome divides and the two minute bodies resulting from the division move apart, ultimately occupying positions at opposite poles of the nucleus (I-III). 2. Astral rays appear in the cytoplasm about each centriole. They radiate from it and the threads of the central or achromatic spindle are formed between the two asters, thus constituting the amphiaster (II). 3. The nuclear membrane and nucleolus disappear, the nucleoplasm and cytoplasm becoming continuous. 4. During the above changes the chromatic network of the resting nucleus resolves itself into a skein or spiveme, which soon shortens and breaks up into distinct, heavily-staining bodies, the chromosomes (II, III). A definite number of chromosomes is always found in the cells of a given species. The chromosomes may be block-shaped, rod-shaped, or bent in the form of a U. ° 5. The chromosomes arrange themselves in the equatorial plane of the central spindle (IV). If U-shaped, the base of each U is directed toward a common center. The amphiaster and the chromosomes together constitute a mitotic figure and at the end of the prophase this is called a monaster. Metaphase.—The longitudinal splitting of the chromosomes into exactly similar halves constitutes the metaphase (IV, V). The aim of mitosis is thus ac- complished, an accurate division of the chromatin between the nuclei of the daughter cells. Anaphase.—At this stage the two groups of daughter chromosomes separate and move up along the central spindle fibers, each toward one of the two asters. Hence this is called the diaster stage (V, VI). At this stage, the centrioles may each divide in preparation fot the next division of the daughter cells. Telophase.—1. The daughter chromosomes resolve themselves into a retic- ulum and daughter nuclei are formed (VII, VIII). 2. The cytoplasm divides in a plane perpendicular to the axis of the mitotic spindle (VIII). Two complete daughter cells have thus arisen from the mother cell. The complicated processes of mitosis, by which cell division is brought about normally, seem to serve the purpose of accurately dividing the chromatic sub- stance of the nucleus in such a way that the chromatin of each daughter cell may be the same qualitatively and quantitatively. This is important if we assume that the chromatic particles of the chromosomes bear the hereditary qualities of the cell. The number of chromosomes is constant in the sexual cells of a given species. The smallest number of chromosomes, two, occurs in Ascaris megalo- 14 THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION cephala univalens, a round worm parasitic in the intestine of the horse. The largest number known is found in the brine shrimp, Artemia, where 168 have been counted. The number for the human cell is in doubt. Guyer (1910) and Montgomery (1912) found 22 in the spermatogonia of negroes, and Guyer (1913) reported considerably larger numbers (count not given) for white spermatogonia. According to Winiwarter’s recent work on whites (Arch. de Biol., T. 27, 1912), the number of chromosomes in each immature ovum or odcyte is 48, in each spermatogone 47. Wieman (1913) found the most frequent number in various white somatic cells to be 34, but recently (Amer. Jour. Anat., vol. 21, 1917) he asserts that the number in both negro and white spermatogonia is 24, thereby agreeing with Duesberg (1906). We have seen that reproduction in mammals is dependent upon the union of male and female germ cells. The union of two germinal nuclei (pronuclei) would necessarily double the number of chromosomes in the fertilized ovum and also the number of hereditary qualities which their particles are supposed to bear. This multiplication of hereditary qualities is prevented by the processes of matu- vation which take place in both the ovum and spermatozoon. MATURATION Maturation may be defined as a process of cell division during which the number of chromosomes in the germ cells is reduced to one-half the number characteristic for the species. The spermatozoa take their origin in the germinal epithelium of the testis. Their development, or spermatogenesis, may be studied in the testis of man or of the rat; their maturation stages in the tubular testis of Ascaris. Two types of cells may be recognized in the germinal epithelium of the seminiferous tubules, the sustentacular cells (of Sertoli), and the male germ cells or spermatogonia (Fig. 10). The spermatogonia divide, one daughter cell forming what is known as a primary spermatocyte. The other daughter cell persists as a spermatogone, and, by continued division during the sexual life of the individual, gives rise to other primary spermatocytes. The primary spermatocytes correspond to the ova before maturation. Each contains the number of chromosomes typical for the male of the species. The process of maturation consists in two cell divisions of the primary spermatocytes, each producing first, two secondary spermatocytes, and these in turn four cells known as spermatids. During these cell divisions the number of chromosomes is reduced to half the original number, the spermatids possessing just half as many chromosomes as the spermatogonia. Each spermatid now becomes transformed into a mature spermatozoon (Fig. 11). The nucleus forms the larger part of the head; the centrosome divides, the resulting moieties passing to the extremities of the neck. The posterior centrosome is prolonged to MATURATION 15 Sp’c. IT (telophase) .___ No Sp’c. II (metaphase)___Aylf} fons. Wi Z. Primary spermatocyte Accessory chromo- , , Th Te A . Uf - some (?) SPevd Spnaplease) ENT] LO ~Sp’c. I (metaphase) -Sp’c. I (prophase) wall Nee Sp’g. (anaphase) Fic. 10.—Stages in the spermatogenesis of man arranged in a composite to represent a portion of a seminiferous tubule sectioned transversely. X 900. Cc Fic. 11.—Diagrams of the development of spermatozoa (after Meves in Lewis and Stthr). a.c., Anterior centrosome; a.f., axial filament; c.p., connecting piece; ch.p., chief piece; g.c., cap; n., nucleus; #%., neck; p., protoplasm; ?.c., posterior centrosome. form the axial filament, and the cytoplasm forms the sheaths of the neck and tail. The spiral filament of the connecting piece is derived from the cytoplasmic mito- chondria. 16 THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION The way in which the number of chromosomes is reduced may be seen in the spermatogenesis of Ascaris (Fig. 12). Four chromosomes are typical for Ascaris megalocephala bivalens and each spermatogone contains this number. In the early prophase of the primary spermatocyte there appears a spireme thread con- *«Q Fi: Fic. 12.—Reduction of chromosomes in the spermatogenesis of Ascaris megalocephala bivalens (Brauer, Wilson). XX about 1100. A-G, successive stages in the division of the primary spermatocyte. The original reticulum undergoes a very early division of the chromatin granules which then form a doubly split spireme (B, in profile). This becomes shorter (C, in profile) and then breaks in two to form two tetrads (D, in profile), (EZ, in end). F, G, H, first division to form two secondary spermato- cytes, each receiving two dyads. J, secondary spermatocyte. J, K, the same dividing. L, two resulting spermatids, each containing two single chromosomes. sisting of four parallel rows of granules (B). This thread breaks in two and forms two quadruple structures known as tetrads (D-F); each is equivalent to two original chromosomes split lengthwise to make a bundle of four. At the meta- phase (G) the two fetrads split each into two chromosomes which already show evidence of longitudinal fission and are termed dyads. One pair of dyads goes to MATURATION 17 each of the daughter cells, or secondary spermatocytes (G-I). Without the formation of a nuclear membrane, the second maturation spindle appears at once, the two dyads split into four monads, and each daughter spermatid receives two single chromosomes, or one-half the number characteristic for the species. The tetrad, therefore, represents a precocious division of the chromosomes in prepara- tion for two rapidly succeeding cell divisions which occur without the intervention of the customary resting periods. The easily understood tetrads are not formed in most animals, although the outcome of maturation is identical in either case. A diagram of maturation is shown in Fig. 13. The first maturation division in Ascaris is probably reductional, each daughter nucleus receiving two complete A B Spermatogonium Odgonium Proliferation period Growth . iod Spermatocyte 1 Odcyte x pane Odcyte 2 (ovum Spermatocyte 2 and polocyte r) Maturation é period : vum and Spermatids three polo- J cytes Transforma- Spermatozoa tion period of 1 2 3 4 1 2 3 4 Spermatozoa Fic. 13.—Diagrams of maturation, spermatogenesis and odgenesis (Boveri). chromosomes of the original four, whereas in the second maturation division, as in ordinary mitosis, each daughter nucleus receives a half of each of the two chromo- somes, these being split lengthwise. In the latter case the division is equational, each daughter nucleus reciving chromosomes bearing similar hereditary qualities. In some animals the sequence of events is reversed, reduction occurring at the second maturation division. In many insects and some vertebrates it has been shown that the number of chromosomes in the oégonia is even, the number in the spermatogonia odd, and that all the mature ova and half the spermatids contain an extra or accessory chromosome (see p. 32). During odgenesis, the ova undergo a similar process of maturation. Two 2 18 THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION cell divisions take place but with this difference, that the cleavage is unequal, and, instead of four cells of equal size resulting, there are formed one large ripe ovum or odcyte and three rudimentary or abortive ova known as polar bodies or polocytes. The number of chromosomes is reduced in the same manner as in the spermatocyte, so that the ripe ovum and each polar cell contain one-half the number of chromosomes found in the immature ovum or primary odcyte. The female germ cells, from which new ova are produced by cell division, are called odgonia and their daughter cells after a period of growth within the ovary are the primary odcytes, comparable to the primary spermatocytes of the male (Fig. 12). During maturation the ovum and first polocyte are termed secondary odcytes (comparable to secondary spermatocytes), the mature ovum and second polocyte, with the daughter cells of the first polocyte, are comparable to the | spermatids. Each spermatid, however, may form a mature spermatozoén, but only one of the four daughter cells of the primary odcyte becomes a mature ovum. The ovum develops at the expense of the three polocytes which are abortive and degenerate eventually, though it has been shown that in the ova of some insects the polar cell may be fertilized and segment several times like a normal ovum. In most animals, the actual division of the first polocyte into two daughter cells is suppressed. The maturation of human ova has not been observed, but such a process undoubtedly takes place. The reduction of the chromosomes may be best observed in the germ cells of Ascaris and of insects. The mouse offers a favorable opportunity for studying the maturation of a mammalian egg as the ova are easily obtained. Their maturation stages have recently been studied by Long and Mark (Carnegie Inst. Publ. No. 142). Maturation of the Mouse Ovum.—The nucleus of the ovum after maturation is known as the female pronucleus. When the spermatozoon penetrates the mature ovum it loses its tail, and its head becomes the male pronucleus. The aim and end of fertilization consists in the union of the chromatic elements contained in the male and female pronuclei and the initiation of cell division. In the mouse, the first polocyte is formed while the ovum is still in the Graafian follicle. In the formation of the maturation spindle no astral rays and no typical centrosomes have been observed. The chromosomes are V-shaped. The first polar cell is constricted from the ovum and lies beneath the zona pellucida as a spherical mass about 25 micra in diameter (Fig. 14). Both ovum and polar cell (secondary oécytes) contain 20 chromosomes, or half the number normal for the mouse. The first maturation division is the reductional one and the chromosomes take the form of tetrads. FERTILIZATION Ig After ovulation has taken place, the ovum lies in the ampulla of the uterine tube. If fertilization occurs, a second polocyte is cut off, the nucleus of the ovum forming no membrane between the production of the first and second polar bodies (Fig. 14 A-D). The second maturation spindle and second polar cell are Fic. 14.—Maturation and fertilization of the ovum of the mouse (after Sobotta). A, C-J, X 500; BX 750. A-—D, entrance of the spermatozoén and formation of the polar cells. D-—E, development of the pronuclei. F—J, successive stages in the first division of the fertilized ovum. smaller than the first. Immediately after the formation of the second polar cell, the chromosomes resolve themselves into a reticulum and the female pronucleus is formed (Fig. 14 D). FERTILIZATION Fertilization of the Mouse Ovum.—Normally, a single spermatozoén enters the ovum six to ten hours after coitus. While the second polar cell is forming, 20 THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION the spermatozoén penetrates the ovum and loses its tail. Its head is converted into the male pronucleus (Fig. 14D). The pronuclei, male and female, approach each other and resolve themselves first into a spireme stage, then into two groups of 20 chromosomes. A centrosome, possibly that of the male cell, appears be- tween them, divides into two, and soon the first segmentation spindle is formed (F-H). The 20 male and 20 female chromosomes arrange themselves in the equatorial plane of the spindle, thus making the original number of 40 (J). Fer- ‘tilization is now complete and the ovum divides in the ordinary way, the daughter cells each receiving equal numbers of maternal and paternal chromosomes. The fundamental results of the process of fertilization are: (1) the wnion of the male and female chromosomes to form the cleavage nucleus of the fertilized ovum, (2) the initiation of cell division or cleavage of the ovum. These two factors are separate and independent phenomena. It has been shown by Boveri and others that fragments of sea urchin’s ova containing no part of the nucleus may be fertilized by spermatozoa, segment, and develop into larve. The female chromosomes are thus not essential to the process of segmentation. Loeb, on the other hand, has shown that the ova of invertebrates may be made to develop by chemical and mechanical means without the codperation of the spermatozoon (artificial parthenogenesis). Even adult frogs have been reared from mechanically stimulated eggs. It is well known that the ova of certain inver- tebrates develop normally without fertilization, that is, parthenogenetically. These facts show that the union of the male and female pronuclei is not the means of initiating the development of the ova. In all vertebrates it is, nevertheless, the end and aim of fertiliza- tion. Lillie (Science, vols. 36 and 38; 1912, 1913) has recently shown that the cortex of sea urchin’s ova produces a substance which he terms fertilizin. This substance he regards as an amboceptor essential to fertilization, with one side chain which agglutinates and attracts the spermatozoa, and another side chain which activates the cytoplasm and initiates the cleavage of the ovum. According to Loeb, the spermatozoén activates the ovum to develop by in- creasing its oxidations and by rendering it immune to the toxic effects of oxidation. Spermatozoa may enter the mammalian ovum at any point. If fertilization is delayed and too long a period elapses after ovulation, the ovum may be weak- ened and allow the entrance of several spermatozoa. This is known as polvy- spermy. In such cases, however, only one spermatozo6n unites with the female pronucleus. Fertilization of the Human Ovum.—This has not been observed, but prob- ably takes place in the uterine tube some hours after coitus. Ova may be fertil- ized and start developing before they enter the uterine tube. If they attach them- selves to the peritoneum of the abdominal cavity, they give rise to abdominal pregnancies. If the ova develop within the uterine tube ‘wbal pregnancies result. Ovarian pregnancies are known also. Normally, the embryo begins its develop- FERTILIZATION 21 ment in the uterine tube, thence passes into the uterus and becomes embedded in the uterine mucosa. The time required for the passage of the ovum from the uterine tube to the uterus is unknown. It probably varies in different cases and may occupy a week or more. The ovum may in some cases be fertilized within the uterus. Fertilization is favored by the fact that the spermatozoa swim always against a current. As the cilia of the uterus and uterine tube beat downward and outward the sperms are directed upward and inward. They may reach the ova- rian ends of the uterine tubes within two hours of a normal coitus. Twin Development.—Usually but one human ovum is produced and fertilized at coitus. The development of two or more embryos within the uterus is commonly due to the ripening, expulsion, and subsequent fertilization of an equal number of ova. In such cases ordinary or fraternal twins, triplets, and so on, of the same or opposite sex, result. Identical twins, that is, those always of the same sex and strikingly similar in form and ‘feature, are regarded as arising from the daughter cells of a fertilized ovum, these having separated and each having developed like a normal ovum. Separate development of the cleavage cells can be produced experimentally in many of the lower animals. The offspring of the armadillo are normally produced in this manner (Patterson). The Significance of Mitosis, Maturation and Fertilization.—It is assumed by students of heredity that the chromatic particles of the nucleus bear the hereditary qualities of the cell. During the course of development these particles are probably distributed to the various cells in a definite way by the process of mitosis. The process of fertilization would double the number of hereditary qualities and they would be multiplied indefinitely were it not for maturation. At maturation not only is the number of chromosomes halved, but it is assumed also that the number of hereditary qualities is reduced by half. In the case of the ovum, maturation takes place at the expense of three potential ova, the polocytes, which de- generate, but to the advantage of the single mature ovum which retains more than its share of cytoplasm and nutritive yolk. Mendel’s Law of Heredity.—Experiments show that most hereditary characters fall into two opposing groups, the contrasted pairs of which are termed allelomorphs. As an example, we may take the hereditary tendencies for black and blue eyes. It is supposed that there are paired chromatic particles which are responsible for these hereditary tendencies, and that paired spermatogonial chromosomes bear one each of these particles. Each chro- mosome pair in separate germ cells may possess similar particles, both bearing black-eyed tendencies or both blue-eyed tendencies, or opposing particles, bearing the one black, the other blue-eyed tendencies. It is assumed that at maturation these paired particles are separated along with the chromosomes, and that one only of each pair is retained in each germ cell, in order that new and favorable combinations may be formed at fertilization. In our example, either a blue-eyed or a black-eyed tendency bearing particle would be retained. At fertilization the segregated tendency-bearing particles of one sex may enter into new combina- tions with their allelomorphs from the other sex, combinations which may be favorable to the offspring. Three combinations are possible. If the color of the eyes be taken as the hereditary character, (1) two ‘“‘black” germ celis may unite; (2) two “‘blue” germ cells may unite; (3) a “black” germ cell may unite with a “blue” germ cell. The offspring in (1) will all have black eyes, and, if interbred, their progeny will likewise inherit black eyes exclusively. Similarly, the offspring in (2), and if these are interbred their progeny as well, will include 22 THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION nothing but blue-eyed individuals. The first generation from the cross in (3) will have black eyes solely, for black in the present example is dominant, as it is termed. Such black-eyed individuals, nevertheless, possess blue-eyed bearing chromatic particles in their germ cells; in the progeny resulting from the interbreeding of this class the original condition is repeated —pure blacks, impure blacks which hold blue recessive, and pure blues will be formed in the ratio of 1: 3:1 respectively. It is thus seen that blue-eyed children may be born of black- eyed parents, whereas blue-eyed parents can never have black-eyed offspring. Many such allelomor phic pairs of unit characters are known. DETERMINATION OF SEX The assumption that the chromosomes are the carriers of hereditary ten- dencies is borne out by the observations of cytologists on the germ cells of inver- tebrates, especially insects, and of some vertebrates. According to Winiwarter (Arch. de Biol., T. 27, 1912) the nuclei of human spermatogonia contain 47 chro- mosomes, while those of the odgonia contain 48. When maturation and reduction of the chromosomes take place in the male cells, one unpaired chromosome fails to divide and passes intact to one or the other daughter cells; hence half of the spermatids contain 24 chromosomes, the other half only 23. All the odcytes and polocytes, on the contrary, contain 24. There is thus one extra chromosome in each mature ovum and in each of half the spermatozoa. This chromosome, because of peculiarities of size or shape, can be identified easily m many animals, and is termed the accessory chromosome. McClung was the first to assume that the accessory chromosome is a sex determinant. It has since been shown by Wilson, Davis, and others that the accessory chromosome carries the female sexual characters. When, in the case under consideration, a spermatozoan with 24 chromosomes fertilizes an ovum, the resulting embryo is a female, its somatic nuclei containing 48 chromosomes. An ovum fertilized by a sperm cell containing only 23 chromosomes (without the accessory chromosome) produces a male with 2 somatic nuclei containing only 47 chromosomes. These ob “ons of Wini- warter on man have yet to be confirmed by otLer investigators. 1t 1s probable, however, that sex is transmitted by the human chromosomes essentially in the manner described, which agrees with the easily observed phenomena in insects. CHAPTER II CLEAVAGE OF THE FERTILIZED OVUM AND ORIGIN OF THE GERM LAYERS CLEAVAGE THE processes of cleavage, or segmentation, not having been observed in human ova, must be studied in other vertebrates. It is probable that the early development of all vertebrates is, in its essentials, the same. Cleavage may be modified, however, by the presence in the ovum of large quantities of nutritive yolk. In many vertebrate ova the yolk collects at one end, termed the vegetal pole, in contrast to the more purely protoplasmic animal pole. Such ova are said to be telolecithal. Examples are the ova of fishes, amphibians, reptiles, and birds. When very little yolk is present, the ovum is said to be isolecithal. Examples are the ova of Amphioxus, the higher mammals, and man. The typical processes of cleavage may be studied most easily in the fertilized ova of invertebrates (Echinoderms, Annelids, and Mollusks). Among Chordates, the early processes in development are primitive in a fish-like form Amphioxus. The yolk modifies the development of the amphibian and bird egg, while the early structure of the mammalian embryo can be explained only by assuming that the ova of the higher Mammalia at one time contained a considerable amount of yolk, like the ovum of the bird and of the lower mammals, and the influence of this condition persists. Cleavage in, ‘.nphioxus.—The ovum is essentially isolecithal since it contains but little yolk (Lig. 15). About one hour after fertilization it divides vertically into two nearly equal daughter cells, or blastomeres. The process is known as cell cleavage, or segmentation, and takes place by mitosis. Within the next hour the daughter cells again cleave in the vertical plane, at right angles to the first division, thus forming four cells. Fifteen minutes later a third division takes place in a horizontal plane. As the yolk is somewhat more abundant at the vege- tal pole of the four cells cne mitotic spindles lie nearer the animal pole. Conse-, quently in the eight-celled stage the upper tier of four cells is smaller than the lower four. By successive cleavages, first in the vertical, th. 1 in the horizontal plane a 16- and 32-celled embryo is formed. The upper two tiers are now smaller, 23 24 CLEAVAGE AND THE GERM LAYERS and a cavity, the blastocele, is enclosed by the cells. The embryo at this stage is sometimes called a morula (mulberry). In subsequent cleavages, as development proceeds, the size of the cells is diminished while the cavity enlarges (Fig. 15). Fic. 15.—Cleavage of the egg of Amphioxus (after Hatschek). 200. 1. The egg before the commencement of development; only one polar body, P.B., is present, the other having been lost during ovulation. 2. The ovum in the act of dividing, by a vertical cleft, into two equal blastomeres. 3. Stage with four equal blastomeres. 4. Stage with eight blastomeres; an upper tier of four slightly smaller ones and a lower tier of four slightly larger ones.’ 5. Stage with sixteen blastomeres in two tiers, each of eight. 6. Stage with thirty-two blastomeres, in four tiers, each of eight; the embryo is represented bisected to show the cleavage cavity or blastoccele, B. 7. Later stage; the blastomeres have increased in number by further division. 8. Blastula stage bisected to show the blastoccele, B. The embryo is now a blastula, nearly spherical in form and about four hours old. The cleavage of the Amphioxus ovum is thus holoblastic, i. e., complete, and nearly equal. CLEAVAGE 25 Cleavage in Amphibia—These ova contain so much yolk that the nucleus and most of the cytoplasm lies at the upper or animal pole. The first cleavage spindle lies in this cytoplasm. ‘The first two cleavage planes are vertical and at Fic. 16.—Cleavage of the frog’s ovum (Hatschek in Marshall). X 20. B, Blastoceele or cleavage cav- ity; NV, nucleus. right angles, and the four resulting cells are nearly equal (Fig. 16,1). The spindles for the third cleavage are located near the animal pole and the cleavage takes place in a horizontal plane. As a result, the upper four cells are much srhaller than the lower four (2 and 3). The large yolk-laden cells divide more 26 CLEAVAGE AND THE GERM LAYERS slowly than the upper small cells. At the blastula stage, the cavity is small, and the cells of the vegetal pole are each many times larger than those at the animal pole (4 and 5). The cleavage of the frog’s ovum is thus complete but unequal. Cleavage in Reptiles and Birds.—The ova of these vertebrates contain a large amount of yolk. There is very little pure cytoplasm except at the animal pole and here the nucleus is located (Fig. 3). When segmentation begins, the first cleavage plane is vertical but the inert yolk does not cleave. The segmen- tation is thus incomplete or meroblastic. In the hen’s ovum the cytoplasm is divided by successive vertical furrows into a mosaic of cells, which, as it increases in size, forms a cap-like structure upon the surface of the yolk. These cells are separated from the yolk beneath by horizontal cleavage furrows, and successive horizontal cleavages give rise to several layers of cells. The space between cells and yolk mass may be compared to the blastula cavity of Amphioxus and the frog (Fig. 18). The cellular disc or cap is termed the germinal disc or blasto- derm. The yolk mass, which forms the floor of the blastula cavity and the greater part of the ovum, may be compared to the large yolk-laden cells at the vegetal pole of the frog’s blastula. The yolk mass never divides but is gradually used up in supplying nutriment to the embryo which is developed from the cells of the germinal disc. At the periphery of the germinal disc new cells constantly form until they enclose the yolk. Cleavage in Mammals.—The ovum of all the higher mammals, like that of man, is isolecithal and nearly microscopic in size. Its cleavage has been studied in several mammals but the rabbit’s ovum will serve as an example. The cleav- age is complete and nearly equal (Fig. 17), a cluster of approximately uniform cells being formed within the zona pellucida. This corresponds to the morula stage of Amphioxus. Next an inner mass of cells is formed which is equivalent to the germinal disc, or blastoderm, of the chick embryo (Fig. 17). The inner cell mass is overgrown by an outer layer which is termed the troplecioderm, because, in mammals, it later supplies nutriment to the embryo from the uterine wall. Fluid next appears between the outer layer and the inner cell mass, thereby sepa- rating the two except at the animal pole. As the fluid increases in amount, a hol- low vesicle results, its walls composed of the single-layered trophectoderm except where this is in contact with the inner cell mass. This stage is known as that of the blastodermic vesicle. It is usually spherical or ovoid in form, as in the rabbit, and probably this is the form of the human ovum at this stage. In the rabbit the vesicle is 4.5 mm. long before it becomes embedded in the wall of the uterus. Outer cell. Outer cetts. Zona pellucida Outer cell- DHASS, Polar bodies Inner cell- MASS. Inner cell Outer cells. Inner cells. Inner cells. Outer cells Inner cells. Tebheckede< n Cua, G t(, \nnev Cell macs Outer cedls. Fic. 17—Diagrams showing the cleavage of the mammalian (rabbit’s) ovum and the formation of the blastodermic vesicle (Allen Thomson, after van Beneden). X 200. CLEAVAGE a Among Ungulates (hoofed animals) the vesicle is greatly elongated and attains a length of several centimeters, as in the pig. If we compare the mammalian blastodermic vesicle with the blastula stages of Amphioxus, the frog, and the bird, it will be seen that it is to be homologized with the bird’s blastula, not with that of Amphioxus (Fig. 18). In each case there is an inner cell mass of the germinal disc. The trophectoderm of the mammal represents a precocious development of cells, which, in the bird, later envelop the yolk. The cavity of the vesicle is to be compared, not with the Frc. 18.—Diagrams showing the blastule: A, of Amphioxus; B, of frog; C, of chick; D, blastodermic vesicle of mammal. blastula cavity of Amphioxus and the frog, but with the yolk mass plus the rudi- mentary blastocele of the bird’s ovum. The mammalian ovum, although almost Evol alk, thus develops much like the yolk-laden ova of reptiles and birds. This similarity has an evolutionary significance. Its cleavage, however, is complete and the early stages in its development are abbreviated. In Primates, but one cleavage stage has been observed. This, a four-celled ovum of Macacus nemestrinus figured by Selenka, shows the cells nearly equal and oval in form. This ovum was found in the uterine tube of the monkey and shows that, in Primates and prob- ably in man, cleavage as in other mammals takes place normally in the oviducts. 28 CLEAVAGE AND THE GERM LAYERS THE FORMATION OF THE ECTODERM AND ENTODERM (GASTRULATION) The blastula and early blastodermic vesicle show no differentiation into layers. Such differentiation takes place later in all vertebrate embryos, giving tise first to the ectoderm and entoderm, and finally to the mesoderm. From these three primary germ layers all tissues and organs of the body are derived. The processes of gastrulation, by which ectoderm and entoderm arise, and of mesoderm formation will be treated separately. Amphioxus and Amphibia.—In these animals the larger cells at the vegetal pole of the blastula either fold inward, i. e., invaginate (Amphioxus, Fig. 19), or are for the most part overgrown by the more rapidly dividing cells of the animal Fic. 19.—Gastrulation of amphioxus (Hatschek in Heisler). 220. A, Blastula: a, animal cells; v, vegetative cells; c.c., cleavage cavity. B, Beginning invagination of vegetative pole. C, Gastrula, the invagination of the vegetative cells being complete: ect., ectoderm; ent., entoderm; arch., archenteron; bl, blastopore. pole (amphibia). Eventually the invaginating cells obliterate the blastula cavity and come in contact with the outer layer of cells (Fig. 19). The new cavity thus formed is the primitive gut or archenteron and its narrowed mouth is the blastopore. The outer layer of cells is the ectoderm, the inner, newly formed layer is the ento- derm. The entodermal cells are henceforth concerned in the nutrition and metab- olism of the body. The embryo is now termed a Gastrula (little stomach). Reptiles and Birds.—The germinal disc, or blastoderm, in these animals lies like a cap on the surface of inert yolk (Fig. 3). Since the enormous amount of yolk makes gastrulation as in Amphioxus and amphibians impossible, the process exhibits marked modifications. ORIGIN OF THE MESODERM, NOTOCHORD AND NEURAL TUBE 29 There appears caudally on the blastoderm of reptiles a pit-like depression. From this slight invagination a proliferation of cells forms a layer which spreads beneath the ectoderm (cf. Fig. 21.4). The inner layer originating in this manner is the entoderm, and the region of the pit where ectoderm and entoderm are con- tinuous is the blastopore. In birds the caudal portion of the blastoderm is rolled or tucked under, the inner layer formed in this way constituting the entoderm. The marginal region where ectoderm and entoderm meet bounds the dlastopore, while the space be- tween entoderm and yolk is the archenteron._ ~~ Mammals.—As in cleavage, so also in gastrulation the mammalian ovum exhibits a modified behavior indicative of an ancestral yolk-rich condition. The entoderm apparently arises by a splitting off, or delamination, of cells from the under side of the inner cell mass (Figs. 16,74 A and 75). In the blastoderm of the rabbit, opossum, and mole, however, a minute pore has been observed at which the ectoderm and entoderm are continuous. This opening is believed by some to represent a true blastopore where the ingrowth of entodermal cells has occurred. ORIGIN OF THE MESODERM, NOTOCHORD AND NEURAL ‘TUBE Amphioxus and Amphibia.—The dorsal plate of entoderm, which forms the roof of the archenteron in Amphioxus, gives rise to paired lateral diverticula or celomic pouches (Fig. 20). These separate both from the plate of cells in the mid- Fic. 20.—Origin of the mesoderm in Amphioxus (after Hatschek). XX about 425. x.g., Neural groove; m.c., neural canal; ch., anlage of notochord; mes. som., mesodermal segment; ect., ectoderm; ent., entoderm; al., cavity of gut; cw., coelom or body cavity. dorsal line (which forms the notochord), and from the entoderm of the gut, and become the primary mesoderm. ‘The mesodermal pouches grow ventral and their cavities form the celom'or body cavity. Their outer walls, with the ectoderm, 30 CLEAVAGE AND THE GERM LAYERS form the body wall or somatopleure ; their inner walls, with the gut entoderm, form the intestinal wall or splanchnopleure. In the meantime, a dorsal plate of cells, cut: off from the ectoderm, has formed the neural tube (anlage of the nervous system), and the notochordal plate has become a cord or cylinder of cells (axial skeleton) extending the length of the embryo. In this simple fashion the ground plan of the chordate body is developed. In Amphibia the mesodermal diverticula grow out from the dorsal entoderm as solid plates between the ectoderm and entoderm. Later, these plates spht into two layers and the cavity so formed gives rise to the coelom. Ectoderm TB iol PO MOS HOLS FICCI PRS Hea I 7 GIMVAPA aos Siitoinraconace elo ale arstarerath Mat i WN vir bP LT Tarn LR 2 RRR = Palais rena — I SENDS #0 CSRS Entoderm Notochordal x plate Remnant of floor Fic. 21.—Longitudinal sections of the snake’s blastoderm at various stages to show the oxic of the notochordal plate (adapted after Hertwig). Reptiles.—The same pocket-like depression in the caudal portion of the blastoderm, which gave rise to the cells of the entodermal layer, now invaginates more extensively and forms a pouch which pushes in between ectoderm and ento- derm (Fig. 21 A and B). The size of the invagination cavity varies in different species; in some it is elongated and narrow, being confined to the middle line of the blastoderm. ‘The floor of this pouch soon fuses with the underlying entoderm and the two thin, rupture, and disappear, thus putting the cavity of the pouch in ORIGIN OF THE MESODERM, NOTOCHORD AND NEURAL TUBE 31 communication with the space (archenteron) beneath the entoderm (Fig. 21 C). The cells of the roof persist as the notochordal plate which later gives rise to the notochord. The neural folds arise before the mouth of the pouch (blastopore) closes up, and, fusing to form the neural tube, incorporate the blastopore in its floor. This temporary communication between the neural tube and the primitive enteric cavity is the neurenteric canal (Fig. Di C); it is found in al the vertebrate groups (cf. Fig. 78). A transverse section through the invaginated pouch, at the time of rupture of its floor, and the underlying entoderm will make clear the rela- tively slight lateral extent of these changes (Fig. 22). From about the blastopore, and from the walls of the pouch, mesodermal plates arise and extend like wings between the ectoderm and entoderm (Fig. 22). As in amphibia they later separate into outer (somatic) and inner (splanchnic) layers enclosing the coelom (cf. Fig. 29 B). The relation between notochordal plate, mesoderm, and entoderm shown in Fig. 22 resembles strikingly the condi- tions in Amphioxus (Fig. 20 A). Ectoderm Mesoderm atarCTeele Notochordal Entoderm Pitrare ; plate Fic. 22,—Transverse section of a snake’s blastoderm at a level corresponding to the middle of Fig. 21 C (adapted after Hertwig). Birds.—Due to the modified gastrulation in reptiles, birds, and mammals through the influence of yolk, a structure known as the primitive streak ee important. ‘An account of its formation and significance based on conditions found in the bird may be introduced conveniently at this place. Shortly after the formation of entoderm there appears in the median line at the more caudal portion of the blastoderm an elongated opaque band (Fig. 23). Along this primitive streak there forms a shallow primitive groove, bounded later- ally by primitive folds. Cranially the groove ends in a depression, the primitive pit. In front of this pit the streak ends in a knob, the primitive knot (of Hensen). The primitive streak becomes highly significant when interpreted in the light of the theory of concrescence, a theory of general application in vertebrate development. It will be remembered that the entode i ises_by a rolling under of the outer ng the caudal margi . As the blastoderm expands it is believed that a middle point on this margin remains 32 CLEAVAGE AND THE GERM LAYERS fixed while the edges of the margin on each side are carried caudad and brought together. Thus a crescentic margin is transformed into a longitudinal slit as in Fig. 24. Since this marginal lip originally bounded the blastopore (p. 29) the longitudinal slit must also be an elongated blastopore whose direction has merely been changed. The lips of the slit fuse, forming the primitive streak. The primi- tive groove may be interpreted as a further j __. Area opaca | bese futile attempt at invagination in the region tive k . Erimitz ot of the blastopore. The teachings of com- Primitive fold Patative embryology support these con- MW Primitive enue clusions, for the neurenteric canal arises at the cranial end of the primitive streak, ] Area pellucida ane | the anus at its caudal end, while the fe ‘ Blood island primary germ layers fuse in its substance. All these relations exist at the blastopore Fic. 23.—Blastoderm of a chick embryo of the lower animals. at the stage of the primitive streak and Hiei the thickened e@odenn ot the groove (16 hours). X 20. primitive streak a proliferation of cells takes place and there grows out laterally and caudally between the ectoderm and entoderm a solid plate of mesoderm (Fig. 31 Band C). From the primitive knot _a mesode mesodermal sheet also extends cephalad forming along the midline-a thicker “ayer: the er, the so-called head process or notochordal plate, which fuses intimately with the entoderm (Figs. 25, 30 and 31 A). eee Since the primitive streak and groove = é je represent a modified blastopore, it is no, aw fig SN evident that this cranial extension, the {|} ie A Wk AW head process, corresponds to the pouch- — a = SEY like invagination concerned in the forma- Fic. 24.—Diagram elucidating the forma- tion of the primitive streak (Duval in Heisler). The increasing size of the germ disc in the tiles. In birds the fusion of the head course of the development is indicated by dot- ted circular lines. The heavy lines represent the crescentic groove and the primitive streak of mesodermal sheets to it laterally, the which arises from it by the fusion of the edges of the crescent. tion of mesoderm and notochord in rep- process with the entoderm, the relation tormation of the notochord from its tis- sue, and the occasional traces in it of a cavity continuous with the primitive pit (i. e., neurenteric canal), all recall the conditions described for the less modified invagination in reptiles. Mammals.—On the blastoderm of mammals appear a primitive streak and ORIGIN OF THE MESODERM, NOTOCHORD AND NEURAL TUBE 33 knot essentially as in birds (Figs. 26 A and 28). Similarly from the keel-like ectodermal thickening of the primitive streak, mesoderm grows out laterally and caudally, and from the primitive knot it is continued cranially as the head process. ell epee ne oe Ma eat oD All three primary germ layers fuse in the primitive streak and knot, this condition Neural plate Primitive knot Head fold ; Primitive pit Primitive streak Ectoderm Ecto-. derm Head process Entoderm Mesoderm Yolk Fic. 25.—Median longitudinal section of a chick embryo at the stage of the primitive streak and head process. X 100. being known in man. The head process of many mammalian embryos contains a cavity (xotochordal canal), which in some cases is of considerable size, opening at the primitive pit. As in reptiles, the floor of this cavity fuses with the entoderm and the two rupture and disappear. A still persistent portion of the floor is shown in Fig. 27. Thus a neurenteric B canal, later enclosed by the neural folds, puts the dorsal surface of the blastoderm into communication with the enteric cavity beneath the entoderm (Figs. 77 and 78). The roof of the head process or notochordal canal is for a time continuous with the mesoderm and ento- derm (compare these relations in reptiles, Fig. 22), but it event- ually becomes the notochord. y Fic. 26.—The primitive streak of pig embryos (Kei- The extent of mesoderm bel). X 20. A, Embryo with primitive streak and prim- in rabbit embryos is shown in itive knot; B, a later embryo in which the neural groove is also present, cephalad in position. Fig. 28. Cranial to the primi- tive node the notochord is differentiated in the midline, the mesoderm being divided into two wings. The mesoderm rapidly grows around the wall of the blastodermic vesicle until it finally surrounds it and the two wings fuse ven- trally (Fig. 29). The single sheet of mesoderm soon splits into two layers, the cavity between being the celom_or body cavity. The outer mesodermal layer (somatic), with the ectoderm, forms the somatopleure or body wall, the inner 3 34 CLEAVAGE AND THE GERM LAYERS splanchnic layer, with the entoderm, forms the intestinal wall or Splanchnopleure. The neural tube having in the meantime arisen from the neural folds of the ecto- derm, there is present the ground plan of the vertebrate body, the same in man as in Amphioxus. No stages of gastrulation or mesoderm formation have yet been observed in the human embryo, but the primitive streak may be recognized in later stages Post. opening of notochordal canal Primitive streak Ant. opening of notochordal canal Ant. persisting portion of 7 Seah, notochordal canal Neurenteric canal Fic. 27.—Median longitudinal section through the blastoderm of a bat (Vespertilio murinus) (after Van Beneden). (Fig. 77), and there is evidence also of an opening, the neurenteric canal, leading from the exterior into the cavity of the primitive gut (archenteron). In Tarsius, an animal classed by Hubrecht,with the primates, the mesoderm has two sources: (1) From the splitting of ectoderm at the caudal edge of the blastoderm; this forms bate a Fic. 28.—Diagrams showing the extent of the mesoderm in rabbit embryos (Kolliker). In A the mesoderm is represented by the pear-shaped area about the primitive streak at the caudal end of the embryonic disc; in B, by the circular area which surrounds the embryonic disc. the extra-embryonic mesoderm and takes no part in forming the body of the embryo. (2) The intra-embryonic mesoderm, which gives rise to body tissues, takes its origin from the primitive streak and knot as in the chick and lower mammals. The origin of mesoderm in the human embryo is probably much the same as in Tarsius. ORIGIN OF THE MESODERM, NOTOCHORD AND NEURAL TUBE 35 The Notochord or Chorda Dorsalis.—Unlike in Amphioxus anu amphibia, the head (notochordal) process and mesoderm of higher vertebrates are not clearly of entodermal origin, but are derived from the ectoderm, any union with the entoderm being secondary. As the primitive streak recedes caudalward during development the head process is progressively lengthened at the expense of the former. UIti- mately the primitive streak becomes restricted to the tail region, whereas the entire remainder of the body is built up around the head process as an axis. In later Mesodermal segment Neural tube __ Ectoderm. Nephrotome Somatic Notochord Splanchnic mesoderm Fic. 29.—Diagrams showing the origin of the germ layers of mammals as seen in transverse section (modified from Bryce). stages, the rod-like notochord extends in the midline beneath the neural tube from the tail to a dorsal out-pocketing of the oral entoderm, known as Seessel’s pocket (p. 81). It becomes enclosed in the centra of the vertebrz and in the base of the cranium, and eventually degenerates. In Amphioxus it forms the only axial skeleton and it is persistent in the axial skeleton of fishes and amphibians. In man, traces of it are found as pulpy masses (nuclei pulpost) in the intervertebral discs. CHAPTER III THE STUDY OF CHICK EMBRYOS Cuick embryos may be studied whole and most of the structures identified up to the end of the second day. The eggs should be opened in normal saline solution at 40° C. With scissors cut around the germinal disc, float the embryo off the yolk, and remove the vitelline membrane. ‘Then float the embryo dorsal side up on a glass slide, remove enough of the saline solution to straighten wrinkles, and carefully place over the embryo a circle of tissue paper with opening large enough to leave the germinal disc exposed. Add a few drops of fixative (5 per cent. nitric acid gives good fixation) and float embryo into a covered dish. After fix- ing and hardening, stain in Conklin’s acid hematoxylin or in acid carmine. Extract sur- plus stain, clear, and mount on slide supporting cover-slip to prevent crushing the embryo. Acid hematoxylin gives the best results for embryos of the first two days. For a detailed account of embryological technique see Lee’s ““Microtomist’s Vade Mecum.”’ In the following descriptions we shall use the terms dorsad and ventrad to indicate “toward the back” or ‘toward the belly”; cephalad and craniad to denote ‘‘headward’’; caudad to denote “‘tailward’’; /aterad to indicate “toward the side”; and mesad, “toward the middle line.” EMBRYOS OF ABOUT TWENTY HOURS’ INCUBATION The events of cleavage and the formation of the primary germ layers in birds have been described in an earlier chapter. The appearance on the disc- like blastoderm (Fig. 3) of the primitive streak and groove (Fig. 23), and of its cranial extension, the head process (Fig. 25), has likewise received brief treatment (p. 31). In a chick embryo of twenty hours’ incubation (Fig. 30) the primitive streak is formed as a linear opacity near the posterior border of the germinal disc. Over a somewhat pear-shaped clear area the yolk has been dissolved*away from the overlying entoderm. This area, from its appearance, is termed the area pellucida. It is surrounded by the darker and more granular area opaca. Whether or not the primitive streak represents the fused lips of the blastopore, it is certain that it represents the point of origin for the middle germ layer, the extent of which is indicated by the shaded area of Fig. 30. It also indicates the future longitudinal axis of the embryo. The mesoderm extends at first more rapidly caudal to the primitive streak, at the cranial end of which appears a shaded _thickenin the primitive knot or node (of Hensen). From the primitive knot it grows cranially, forming along the midline a thicker layer of tissue, the noto- 36 EMBRYOS OF ABOUT TWENTY HOURS’ INCUBATION 37 chordal plate or head process, which is temporarily united with the entoderm (Fig. 30). Neural Head groove process Mesoderm At A Primitive } knot ' Primitive groove C Primitive .C streak Area opaca : Blood island ; Fic. 30.—Dorsal surface view of a twenty-hour chick embryo showing primitive streak and extent of mesoderm (after Duval). X17. The lines A, B,and C indicate the levels of the corres- ponding sections shown in Fig. 31. Ectoderm Neural plate 4 A aie: 3 1 Pay BE. gee RRR. Set ease Mesoderm Notochordal plate Entoderm + ms ‘ Ectoderm Primitive knot Ule NStTNNS Nove) Be nis ee Mesoderm , Enloderm Ectoderm Primitive groove Mesoderm Entoderm Fic. 31.—Transverse sections through the embryonic area of a twenty-hour chick. X 165. A, through the head process; B, through the primitive knot; C, through the primitive streak. A transverse section through the primitive streak at twenty hours (see guide line C, Fig. 30) shows the three germ layers distinct laterally (Fig. 31C). In the 38 THE STUDY OF CHICK EMBRYOS midline, a depression in the ectoderm is the primitive groove. In this region there is no line of demarcation between ectoderm and mesoderm. A transverse section through the primitive knot (Fig. 31 B; guide line B, Fig. 30) shows the three germ layers intimately fused (cf. Fig. 51). There is a marked proliferation of cells, which are growing cephalad to form the notochordal plate (head process) (cf. Fig. 25). A transverse section through the notochordal plate, just beginning to form at this stage (Fig. 31 A; guide line A, Fig. 30), shows the thickening near the midline which will separate from the lateral mesoderm and form the notochord. It is fused with the entoderm but not with the ectoderm. After the notochordal plate becomes eae e tied BRA oc | ae Ie ree fos a é # : r prominent at twenty hours the differ- entiation of the germinal disc is rapid. A curved_fold, at involving the ectoderm and entoderm alone, is formed Sn ee ——___—_. cephalad of the notochordal_process. This is the head fold and is the anlage of the head of the embryo (Figs. 25 and 32). The ectoderm _has_thickened_on_ each sie OF she mud-dorsal Ie, fonning the 4 Primilive 4 segment b, Primitive neural folds. The groove between these The closure of this groove will form the neural tube, the an- is the neural groove. BAS PUP BT Ue = ai lage of the central nervous system. The Fic. 32.—Surface view of a twenty-one hour chick embryo, in which the head fold and first two pairs of primitive mesodermal seg- ments are present. The head process is seen under the neural groove (after Duval). x 13. notochord is now differentiated from the mesoderm and may be seen in the mid- dorsal line through the ectoderm. Inthe mesoderm lateral to the notochord and cephalad to the primitive node, transverse furrows have differentiated two pairs of block-like mesodermal segments, one incomplete cranially. As development proceeds these increase in number, successive pairs being developed caudally. They will be described in detail later. EMBRYO OF SEVEN SEGMENTS (TWENTY-FIVE HOURS’ INCUBATION) In this embryo (Fig. 33) there is a prominent network of blood vessels and blood cells in the saudal portion of the area opaca. In its cranial portion isolated groups of blood and blood vessel-forming cells are seen as blood islands. To- EMBRYO OF SEVEN SEGMENTS 39 gether, they constitute the angioblast from which arises the extra-embryonic blood vascular system. The area pellucida has the form of the sole of a shoe with broad toe directed forward. The head fold has become cylindrical and the head of the embryo is free for a short distance from the germinal disc. The mesoderm_ extends on each side beyond the head leaving a median. clear space, the proam- niotic area. The entoderm is carried forward in the head fold as the fore-gut, from Anterior neuro pore Pore-brain fj : Free portion of head Pharynx >. Fovea cardiaca ~ Right vilelline vein ——Neural groove a y 5 “Segmental sone Primitive knot Notochord Area opaca Blood island Primitive streak Fic. 33.—Dorsal view of a twenty-five-hour chick embryo with seven primitive segments. X 20. which later arise the pharynx, esophagus, stomach, and a portion of the small intestine. The opening into the fore-gut faces caudad and is the fovea cardiaca. The way in which the entoderm is folded up from the germinal disc and forward into the head is shown well in a longitudinal section of an older embryo (Fig. 42). The tubular heart lies ventral to the fore-gut and cranial to the fovea cardiaca. In later stages it is bent to the right. Converging forward to the heart, on each side of the jones are the vitelline veins, just making their appearance at this stage. 40 THE STUDY OF CHICK EMBRYOS The lips of the neural folds have met throughout the cranial two- thirds of the embryo but have not fused. The neura al tube, formed thus by. 7 the closing of the ectodermal folds, is open at either end at the neuropores. Cephalad, the neural tube has begun to expand to form the brain vesicles. Of these only the fore-brain is prominent, and from it the oplic vesicles are budding out laterally. The paraxial mesoderm is divided | by transverse furrows into seven pairs of block- like primitive “segments. Caudally, between the segments and the primitive streak, there is there is undifferentiated mesoderm, but new pairs of segments will develop in this region. Looking through the open neural tube (rhomboidal sinus), one may see in the midline the notochord extending from the primitive node cephalad until it is lost beneath the neural tube in the region of the primitive segments. The primitive streak is still prominent at the posterior end of the area pellucida, forming about one-fourth the length of the embryo. Transverse sections through the primitive streak and open neural groove show approximately the same conditions as in the twenty-hour embryo (Figs. 30 and 31). A Transverse Section through the Fifth Primitive Segment (Fig. 34) is characterized by the differentiation of the mesoderm, the approximation of the neural folds and the presence of two vessels, the descending aorta, on each side between the mesodermal segments and the entoderm. The neural folds are thick and the ectoderm is thickened over the embryo. The Neural groove Mesodermal segment Splanchnic mesoderm AD Recuesguees Cn sea Descending aorta Entoderm Fic. 34.—Transverse section through the fifth pair of mesodermal segments of a twenty-five-hour chick embryo. X 90. notochord is a sharply defined oval mass of cells. The mesodermal segments are somewhat triangular in outline and connected by the intermediate cell mass, or nephrotome, with the lateral mesoderm. This is partially divided by irregular flattened spaces into two layers, the dorsal of which is the somatic, the ventral the splanchnic layer of mesoderm. Later, the spaces unite on either side to form the celom or primitive body cavity. Transverse Section Caudal to the Fovea Cardiaca (Fig. 35).—The section is charac- terized: (1) by the closing together of the neural folds to form the newral tube; (2) by the dorsal and lateral folding of the entoderm, which, a few sections nearer the head end, forms the fore-gut or pharynx; (3) by the presence of the vitelline veins laterally between the ento- derm and mesothelium, (4) by the wide separation of the somatic and splanchnic mesoderm and the consequent increase in the size of the coelom. In this region the ccelom later sur- rounds the heart and forms the pleuro-pericardial cavity. EMBRYO OF SEVEN SEGMENTS 4I The neural tube at this level forms the third brain vesicle or hind-brain. The neural folds have not yet fused and at their dorsal angles are the neural crests, the anlages of the spinal ganglia. Mesodermal segments do not develop in this region; instead a diffuse net- work of mesoderm partly fills the space between ectoderm, entoderm, and mesothelium. This is termed mesenchyme and will be described later. Transverse Section through the Fovea Cardiaca (Fig. 36).—This section passes through a vertical fold of entoderm at the point where the latter is reflexed into the head as the Neural crest Ectoderm Descending aorta Se ? a ee —___Entoderm of fore-gut "ihe i Vitelline vein a ae He 3 Entoderm a ts ”, ¢ Fic. 35.—Transverse section caudal to the fovea cardiaca of a twenty-five-hour chick embryo. X 90. fore-gut (cf. Fig. 42). The entoderm forms a continuous mass of tissue between the vitelline veins thereby closing the fore-gut ventrally. The splanchnic mesoderm is differentiated into a thick-walled pouch on each side, lateral to the endothelial layer of the veins. Transverse Section through the Heart (Fig. 37).—Passing cephalad in the series of sections the vitelline veins open into the heart just in front of the fovea cardiaca. The entoderm in the head fold now forms the crescentic pharynx or fore-gut, separated by the heart and splanchnic mesothelium from the entoderm of the germinal disc. The descending Neural tube Descending aorta Notochord Fore-gut Splanchnic mesoderm (myocardium) : Endothelium of heart tube Celom— "ieecesete Entoderm ne Splanchnic mesoderm j# Fic. 36.—Transverse section through the fovea cardiaca of a twenty-five-hour chick embryo. X 90. aorte are larger, forming conspicuous spaces between the neural tube (hind-brain) and the pharynx. The heart, as will be seen, is formed by the union of two endothelial tubes, similar to those constituting the vitelline veins in the preceding sections. The median walls of these tubes disappear at a slightly later stage to form a single tube, the endocardium. Thickened layers of splanchnic mesoderm, which, in the preceding section, invested the vitelline veins laterally, now form the mesothelial wall of the heart. In the median ventral line, the layers of splanchnic mesoderm of each side have fused and separated from the splanchnic mesothe- 42 THE STUDY OF CHICK EMBRYOS lium of the germinal disc; thus the two pleuro-pericardial cavities are put in communication. The mesothelial wall of the heart forms the myocardium and epicardium of the adult. Dor- sally, the splanchnic mesoderm, as the dorsal mesocardium, suspends the heart, while still more dorsally it is continuous with the somatic mesoderm. Origin of Primitive Heart.—From the two sections last described, it is seen that the heart arises as a pair of endothelial tubes lying in the pockets of the splanchnic mesoderm. Later, the endothelial tubes fuse to form a single tube. The heart then consists of an endo- thelial tube within a thick-walled tube of mesoderm. The origin of the endothelial cells of the heart—whether they arise from entoderm or mesoderm—is not surely known. The vas- cular system is primitively a paired system, the heart arising as a double tube with two veins entering and two arteries leaving it. Origin of the Blood Vessels and Blood.—We have seen that in the area opaca a network of blood vessels and blood islands is differentiated as the_angioblast. This tissue gives rise to primitive blood vessels and blood cells and probably is derived from the splanch- nic mesoderm. The vessels arise first as reticular masses of cells, the so-called blood islands. These cellular thickenings undergo differentiation into two cell types, the innermost hecom- ing blood cells, the outermost forming a flattened endothelial layer which encloses the blood Ecloderm Neural tube Somatic mesoderm seer Notochord Descending aorta Pharynx Myocardium ; Endocardium Fic. 37.—Transverse section through the heart of a twenty-five-hour chick embryo. X 90 cells. All the primitive blood vessels of the embryo are composed of an endothelial layer only. The endothelial cells continue to divide, forming vascular sprouts and in this way new vessels are in part produced. The first vessels arising in the vascular area of a chick embryo unite into a close network, some of the branches of which enlarge to form vascular trunks. One pair of such trunks, the vile/line veins, is differentiated adjacent to the posterior end of the heart and later connects with it. Another pair, the vifelline artcrics, are developed in continuation with the aorte of the embryo. The vessels of the vascular area thus appear before those of the embryo have developed; they probably arise from the splanchnic meso- derm, and, both arteries and veins, are composed of a simple endothelial wall. As the coelom develops in the region of the vascular area of the embryo soon after the differentiation of the angioblast, the anlages of the blood vessels are formed only in the splanchnic layer. (For the development of the heart and blood vessels see Chapter IX.) Transverse Section through the Pharyngeal Membrane (Fig. 38).—This section passes through the head fold and shows the head free from the underlying germinal disc (cf. Fig. 42). The ectoderm surrounds the head and near the mid-ventral line it is bent dor- sad, is somewhat thickened, and comes in contact with the thick entoderm of the pharynx. The area of contact between ectoderm and pharvngeal entoderm forms the pharyngeal plate EMBRYO OF SEVENTEEN SEGMENTS 43 or membrane. Later, this membrane breaks through and thus the oral cavity arises. The expanded neural tube is closed in this region and forms the middle brain vesicle or mid-brain. The descending aortz appear as small vessels dorsal to the lateral folds of the pharynx. The blastoderm in the region beneath the head is composed of ectoderm and entoderm This is the proamntolic area. Laterad may be seen the layers of the mesoderm. Ectoderm aes oi fess ; Neural tube ORAL LEAS Ae EER Mesenchyma Gs hts ae i pM : AEE hopeet fab) he Su oe dh we Descending aorta x : SPA wtf ; ==— Fore-gut Pharyngeal € ; aN membrane con : SLE ; er gous egy. oars ero aaa Beers age lm tes a * Entoderm of Ke Tesoro w en nets Ectoderm of proamnion proamnion ae oo neetaeen noe NS Fic. 38.—Transverse section through the pharyngeal membrane of a twenty-five-hour chick embryo. x 90. Transverse Section through the Fore-brain and Optic Vesicle (Fig. 39).—The neural tube is open here and constitutes the first brain vesicle or fore-brain. The opening is the anterior neuropore. The ectoderm is composed of two or three layers of nuclei and is con- tinuous with the much thicker wall of the fore-brain. The lateral expansions of the fore- Neuropore Ectoderm Lctoderm— Optic vesicle 'plic vesicle —_. poeta | ean Proamnion — tig ee Fic. 39.—Transverse section through the fore-brain and optic vesicles of a twenty-five-hour chick. X 90. brain are the optic vesicles, which eventually give rise to the retina of the eye. The two ecto- dermal layers are in contact with each other except in the mid-ventral region, where the mesenchyma is beginning to penetrate between and separate them. The prearanide consists merely of a layer of ectoderm and of entoderm. CHICK EMBRYO OF SEVENTEEN PRIMITIVE SEGMENTS (THIRT Y-EIGHT HOURS) The long axis of this embryo is nearly straight (Fig. 40), the area pellucida is dumb-bell shaped and the vascular network is well differentiated throughout the area opaca. The tubular heart is bent to the embryo’s right, and opposite its _ posterior end the vascular network converges and becomes continuous with the trunks of the vitelline veins. Connections have also been formed between the descending aorte and the vascular area, but as yet the vitelline arteries have not 44 THE STUDY OF CHICK EMBRYOS appeared as distinct trunks. The proamniotic area is reduced to a small region in front of the head, which latter is now larger and more prominent. In the posterior third of the vascular area blood islands are still prominent. Central Nervous System and Sense Organs.—The neural tube is closed save at the caudal end where the open neural folds form the rhomboidal sinus. In PRT EY EA t UN ee GP LF Ie 7 4 Proamnion A ne) ~ Oplic vesicle Ve Fore-brain | Mid-brain« | Free porlion of head Hind-brain — re Heart it m { Vitelline vein ——~ =! 4 ee 2. Neural tube Mesodermal ‘” ay segment § t YT He a {; Notochord \_ : se AE SESE ee Le pe Pio ae oN. es Si I 2 HR ime Hill Fic. 40.—View of the dorsal surface of a thirty-eight-hour chick embryo. X 20. the head the neural tube is differentiated into the three brain vesicles, marked off from each other by constrictions. The fore-brain (prosencephalon) is charac- terized by the outgrowing optic vesicles. The mid-brain (mesencephalon) is merges caudally with the spinal cord. It shows a number of secondary constric- tions, the neuromeres. The ectoderm is thickened laterally over the optic ves- EMBRYO OF SEVENTEEN SEGMENTS 45 icles to form the lens placode of eye (Fig. 43). The optic vesicle is flattened at this point and will soon invaginate to produce the inner, nervous_layer_of the_ invaginated as the auditory placode (Fig. 45). This placode later forms the Pg »y Fore-brain Optic vesicle fe \\ Paired ventral aorta | \ 4 / Vy Phervnse! pouch 1 WG fr ot é yf + Descending ao Ventral aorta +42 le scending aorta Bulbus cordis Ventricle Splanchnic mesoderm —r 5 Left vitelline vein Fovea cardiaca — Entoderm § Right descendi ta eS aaa Section medullary tube Vascular plexus — Splanchnic mesoderm a ~—— Somatopleure Notochord A Descending aorta ff | Hl 4 | Mesbdermal t =I} | esodermal segmeni 4 | A | CD stetullary be | asm j yoo (|| id | ji S@\ 4 i | \ ‘ t \ \ —— Splanch ds Satyd j j Splanchnic mesoderm Beer ae , ated est 2-4 _____— Capillary plexus | 382 y oe Segmental zone Somatopleure _ ———— Neural groove Fic. 41.—Ventral reconstruction of a thirty-eight-hour chick embryo. The entoderm has been removed save about and caudal to the fovea cardiaca. X 38. otocyst or otic vesicle from which is differentiated the epithelium of the internal Digestive Tube.—The entoderm is still flattened out over the surface of the yolk caudal to the fovea cardiaca. In Fig. 41 the greater part of the entoderm iscutaway. The flattened fore-gut, folded inward at the fovea, shows indications 46 THE STUDY OF CHICK EMBRYOS of three lateral diverticula, the pharyngeal pouches. Cephalad the pharynx is closed ventrally by the pharyngeal membrane. Heart and Blood Vessels.—After receiving the vitelline veins cephalad to the fovea cardiaca the double-walled tube of the heart dilates and bends ventrad and to the embryo’s right (Fig. 41). It then is flexed dorsad and to the median line, and narrows to form the ventral aorta. The aorta lies ventrad to the pharynx and divides at the boundary line between the mid- and hind-brain into two ventral aorte. These diverge and course dorsad around the pharynx. Before reaching the optic vesicles they bend sharply dorsad and caudad, and, as the paired descending aortw, may be traced to a point opposite the last primitive seg- ments. In the region of the fovea cardiaca they lie close together and have fused to form a single vessel, the dorsal aorta. They soon separate and opposite the last primitive segments they are connected by numerous capillaries with the Hind-brain Fore-gut Neural tube Mid-brain Fore-brain = Amnion fold 4 Breasts Pharyngeal membrane Ventral aorta Dorsal Heart Pericardial cavity mesocardium Fic. 42.—A median longitudinal section of the head of a thirty-eight-hour chick embryo. X about 50. vascular network. In this region at a later stage the trunks of the paired vitelline arteries will be differentiated. The heart beats at this stage; the blood flows from the vascular area by way of the vitelline veins to the heart, thence by the aorte and vitelline arteries back again. This constitutes the vilelline circulation and through it the embryo receives nutriment from the yolk for its future develop- ment. In studying transverse sections of the embryo it is not sufficient merely to: identify the structures seen. The student should determine also the exact level of each section with respect to Figs. 40, 41 and 42, and trace the organs from sec- tion to section in the series. It is important to remember that the transverse sections figured and described in this manual (except those of the fifty-hour chick) are all drawn viewed from the cephalic surface; hence the right side of the embryo is at the reader’s left. EMBRYO OF SEVENTEEN SEGMENTS 47 TRANSVERSE SECTIONS Transverse Section through the Fore-brain and Optic Vesicles (Fig. 43).—The optic stalks connect the optic vesicles laterally with the ventral portion of the fore-brain. Dorsally the section passes through the mid-brain due to the somewhat ventrally flexed head Mid-brain Celom Somatopleure Fic. 43.—Transverse section through the fore-brain of a thirty-eight-hour chick embryo. X 75. (cf. Fig. 42). We have alluded to the thickening of the Jens placode. Note that there is now a considerable amount of mesenchyme between the ectoderm and the neural tube. Layers of mesoderm are present in the underlying blastoderm. Ectoderm Mid-brain Mesenchyme Descending aorta—f Fore-gut Veniral aorta Pharyngeal membrane Fic. 44.—Transverse section through the pharyngeal membrane of a thirty-eight-hour chick embryo. x 75. Transverse Section through the Pharyngeal Membrane and Mid-brain (Fig. 44).—In the mid-ventral line the thickened ectoderm bends up into contact with the entoderm of the rounded pharynx of the fore-gut. At this point the oral opening will break through. 48 THE STUDY OF CHICK EMBRYOS On either side of the pharynx a pair of large vessels are seen; the ventral pair are the ventral aorte. Two sections cephalad their cavities open into those of the dorsal pair, the descending aorte. The section is thus just caudad of the point where the ventral aorta bend dorsad and caudad to form the descending aorte. The section passes through the caudal end of the Ectoderm Hind-brain Ant. cardinal vein Notochord Auditory placode Descending aorta Pericardial cavity Somatic mesoderm : Bay Ectoderm Endothelium of ventricle Endothelium of bulbus Myocardium Fic. 45.—Transverse section through the hind-brain and auditory placodes of a thirty-eight-hour chick embryo. X 75. mesencephalon which is*here thick walled with an oval cavity. Note the large amount of undifferentiated mesenchyme in the section. The structure of the blastoderm is complicated by the presence of collapsed blood vessels. Transverse Section through the Hind-brain and Auditory Placodes (Fig. 45).— Besides the auditory placodes already described as the anlages of the internal ear, this sec- Ectoderm Hind-brain Mesodermal segment Fore-gut Anterior cardinat vein Descending aorta Somatic mesoderm Calom : Ectoderm Entoderm Splanchnic mesoderm Vitelline vein Heart Myocardium Fic. 46.—Transverse section through the caudal end of the heart of a thirty-eight-hour chick embryo. x 75. tion is characterized by (1) the large hind-brain, somewhat flattened dorsad; (2) the broad dorso-ventrally flattened pharynx, above which on each side lie the descending aorte; (3) the presence of the bulbar and ventricular portions of the heart. The bulbus is suspended dorsally EMBRYO OF SEVENTEEN SEGMENTS 49 by. the mesoderm, which here forms the dorsal mesocardium. The ventricle lies on the right side of the embryo; a few sections caudad in the series it is continuous with the ventral aorta (cf. Fig. 41). Between the somatic and splanchnic mesoderm is the large pericardial cavity. It surrounds the heart in this section. Dorsal to the aorta are the anterior cardinal veins, which return blood from the head region. Transverse Section through the Caudal End of the Heart (Fig. 46).—The section passes through the hind-brain. The descending aorte are separated only by a thin septum which is ruptured in this section. The anterior cardinal veins are cut at the level where they bend ventrad to enter the heart. The mesothelial wall of the heart is continuous with the splanchnic mesoderm. On the right side of the section there is apparent fusion between the myocardium of the heart and the somatic mesoderm. A pair of primitive meso- dermal segments may be seen in this section lateral to the hind-brain. It may be noted here that the primitive segments were not present in the sections of the head previously studied. Transverse Section through the Fovea Cardiaca (Fig. 47).—The descending aorie now form a single vessel, the dorsal aorta, the medium septum having disappeared. The Ectoderm Neural tube Mesodermal segment Notochord Dorsal aorta Calom Ant. card- inal vein Extra-embryonic celom NEenioderm Left vitelline vein Right vitelline vein Splanchnic mesoderm Entoderm Fore-gut Fic. 47.—Transverse section through the fovea cardiaca of a thirty-eight-hour chick embryo. X 90. section passes through the entoderm at the point where it is folded dorsad and cephalad into the head as the fore-gut (cf. Fig. 42). Two sections caudad is found the opening (fovea car- diacay where the fore-gut communicates with the flattened open gut between the entoderm and the yolk. On each side of the fore-gut are the large vitelline veins, sectioned obliquely. As the splanchnic mesoderm overlies these veins dorsad, it is pressed by them on each side against the somatic mesoderm and the cavity of the ccelom is thus interrupted. Transverse Section Caudal to the Fovea Cardiaca (Fig. 48).—This section re- sembles the preceding save that the primitive gut is without a ventral wall. The right vitelline vein is still large. Section through the Fourteenth Pair of Primitive Segments (Fig. 49)—The body of the embryo is now flattened on the surface of the yolk. Here the descending aorte are still separate and occupy the depressions lateral to the primitive segments. The section is characterized by the notochord and the differentiated mesoderm which forms the primitive segments, nephrotomes, somatic and splanchnic mesoderm, structures soon to be described. Arising from the nephrotomes are sprout-like pronephric tubules. The tips of these hollow out and unite to form the primary excretory or mesonephric duct. : 4 5° THE STUDY OF CHICK EMBRYOS Transverse Section through the Rhomboidal Sinus (Fig. 50).—The ‘neural groove is open, the notochord is ovalin form. The ectoderm is characterized by the columnar form of its cells. At the point where the ectoderm joins the neural fold a ridge of cells projects ven- Neural tube Neural cavity Mesodermal segment Celom Splanchnic mesoderm Splonchnablene Open gut Entoderm Fic. 48.—Transverse section caudal to the fovea cardiaca of a thirty-eight-hour chick embryo. X 90. Neural tube Mesodermal segment Ectoderm Central cells of segment. Somatic. mesoderm Pronephric tubule Sblanchnic mesoderm Descending aorta Entoderm Notochord Fic. 49.—Transverse section through the fourteenth pair of mesodermal segments of a thirty-eight-hour chick embryo. X 90. Neural groove Ectoderm Neural crest Segmental sone Somatic mesoderm ON AVS wee Splanchnic mesoderm Calom Notochord — Entoderm Blood vessel Fic. 50.—Transverse section through the rhomboidal sinus of a thirty-eight-hour chick embryo. X 90 trally on either side. These projecting cells form the nenral crests, and from them the spinal ganglia are formed. The mesodermal plates have split laterally into layers, but the coelomic cavities are mere slits. Between the splanchnic mesoderm and the entoderm blood vessels may be seen. EMBRYO OF SEVENTEEN SEGMENTS 51 Transverse Section through the Primitive (Hensen’s) Knot or Node (Fig. 51). —The section shows the three germ layers fused inseparably at the “knot” into a mass of Somatic mesoderm Ectoderm Primitive knot Celom Entoderm Splanchnic mesoderm Fic. 51.—Transverse section through the primitive (Hensen’s) knot of a thirty-eight-hour chick embryo. x 90. undifferentiated tissue. The mesoderm is split laterally into the somatic and splanchnic layers. Transverse Section through the Primitive Streak (Fig. 52).—In the mid-dorsal line is the primitive groove. The germ layers may be seen taking their origin from the undif- Somatic mesoderm Primitive groove Ectoderm DEUTER CAB Splanchnic mesoderm Entoderm Fic. 52.—Transverse section through the primitive streak of a thirty-eight-hour chick embryo. X 90. ferentiated tissue of the primitive streak beneath the primitive groove. Between the splanchnic mesoderm and entoderm blood vessels are present laterad as in the preceding sections. Mesodermal Segments.—We have seen that these are developed by the ap- pearance of transverse furrows in the mesoderm (Fig. 53). Later a longitudinal furrow partially separates the paired segments from the lateral unsegmented mesoderm. The segments are block-like with rounded angles when viewed dorsally, triangular in transverse sections (Figs. 49 and 53). They are formed cranio-caudally, the most cephalad being the first to appear. The first four lie in the head region. The segments contain no definite cavity but a potential cavity representing a portion of the ccelom is filled with cells, and the other cells of the segments form a thick mesothelial layer about them (Fig. 49). The ventral wall and a portion of the median wall of each primitive segment become trans- formed into mesenchyma which surrounds the neural tube and notochord (Fig. 290). The remaining portion of the segments persist as the dermo-muscular plates. The cells of the mesial portions of the plates, the myotomes, elongate and give rise 52 THE STUDY OF CHICK EMBRYOS to the voluntary muscle of the body. The voluntary or skeletal muscles are thus at first all segmented but later many of the segments fuse. In the trunk muscles of the adult fish the primitive segmented condition is retained. The Intermediate Cell Masses or Nephrotomes.—The bridge of cells con- necting the primitive segments with the lateral mesodermal layers constitutes the nephrotome (Figs. 49 and 53). In the chick the nephrotomes of the fifth to sixteenth segments give rise dorsad to pairs of small cellular sprouts, the rudi- mentary kidney tubules of the pronephroi, segmentally arranged in the fur- row lateral to the primitive segments. By the union of these cell masses dis- tally solid cords are formed which run lengthwise in the furrow. These cords fs a Mesonephric duct ——@ Neural tube Mesodermal segment Somatic mesoderm Splanchno pleure Descending aorla Notochord Entoderm Ci st Fic. 53.—Semi-diagrammatic reconstruction of five mesodermal segments of a forty-eight-hour chick embryo. The ectoderm is removed from the dorsal surface of the embryo. hollow out, grow caudad, and become the primary excretory (mesonephric) ducts (Fig. 53). More caudally the intermediate cell masses form the embryonic _kid- ney or mesonephros, the tubules of which open into the primary excretory duct. Further details concerning these provisional kidneys are given on pages 195-199, Since the genital glands develop in connection with the mesonephros, and the kidney of the adult (metanephros) is partly developed as an outgrowth of the primary y excretory duct, the intermediate cell mass may be regarded as the anlage of the urogenital glands and their ducis. These structures are thus of mesodermal origin. a es Somatopleure and Splanchnopleure.—In the embryo of seven primitive seg- ments the mesoderm was seen to split laterally into two layers, the somatic EMBRYO OF SEVENTEEN SEGMENTS 53 (dorsal) and the splanchnic (ventral) mesoderm (Fig. 34). These layers per= sist in the adult, the somatic mesoderm giving rise to the > pericardium of the heart, to the par. rietal plet pleura of the thorax and to the peritoneum | of the while the splanchnic layer forms the epicardium and myocardium of t the visceral pleura of the Jungs, and the mesenteries and mesodermal layer of the gut. The somatic mesoderm and the ectoderm, with the tissue developed be- tween them, constitute the body wall, which is termed the somatopleure. In the same way the splanchnic mesoderm and the entoderm, with the mesenchymal tissue between them, constitute the wall of the gut, or the splanchnopleure. Coelom.—The cavity between the somatopleure and splanchnopleure is the celom (body cavity). With the splitting of the mesoderm, isolated cavities are produced. These unite on Notochord Neural tube each side and eventually - Nephrotome form one cavity—the cce- lom. With the extension Archenteron of the mesoderm, the coe- SPlanchnic mesoderm Somatic mesoderm Sb leack aafle are. Yolk lom surrounds the heart and gut ventrally (Fig.54). --Euloderm Later, it is subdivided into Sia atofl uve the pericardial cavity about the heart, the pleural cavity of the thorax, and the peritoneal cavity of the ab- Celom dominal region. In the Fic. 54.—Diagrammatic transverse section of a vertebrate stages already studied, the embryo (adapted from Minot). embryo was flattened on the surface of the yolk and the somatopleure and splanchnopleure did not meet ventrally. If this union occurred they would conform to the structural relations shown in Fig. 54, which is essentially the ground plan of the vertebrate body. Mesenchyme.—In the sections through the head of this embryo, and through that of the preceding stage, but four primitive segments were found. The greater part of the mesoderm in the head appears in the form of an undifferentiated net- work of cells which fill in the spaces between the definite layers (epithelia). This tissue is mesenchyme (Fig. 55). The mesoderm may be largely converted into mesenchyme, as in the head, or any of the mesodermal layers may contribute to its formation. Thus it may be derived from the primitive segments and 54 THE STUDY OF CHICK EMBRYOS from the somatic and splanchnic mesoderm. The cells of the mesenchyme form a syncytium or network, and are at first packed closely together. Later, they may form a more open network with cytoplasmic processes extending from cell to cell (Fig. 55). The mesenchyme is an inportant Asshe Of Le em iye tissue of the embryo, from it. are differentiated the blood and 1 together ms. tomether with niost most of the smooth muscle, connective tissue, and skele- tal tissue of the body. The body of the embryo is now com- posed (1) of cells arranged in layers—epi- The term “epithelium” may be used in a general thelia, and (2) of diffuse mesenchyme. sense, or restricted to layers covering the surface of the body or lining the digestive canal and its derivatives. Layers lining the body cavities are termed mesothelia, while those lining the blood vessels and heart are Fic. 55.—Mesenchyme from the head of a thirty-eight-hour chick embryo. x 495. called endothelia. Derivatives of the Germ Layers.—The tissues of the adult are derived from the epithelia and mesenchyme of the three germ layers as follows: Ectoderm 1. Epidermis and its derivatives special sense. Mesoderm A. Mesothelium. . Serous layer of intestine. Entoderm 1. Epithelium of digestive 4, Epithelium of pharynx. (hair, nails, glands). 1. Pericardium. tract. 2. Conjunctiva and lens of eye. 2. Pleura. 2. Liver. 3. Sensory epithelia of organs of 3. Peritoneum. 3. Pancreas. 4 5 4. Epithelium of mouth, enamel . Epithelium .of most of urogeni- Eustachian tube. of teeth, oral glands. Hypo- tal organs. Tonsils. physis. 6. Striated muscle. Thymus. 5. Epithelium of anus. 1. Skeletal. Thyreoids. 6. Male urethra (distad). 2. Cardiac. Parathyreoids. 7. Epithelium of amnion and B. Mesenchyme. 5. Epithelium of respiratory chorion. 1. Blood cells. tract. 8. Nervous, neuroglia, and chro- 2. Bone marrow. Larynx. maffin cells of nervous sys- 3. Endothelium of blood vessels. Trachea. tem. Retina and optic nerve. 4. Endothelium of lymphatics. Lungs. 9. Notochord (?). 5. Spleen and lymphoid organs. 6. Epithelium of most of blad- 10. Smooth muscle of sweat glands 6. Supporting tissues. (Connect- der, of female urethra, and of iris. ing tissue, cartilage, and bone.) . Smooth muscle. male prostatic urethra and prostate. 7. Notochord (?). For the histological development (histogenesis) of the various tissues from the primary germ layers see Chapter X. EMBRYO OF TWENTY-SEVEN SEGMENTS 55 x CHICK EMBRYO OF TWENTY-SEVEN SEGMENTS (FIFTY HOURS) This embryo, of nearly fifty hours’ incubation, lies in the center of the vascular area and is peculiar in that the head is twisted 90° to the right. In a dorsal view, therefore, one sees the right side of the head but the dorsal side of the body. In the region of the mid-brain is a very marked bend, the cephalic flexure. Below the head, and ventral in position, lies the tubular heart, now bent in the form of Mid-brain Hind-brain § ; ; ‘ = Fore-brain Oplic vesicle | Lens vesicle Otic vesicle ire Branchial cleft 3 Bz Amnion fold L. vitelline artery + t R. vitelline artery Neural tube ; Segment 24 Area pellucida Primitive streak * and tail bud } Fic. 56.—Dorsal view of a fifty-hour chick embryo, stained and mounted in balsam. X 14. a letter S. Dorsal to the heart, in the region of the pharynx, three transverse grooves or slits may be seen. These are the branchial clefts or gill slits. The head of the embryo is now covered by a double fold of the somatopleure, the head fold of the amnion. It envelops the head like a veil. Caudally, a fold and opacity mark the position of the tail bud from which develops the caudal end of the body. The curved fold embracing this is the ¢azl fold of the amnion, which will eventually meet the head fold and completely envelop the embryo. Central Nervous System and Sense Organs (Fig. 57).—Cephalad, the neural 56 THE STUDY OF CHICK EMBRYOS tube is divided by constrictions into four vesicles. The fore-brain of the previous stage is now subdivided into two regions, the telencephalon and Hiencephalon. The cephalic flexure has been established in the region of the mesencephalon. The hind-brain, as yet undivided, equals the combined length of the other three vesicles. The lens of the eye has invaginated, pushing in the wall of the optic Mid-brain Optic vesicle FO xe Aperture of lens vesicle, . Hind-brain Ky YN, ‘\, Notochord ’ f SN \ Otocyst Pharynx i ey Ss {| Bulb of heart Fore-brain-+ Aortic arches 1, 2, 3 ey i | Ant. cardinal vein Ventricle Atrium R. vitelline vein Common cardinal vein . vitelline Post cardinal vein Fore-gut Descending aorta Splanchnopleure Liver anlage io Wi Fovea cardiaca Splanchnic mesoderm Entoderm Dorsal aorta Somatopleure R. vitelline sna, Mes. segment - . vilelline artery Edge of splanchnic mesoderm Mes. segment Vascular plexus Segmental zone Neural plate Entoderm 7 Primitive node “& ee Fic. 57.—Semi-diagrammatic reconstruction of a fifty-hour chick embryo, in ventral view. X 18. The entoderm has been removed save in the region of the fovea cardiaca and of the hind-gut. Owing to the torsion of the embryo, the cranial third of the embryo is seen from the left side, the caudal two- thirds in ventral view. vesicle and thus forming a double-walled structure, the optic cup. The audi- tory placode has become a sac, the ofocyst, which overlies the hind-brain opposite the second branchial groove and is still connected with the outer ectoderm, cut away in Fig. 57. The rhomboidal sinus is still open at the caudal end of the neural tube. EMBRYO OF TWENTY-SEVEN SEGMENTS 57 Digestive Canal (Fig. 57).—In a reconstruction from the ventral side, the digestive canal shows differentiation into three regions. Of these, the fore-gut has been seen in earlier stages. A greater part of the mid-gut has been cut away to show the underlying structures; it is without a ventral wall and overlies the yolk. Caudad, a small fovea leads into the hind-gut which is just beginning to evag- inate into the tail fold. The pharyngeal membrane now lies in a considerable cavity, the stomedgum, formed by the invaginated ectoderm. The median ecto- dermal pouch next the brain wall is known as Rathke’s pocket and is the anlage of the anterior lobe of the hypophysis. The pharynx shows laterally three out- pocketings, of which the first is wing-like and is the largest. These pharyngeal pouches occur opposite the three branchial grooves and here entoderm and ecto- derm are in contact, forming the closing plates. At about this stage the first closing plate ruptures, thereby forming a free opening, or branchial cleft, into the pharynx. Between the pouches are developed the branchial arches, in which course the paired aortic arches. Towards the fovea cardiaca the fore-gut is flat- tened laterally and before it opens out into the mid-gut there is budded off ven- teally a bilobed structure, the anlage of the liver (Figs. 57 and 63). It lies be- tween the vitelline veins and in its later development the veins are broken up into the sinusoids or blood spaces of the liver. Just as the entoderm participates in the head fold to form the fore-gut so in the tail fold it forms the hind-gut. This at once gives rise to a tubular outgrowth which becomes the allantois, one of the fetal membranes to be described later (Fig. 70). Blood Vascular System.—The tubular heart is flexed in the form of a letter S when seen from the ventral side. Four regions may be distinguished: (1) the sinus venosus, into which open the veins; (2) a dilated dorsal chamber, the atrium; (3) a tubular ventral portion flexed in the form of a U, of which the left limb is the ventricle, the right limb (4) the bulbus cordis. From the bulbus is given off the ventral aorta. There are now developed three pairs of aortic arches which open into the paired descending aorte. The first aortic arch passes cranial to the first pharyngeal pouch and is the primitive arch seen in the thirty- six-hour embryo. The second and third arches course on either side of the second pharyngeal pouch. They are developed by the enlargement of channels in primitive capillary networks between ventral and descending aorte. Op- posite the sinus venosus the paired aortic trunks fuse to form the single dorsal aorta which extends as far back as the fifteenth pair of primitive segments. At this point the aorte again separate, and, opposite the twentieth segments, each 58 THE STUDY OF CHICK EMBRYOS connects with the trunk of a vitelline artery which was developed in the vascular area and conveys the blood to it (Fig. 57). Caudal to the vitelline arteries the dorsal aorte rapidly decrease in size and soon end. As in the previous stage, the blood is conveyed from the vascular area to the heart by the vitelline veins, now two large trunks. In the body of the embryo there have developed two pairs of veins. In the head have appeared the anterior cardinal veins, already of large size and lying lateral to the ventral region of the Chorion Hind-brain Amnion Ant. cardinal vein Notochord \ Aorlic arch 1 Ectoderm Lens vesicle} A—O plic vesicle ic Prosencephalon Cavity of fore-brain Fic. 58.—Transverse section through the fore-brain and eyes of a fifty-hour chick embryo. X SO. brain vesicles (Fig. 60). Caudal to the atrium of the heart, two small posterior cardinal veins are developed. They lie in the mesenchyma of the somatopleure laterad in position (Fig. 63). Opposite the sinus venosus the anterior and pos- terior cardinal veins of each side unite and form the common cardinal veins (ducts of Cuvier) which open into the dorsal wall of the sinus venosus (Fig. 57). The primitive veins are thus paired like the arteries, and like them develop by the en- largement of channels in a network of capillaries. The following series of transverse sections from an embryo of this stage shows EMBRYO OF TWENTY-SEVEN SEGMENTS 59 the more important structures. The approximate plane and level of each section may be ascertained by referring to Figs. 56 and 57. TRANSVERSE SECTIONS Section through the Fore-brain and Eyes (Fig. 58).—The section passes cranial to the optic stalks, consequently the optic vesicles appear unconnected with the fore-brain. The thickened ectoderm is invaginated to form the anlages of the lens vesicles. The thicker wall of the optic vesicles next the lens anlage will give rise to the nervous layer of the retina, the thinner outer wall becomes the pigment layer of the retina. Ventrad in the section are the wall and cavity of the fore-brain, dorsad the hind-brain with its thin, dorsal ependymal layer. Amnion Hind-brain_ KAA i Chorion Ant. cardinal vein . aoe Descending aorta— Ecloderm ; : Pharynx Ant. cardinal vein ’ Rathke’s pocket Ventral aorta Optic vesicle. Fic. 59.—Transverse section through the optic stalks and hypophysis of a fifty-hour chick embryo. x 50. Between the brain vesicles on either side are sections of the first aortic arches and lateral to the hind-brain are the smaller paired anterior cardinal veins, which convey the blood from the head to the heart. Section through the Optic Stalks and Hypophysis (Fig. 59).—The section passes just caudal to the lens which does not show. The offic vesicles are connected with the wall of the fore-brain by the optic stalks which later form the path by which the fibers of the optic nerve pass from the retina to the brain. Both the ventral and the descending aorte are seen in section about the cephalad end of the pharynx. Between the ventral wall of the fore-brain and the pharynx is an invagination of the ectoderm, Rathke’s pocket (anterior lobe of hypophysis). Missing Page Missing Page 62 THE STUDY OF CHICK EMBRYOS The somatopleuric folds of the amnion envelop the right side of the embryo and the ectoderm of these folds now forms the outer layer of the chorion and the inner layer of the amnion. The mesodermal components of these folds have not united. Section through the Anlage of the Liver (Fig. 63).—In this section the cavity of the fore-gut is narrow, the gut being flattened from side to side. Ventrad there are evaginated from the entoderm two elongate diverticula which form the anlages of the /iver. On either side of the anlages of the liver are sections of the vifelline veins on their way to the sinus venosus at a higher level in the series. Note the intimate relation between the entodermal epithelium of the liver and the endothelium of the vitelline veins. In later stages, as the liver anlages branch, there is, as Minot aptly expresses it, “‘an intercrescence of the entodermal cells consti- tuting the liver and of the vascular endothelium” of the vitelline veins. Thus are formed the hepatic sinusoids of the portal system, which surround the cords of hepatic cells. Fic. 63.—Transverse section through the anlage of the liver of a fifty-hour chick embryo. xX 50. The septum transversum is still present at this level and lateral to the fore-gut are small body cavities. Lateral to the body cavities appear branches of the posterior cardinal veins. Section through the Cranial Portion of the Open Intestine (Fig. 64).—The intestine is now open ventrad, its splanchnopleure passing directly over to that of the vascular area. The folds of the amnion do not join, leaving the amniotic cavity open. The dorsal aorta is divided by a septum into its primitive components, the right and left descending aorte. Lateral to the aorte are the small posterior cardinal veins. The ccelom is in communication with the extra-embryonic body cavity. Section through the Seventeenth Pair of Mesodermal Segments (Fig. 65).—The body of the embryo is now no longer flexed to the right. On the left side of the figure the mesodermal segment shows a dorso-lateral muscle plate. The median and ventral portion of the segment is being converted into mesenchyme. On the right side appears a section of the primary excretory or mesonephric duct. The embryonic somatopleure is arched and will form EMBRYO’ OF TWENTY-SEVEN SEGMENTS 63 the future ventro-lateral body wall of the embryo. The fold lateral to the arch of the somato- pleure gives indication of the later approximation of the ventral body walls, by which the embryo is separated from the underlying layers of the blastoderm. Chorion \ Amnion Central canal ays Ni 2 Spinal cord Mesodermat segment R. descending aorta -—~ Somato pleure Fic. 64.—Transverse section through the cranial portion of the open intestine of a fifty-hour chick embryo. X 50. Section through the Origin of the Vitelline Arteries (Fig. 66).—At this level the embryo is more flattened and simpler in structure, the section resembling one through the mid-gut region of a thirty-eight-hour chick (Fig. 49). The amniotic folds have not appeared. Spinal cord Mesodermal segment Descending aorta Somato pleure Ectoderm Notochord Somatic mesoderm aS Splanchnic mesoderm Celom Entoderm Fic. 65.—Transverse section through the seventeenth pair of mesodermal segments of a fifty-hour chick embryo. X SO. On the left side of the figure the vitelline artery leaves the aorta. On the right side the con- nection of the vitelline artery with the aorta does not show, as the section is cut somewhat obliquely. The posterior cardinal vein is present just laterad of the right mesonephric duct. The other structures were described in connection with Fig. 49. 64 THE STUDY OF CHICK EMBRYOS Section Caudal to the Mesodermal Segments (Fig. 67).—The mesodermal seg- ments are replaced by the segmental zone, a somewhat triangular mass of undifferentiated mesoderm from which later are formed the segments and nephrotomes. The notochord is Mesodermal segment Spinal cord Nephrotome Ectoderm e Mesonéphric duct Calom Somatic mesoderm Somato pleure Entoderm Aorta and vitelline — Notochord artery Fic. 66.—Transverse section of a fifty-hour chick embryo at the level of the origin of the vitelline arteries. x 50. larger, the aorte smaller, and a few sections caudad they disappear. Laterally the somato- pleure and splanchnopleure are straight and separated by the slit-like ccelom. Section through the Primitive Knot Cranial to the Hind-gut (Fig. 68).—With the exception of the ectoderm, the structures near the median line are merged into an undiffer- Spinal cord Ectoderm Descending aorta Somatic mesoderm Segmental sone Somatic mesoderm Splanchnic mesoderm Notochord Entoderm Fic. 67.—Transverse section of a fifty-hour chick embryo through the segmental zone caudal to the meso- dermal segments. x 50. entiated mass of tissue. The cavity of the neural tube and its dorsal outline may still be seen, but its ventral portion, the notochord, mesoderm, and entoderm, blend in a dense mass of tissue which is characteristic of the primitive knot. Laterally the segmental zone and the various layers are differentiated. Neural tube Ectoaerm Segmental sone Splanchnopleure Entoderm Notochordal plate Fic. 68.—Transverse section of a fifty-hour chick embryo through the primitive node cranial to the hind-gut. X 50. Section Passing through the Hind-gut (Fig. 69).—In this embryo the caudal evagina- tion to form the Aind-gut has just begun. The section shows the small cavity of the hind+ EMBRYO OF TWENTY-SEVEN SEGMENTS 65 gut in the midline. Its wall is composed of columnar entodermal cells and it is an out- growth of the entodermal layer. Dorsal to the hind-gut may be seen undifferentiated cells Primitive knot Ectoderm Hind-gut Entoderm Fic. 69.—Transverse section passing through the hind-gut of a fifty-hour chick embryo. X 50. of the primitive streak continuous dorsad with the ectoderm, ventrad with the entoderm of the hind-gut, and laterally with the mesoderm. In the chick embryos which we have studied, there are large areas developed which are extra-embryonic, that is, lie outside the embryo. The splanchnopleure of the area vasculosa, for instance, forms the wall of the yolk sac, incomplete in the early stages. The amnion, chorion, and allantois are extra-embryonic mem- branes which make their appearance at the fifty-hour stage. These structures are important in mammalian and human embryos and a description of their further development in the chick, where their structure and mode of develop- ment is primitive, will lead up to the study of mammalian embryos in which the amnion and chorion are précociously developed. Amnion and Chorion.—These two membranes are developed in all amniote vertebrates (Reptiles, Birds, and Mammals). They are derived from the extra- embryonic somatopleure. The amnion is purely a protective structure, but the chorion of mammals has a trophic function, as through it the embryo derives its nourishment from the uterine wall. Fig. 70 A shows the amnion and chorion developing. The head fold of the somatopleure forms first and envelops the head, the tail fold makes its appearance later. The two folds extend laterad, meet and fuse (Fig. 70 B, C). The inner leaf of the folds forms the amnion, the re- mainder of the extra-embryonic somatopleure becomes the chorion. The actual appearance of these structures and their relation to the embryo have been seen in Figs. 63 and 64. The amnion, with its ectodermal layer inside, completely sur- rounds the embryo at'the end of the third day, enclosing a cavity filled with am- niotic fluid (Fig. 71). In this the embryo floats and is thus protected from injury. The chorion is of little importance to the chick. It is at first incomplete, but eventually entirely surrounds the embryo and its other appendages. Yolk Sac and Yolk Stalk.—While the amnion and chorion are developing during the second and third day, the embryo grows rapidly. The head- and tail 5 66 THE STUDY OF CHICK EMBRYOS folds elongate and the trunk expands laterally until only a relatively narrow stalk of the splanchnopleure connects the embryo with the | yolk. This portion of the splanchnopleure has grown more slowly than the body of the embryo and is termed the yolk stalk. It is continuous with the splanchnopleure which envelops the yolk and forms the yolk sac. The process of unequal growth by which the embryo becomes separated from the yolk has been described as a process of constriction. This, as Minot points out, is anerror. The splanchnopleure at first forms only an oval plate on the surface of the yolk, but eventually encloses it. In Fig. 70, C and D, the relation of the embryo to the yolk sac is seen at the end of the first week of incubation. The vitelline vessels ramify on the surface of the yolk sac and Fic. 70.—Diagrams showing the development of the amnion, chorion and allantois in longi- tudinal section (Gegenbaur in McMurrich). Ectoderm, mesoderm, and entoderm represented by heavy, light, and dotted lines respectively. Af. amnion folds; Al., allantois; Am., amniotic cavity; Ch., chorion; Vs., yolk sac. through them all the food material of the yolk is conveyed to the chick during the incubation period (about twenty-one days). Allantois.—-We have seen that in the fifty-hour chick a ventral evagination, the hind-gut, develops near its caudal end (Fig. 69). From it develops the anlage of the allantois, which, as an outgrowth of the splanchnopleure, is lined with entoderm and covered with splanchnic mesoderm (Fig. 70). It develops rapidly into a vesicle connected to the hind-gut by a narrow stalk, the allantoic stalk. At the fifth day the allantois is nearly as large as the embryo (Fig. 71). Its wall flattens out beneath the chorion and finally it lies close to the shell but is attached only tothe embryo. The functions of respiration and excretion are ascribed to it. EMBRYO OF TWENTY-SEVEN SEGMENTS 67 In its wall ramify the allantoic vessels, which have been compared to the umbilical arteries and veins of mammalian embryos. The chick embryo is thus protected by the amnion which develops from the inner leaf of the folded somatopleure and is composed of an inner ectodermal and an outer mesodermal layer. Nutriment for the growth of the embryo is supplied by the yolk sac and carried to the embryo by the vitelline veins. The allantois, Allantois Embryo Amnion Chorion Shell Y, Shell membrane Volk sac d, Margin of area vasculosa Air chamber Fic. 71.—Diagram of a chick embryo at the end of the fifth day showing amnion, chorion and allan- tois (Marshall). X 1.5. which takes its origin from the splanchnopleure of the hind-gut and is composed of an inner layer of entoderm and an outer layer of splanchnic mesoderm, func- tions as an organ of respiration and serves as a reservoir for the excreta of the embryonic kidneys. As we shall see, the allantois becomes more important, the yolk sac less important in some mammals, while in human embryos both yolk sac and allantois are unimportant when compared to the chorion. CHAPTER IV THE FETAL MEMBRANES AND EARLY HUMAN EMBRYOS THE fetal membranes of mammals include the amnion, chorion, yolk sac, and . allantois, structures which we have seen are present in chick embryos. Most important in mammals is the manner in which the embryo becomes attached to the uterine wall of the mother, and in this regard mammalian embryos fall into two groups. Among the Ungulates or hoofed mammals (e. g., the pig) the fetal membranes are of a primitive type, resembling those of the chick. Among Unguiculates (clawed animals like the bat and rabbit) and Primates (e. g., Man) the fetal membranes of the embryo show marked changes in development and structure. FETAL MEMBRANES OF THE PIG EMBRYO The amnion and chorion develop very much as in the chick embryo (Fig. 70 A, B). Folds of the somatopleure form very early and envelop the whole embryo. = Seon cord Ny olochord Mesodermal segment Amniotic cavily_ 4 Upper limb bud 4) i: Posterior cardinal vein Dorsal aorla—— ye ~~ Entoderm of gut Splanchnic mesoderm Fic. 72.—Transverse section through the yolk sac and stalk of a 5 mm. pig embryo showing attachment of amnion. The amnion (Fig. 72) is closed in embryos with but a few pairs of segments, but for some time remains attached to the chorion by a strand of tissue (Keibel). The yolk sac develops early as in all mammals. In the pig it is small and the greater part of it soon degenerates. It is important only in the early growth of the 68 FETAL MEMBRANES OF THE PIG EMBRYO 69 embryo, its functions then being transferred to the allantois. Branches of the vitelline vessels ramify in its wall, as in that of chick embryos, but soon degener- ate. The trunks of the vitelline vessels, however, persist within the body of the embryo. The allantois, developing as in the chick from the ventral wall of the hind-gut (Fig. 70 A-D), appears when the embryo is still flattened out on the germinal disc. In an embryo 3.5 mm. long it is crescent-shaped and as large as the embryo. It soon becomes larger and its convex outer surface (splanchnic mesoderm) is applied to the inner surface (somatic mesoderm) of the chorion. Entoderm of primitive gut Amnion Ectoderm oko Z 3s Somatic and ya splanchnic mesoderm ear 9 ‘0 ig os Hi 75 > pA aaa y a/\% O35 Yolk sac Tunica propria of uterus Fic. 73.—Diagram of the fetal membranes and allantoic placenta of a pig embryo in median sagittal sec- tion (based on figures of Heisler and Minot). These surface layers fuse more or less completely. A pair of allantoic veins and arteries branch in the splanchnic layer of the allantois. These branches are brought into contact with the mesodermal layer of the chorion and invade it. The outer ectodermal layer of the chorion in the meantime has closely applied itself to the uterine epithelium, the ends of the uterine cells fitting into depressions in the chorionic cells (Fig. 73). When the allantoic circulation is established, waste products given off from the blood of the embryo must pass through the epithelia of both chorion and uterus to be taken up by the blood of the mother. iy 7O THE FETAL MEMBRANES AND EARLY HUMAN EMBRYOS In the same way nutritive substances and oxygen must pass from the maternal blood through these layers to enter the allantoic vessels. This exchange does take place, however, and thus in Ungulates the allantois has become important not only as an organ of respiration and excretion but as an organ of nutrition. Through its vessels it has taken on a function belonging to the yolk sac in birds, and we now see why the! yolk sac becomes a rudimentary structure in the higher mam- mals. Excreta from the embryonic kidneys are passed into the cavity of the allantois which is relatively large. The name is derived from a Greek word mean- ing sausage-like, from its form in some animals. The chorion is important only as it brings the allantois into close relation to the uterine wall, but in man we shall see that it plays a more important rdle. UMBILICAL CORD Pig Embryos.—In their early development the relation of the amnion, allan- tois, and yolk sac to each other and to the embryo is much the same as in the chick of five days (Fig. 71). With the increase in size of the embryo, however, the somatopleure in the region of the attachment of the amnion grows ventrad (Fig. 70D). Asa result, it is carried downward about the yolk sac and allantois, forming the umbilical cord (cf. Fig. 241). Thus in a pig embryo 10 to 12 mm. long the amnion is attached at a circular line about these structures some distance from the body of the embryo (cf. Fig. 119). The ccelom at first extends ventrad into the cord, but later the mesodermal layers of amnion, yolk stalk, and allantois fuse and form a solid cord of tissue. This is the umbilical cord of fetal life and its point of attachment to the body is the wmbilicus or navel. The cord is covered by a layer of ectoderm continuous with that of the amnion and of the embryo and contains, embedded in a mesenchymal (mucous) tissue, (1) the yolk stalk and (in early stages) its vitelline vessels; (2) the allantoic stalk; (3) the allantoic vessels. These latter, two arteries and a single large vein, are termed, from their position, the umbilical vessels. At certain stages (Figs. 122 and 123) the gut normally extends into the coelom of the cord, forming an umbilical hernia. Later, it re- turns to the coelom of the embryo and the cavity of the cord disappears. The umbilical cord of the pig is very short. Human Umbilical Cord.—This develops like that of the pig and may attain a length of more than 50 cm. It becomes spirally twisted, just how is not known. In embryos from 10 to 40 mm. long the gut extends into the ccelom of the cord (Figs. 179 and 180). At the 42 mm. stage, according to Lewis and Mall, the gut returns to the coelom of the body. The mucous tissue peculiar to the cord EARLY HUMAN EMBRYOS AND THEIR MEMBRANES 71 arises from mesenchyme. It contains no capillaries and no nerves, but embed- ded in it are the large umbilical vein, the two arteries, the allantois, and the yolk stalk. The umbilical cord may become wound about the neck of the fetus, caus- ing its death and abortion, or by coiling about the extremities it may lead to their atrophy or amputation. EARLY HUMAN EMBRYOS AND THEIR MEMBRANES Referring to the blastodermic vesicle of the mammal (Figs. 17 and 18), it is found to consist of an outer layer, which we have called the trophectoderm, and the inner cell mass (p. 36). The trophectoderm forms the primitive ectodermal layer of the chorion in the higher mammals and probably in man. From the inner cell mass are derived the primary ectoderm, entoderm, and mesoderm. In the earliest known human embryos described by Teacher, Bryce, and Peters, the germ layers and amnion are present, indicating that they are formed very early. We can only infer their early origin from what is known of other mammals. The diagrams (Fig. 74 A and B) show two hypothetical stages seen in median longi- tudinal section. In the first stage (A) the blastodermic vesicle is surrounded by the trophectoderm layer. The inner cell mass is differentiated into a dorsal mass of ectoderm and a ventral mass of entoderm. Mesoderm more or less completely fills the space between entoderm and trophectoderm. It is assumed that as the embryo grows (B) a split occurs in the mass of ectoderm cells, giving rise to the amniotic cavity and dividing these cells into the ectodermal layer of the embryo and into the extra-embryonic ectoderm of the amnion. At the same time a cavity may be assumed to form in the entoderm, giving rise to the primitive gut. About this stage the embryo embeds itself in the uterine mucosa. In the third stage, based on Peter’s embryo (C), the extra-embryonic mesoderm has extended between the trophectoderm and the ectoderm of the amnion and the extra- embryonic ccelom appears. At first strands of mesoderm, known as the magma reticulare, bridge across the ccelom between the somatic and splanchnic layers of mesoderm (Fig. 76). The amniotic cavity has increased in size and the embryo is attached to the trophectoderm by the unsplit layer of mesoderm between the ectoderm of the amnion and the trophectoderm of the chorion. The latter shows thickenings which are the anlages of the chorionic villi surrounded by trophoderm cells. In the fourth stage, based on Graf Spee’s embryo (D), the chorionic villi are longer and branched. The mesoderm now remains unsplit only at the pos- terior end of the embryo, where it forms the body stalk peculiar to Unguiculates and Primates. It connects the mesoderm of the embryo with the mesoderm of the 72 THE FETAL MEMBRANES AND EARLY HUMAN EMBRYOS chorion. Into it there has grown from the gut of the embryo the entodermal diver- ticulum of the allantois. The Chorion.—The human chorion is derived directly from the outer troph- ectoderm layer of the blastodermic vesicle and from the extra-embryonic somatic mesoderm. Its early structure resembles that of the pig’s chorion. The troph- ectoderm of the human embryo early gives rise to a thickened outer layer, the trophoderm (syncytial and nutrient layer—Figs. 74 C and 239). When the develop- Trophectoderm Archenteron: Entoderm Mesoderm Ectoderm of amnion Ectoderm of embryo f yo | Ectoderm of embryo Cavity of amnion ALesoderm o, Tro phectoderm amn a Amniotic cavily Volk sae Ectoderm of _ Sy chorion = Entoderm Cavity of yolk : . : Sac=BF a 3 Splanchnic Entoderm of: mesoderm yolk sac Extra-embry- Mfesoderm onic celom of yolk sac Extra-embry- onic celom derm Mesoderm Trophoderm of chorion Chorionic villi Fic. 74.—Four diagrams of early human embryos (based on figures of Robinson and Minot). 4A, Hy- pothetical stage; B, Bryce-Teacher embryo (modified); C, Peter’s embryo; D, Graf Spee’s embryo. ing embryo comes into contact with the uterine wall the trophoderm destroys the maternal tissues. The destruction of the uterine mucosa serves two purposes: (1) the embedding and attachment of the embryo, it being grafted, so to speak, to the uterine wall; and (2) it supplies the embryo with a new source of nutrition. To obtain nutriment to better advantage, there grow out from the chorion into the uterine mucosa branched processes or villi. The villi are bathed in maternal blood, and in them blood vessels are developed, the trunks of which pass to and EARLY HUMAN EMBRYOS AND THEIR MEMBRANES 73 from the embryo as the umbilical vessels. ‘The embryo receives its nutriment and oxygen, and gets rid of waste products through the walls of the villi. The region where the attachment of the chorionic villi to the uterine wall persists during fetal life is known as the placenta. It will be described later with the decidual mem- branes of the uterus. We saw how the allantois of Ungulates had assumed the Inner cell mass Embryonic ectoderm Entoderm Maternal blood vessels Lo Trophoderm oT 6) BES 5 a Cytolrophoblast , G (Gr ares file Ly. geese! Of Oe re See Amniotic cavity gO, wih fli? ph as Embryonic ectoderm Entoderm Fic. 75.—Sections showing the formation of the amnion in bat embryos (after Van Beneden). X about 160. nutritive functions performed by the yolk sac in birds, with a consequent degene- ration of the ungulate yolk sac. In man and Unguiculates the functions of the allantois are transferred to the chorion, and the allantois, in turn, becomes a rudi- mentary structure. The Amnion.—This is formed precociously in Unguiculates and in a manner quite different from its mode of origin in Ungulates and birds. It is assumed that 74 THE FETAL MEMBRANES AND EARLY HUMAN EMBRYOS its cavity arises as a split in the primitive ectoderm of human embryos, as in bat embryos (Fig. 75). Later,a somatic layer of mesoderm envelops its ectodermal layer, its component parts then being the same as in birds and Ungulates—an inner layer of ectoderm and an outer layer of mesoderm (F ig. 74D). It becomes a thin, pellucid, non-vascular membrane and about a month before birth is in contact with the chorion. It then contains about a liter of amniotic fluid, the origin of which is unknown. During the early months of pregnancy the embryo, suspended by the umbilical cord, floats in the amniotic fluid. The embryo is protected from maceration by a whité fatty secretion, the vernix caseéosa. At birth the amnion is ruptured either normally or artificially. If not ruptured, the child may be born enveloped in the amnion, popularly known as a veil or ‘“‘caul.”” The hte v ae oe & e 3 9, amas a eee Va S =e. ee 3 | | rN So i = f z i a wa 028 © ATH Oh LS a= as ’ aoe ae ea" oo eh, mes. 70 © aes go aur? Gor ees MCS. ei ge ae 2 ae . > eo ° *: ah “i © ex. Ca. ent. Fic. 76.—Section of Peter’s embryo of 0.2 mm. (about fifteen days). ect., Ectoderm of chorion; mes., mesoderm; am., amniotic cavity; em. pl., embryonic plate; y.s., yolk sac; ent., entoderm; ex. c@., portion of extra-embryonic ccelom limited by a strand of the magma reticulare. amniotic fluid may be present in excessive amount, the condition being known as hydram- mios. If less than the normal amount of fluid is present, the amnion may adhere to the embryo and produce malformations. It has been found, too, that fibrous bands or cords of tissue may extend across the amniotic cavity, and, pressing upon parts of the embryo during its growth, may cause scars and splitting of eyelids or lips. Such amniotic threads may even amputate a limb or cause the bifurcation of a digit. The Allantois.—The allantois appears very early in the human embryo be- fore the development of the fore-gut or hind-gut. In Peter’s embryo the amnion, chorion, and yolk sac are present, but not the allantois (Fig. 76). In an embryo 1.54 mm. long, described by Von Spee (Fig. 77), there is no hind-gut, but the EARLY HUMAN EMBRYOS AND THEIR MEMBRANES 75 allantoic diverticulum of the entoderm has invaded the mesoderm of the body stalk. This embryo, seen from the dorsal side with the amnion cut away, shows Neurenteric canal = Primitive streak Body stalk _—_—_4.— Ba : Villi of chorion ae Embryonic disc LS Rudiment of heart Mesoderm Fic. 77.—Views of a human embryo 1.54 mm. long (Graf Spee). > 23. A, Dorsal surface; B, median sagittal section. a marked neural groove and primitive streak. In front of the primitive knot a pore is figured leading from the neural groove into the primitive intestinal 76 THE FETAL MEMBRANES AND EARLY HUMAN EMBRYOS cavity, and hence called the neurenteric canal (p. 33). The fore-gut and head fold have formed at this stage and there are branched chorionic villi. Somewhat more advanced conditions are found in > Amnion (cut) an embryo of 1.8 mm. with five to six pairs of segments (Fig. 78). A reconstruction by Dandy of Volk sac Mall’s embryo, about 2 mm. long with Neurenteric canal S&VeN pairs of segments, shows well 5 Primitive streak the embryonic appendages (Fig. 79). —— Body stalk ~~~ Chorion The fore- and hind-gut are well de- om s veloped, the amniotic cavity is large, Fic. 78 —Kroémer human embryo of 1.8 mm. in and the yolk sac still communicates dorsal view (after Keibel and Elze). > 20. with the gut through a wide opening. The allantois is present as a long curved tube somewhat dilated near its blind end and embedded in the mesoderm of the body stalk. As the hind-gut Chorion Amnion . on ~ , Body stalk Pharyngeal oO ee W Allantoic membrane f Fore-gut Heart’ #f Splanchnic mesoderm Fic. 79.—A human embryo of 2 mm. in median sagittal section (adapted from reconstructions of Mall’s embryo by F. T. Lewis and Dandy). X 23. develops, the allantois comes to open into its ventral wall. A large umbilical artery and vein are present in the body stalk. In an embryo of 23 somites 2.5 mm. long, described by Thompson, the allan- EARLY HUMAN EMBRYOS AND THEIR MEMPRANES 77 tois has elongated and shows three irregular dilatations (Fig. 80). A large cavity never appears distally in the human allantois as in Ungulates. When it becomes included in the umbilical cord its distal portion is tubular and it eventually atro- phies. That part of the allantois extending from the umbilicus to the cloaca of the hind-gut possibly takes part in forming the bladder and the wrachus, a rudiment extending as a solid cord from the fundus of the bladder to the umbilicus. The human allantois is thus small and rudimentary as compared with that of birds and Ungulates. As we have seen, the cavity is very large in the pig, and Haller found an allantoic sac two feet ee Ss . ae > long connected with a goat embryo of fi . \. two inches. In human embryos it ap- Pharynx-___..... Tm ‘ Pharyngeal f. MM ‘ Go, / membrane 7s \ oe Thyreoid \ } Pericardium | Hepatic diverticulum __ ; | Septum lransversum i j | Yolk-sac 4 | Cut edge of re | amnion Yolk stalk. Primitive Segments Allantois Cloacal membrane Cloaca _[, Neural folds wee — Neurenteric canal ay Fic. 80.—Median sagittal section of a 2.5 Fic. 81—Human embryo of 2.11 mm. (Eternod). mm. human embryo showing digestive tract xX 35. (after Thompson). X 40. pears very early and is not free, but embedded in the body stalk. Its func- tions, so important in birds and Ungulates, are in man performed by the chorion. Yolk Sac and Yolk Stalk.—In the youngest human embryos described, the entoderm forms a somewhat elongated vesicle (Fig. 76). With the development of the fore-gut and hind-gut in embryos of 1.54 and 2 mm. (Figs. 77 and 78), the entodermal vesicle is divided into the dorsal intestine and ventral yolk sac, the two being connected by a somewhat narrower region. This condition persists in an embryo 2.5 mm. long (Fig. 80). In the figure most of the yolk sac has been 78 THE FETAL MEMBRANES AND EARLY HUMAN EMBRYOS cut away. Embryos with 9 and 14 pairs of segments, with three brain vesicles and with the amnion cut away are seen in Figs. 81 and 324. The relation of the Amnion Fic. 82.—Human embryo of about 2.5 mm. (His, after Coste). 15. fetal appendages to the embryo shows well in the embryo of Coste (Fig. 82). The dorsal concavity is probably abnormal. A robust body stalk attaches the Amnion ———_~ & Mavillary process Branchial clefts 1-3 Mandibular process Heart CTERT IR Body stalk Yolk-sac Fic. 83.—Human embryo 2.6 mm. long showing amnion, yolk stalk and body stalk (His). 25. embryo to the inner wall of the chorion. With the growth of the head- and tail folds of the embryo, there is an apparent constriction of the yolk sac where it THE ANATOMY OF A 4.2 MM. HUMAN EMBRYO 79 joins the embryo. This will become more marked in later stages and form the yolk stalk. His’ embryo, 2.6 mm. long, shows the relative size of yolk sac and embryo and the yolk stalk (Fig. 83). The relations of the fetal membranes to the embryo are much the same as in the chick embryo of five days, save that the al- lantois of the human embryo is embedded in the body stalk. The embryo shows a regular convex dorsal curvature, there is a marked cephalic bend in the region of the mid-brain and there are three gill clefts. The head is twisted to the left, the tail to the right. At the side of the oral sinus are two large processes; the dorsal of these is the maxillary, the ventral the mandibular process. The heart is large and flexed in much the same way as the heart of the fifty-hour chick embryo. In later stages, with the development of the umbilical cord, the yolk stalk becomes a slender thread extending from the dividing line between the fore- and hind-guts to the yolk sac or umbilical vesicle (Figs. 84 and 119). It loses its at- tachment to the gut in 7mm. embryos. A blind pocket may persist at its point of Fic. 84.—Yolk sac and stalk of a20 mm. humanembryo. X 11. union with the intestine and is known as Meckel’s diverticulum, a structure of clinical importance because it may telescope and cause the occlusion of the intes- tinal lumen. The yolk stalk may remain embedded in the umbilical cord and extend some distance to the yolk sac which is found between the amnion and chorion. The yolk sac may be persistent at birth. THE ANATOMY OF A 42 MM. HUMAN EMBRYO This embryo, studied and described by His, is regarded by Keibel as not quite normal. Viewed from the left side (Fig. 85), with the amnion cut away close to its line of attachment, there may be seen the yolk stalk, and a portion of the yolk sac and of the body stalk. There is an indication of the primitive segments along the dorso-lateral line of the trunk. The head is bent ventrad almost at right angles in the mid-brain region (cephalic flexure). There are also marked cervical and caudal flexures, the trunk ending in a short blunt tail. The heart is large and 80 THE FETAL MEMBRANES AND EARLY HUMAN EMBRYOS flexed as in the earlier stage. Three gill clefts separate the four branchial arches. The first has developed two ventral processes. Of these, the maxillary process is small and may be seen dorsal to the stomodeum. The mandibular process is large and has met its fellow of the right side to form the mandible or lower jaw. Dorsal to the second gill cleft may be seen the position of the oval olocyst, now a closed sac. Opposite the atrial portion of the heart, and in the region of the caudal flexure, bud-like outgrowths indicate the anlages of the upper and lower extremities. Central Nervous System and Sense Organs.—The neural tube is closed throughout its extent and is differentiated into brain and spinal cord. The brain tube, or excephalon, is divided Mid-brain 2 Horie by constrictions into four regions, or 5 ; ‘ ' ‘Povecbraia v4 a Auditory vesic vesicles, as in the fifty-hour chick d C \ (Fig. 57). Of these, the most ceph- Stomod: Pe 3 i : : Ue Ee Ly y a "iia alad is the felencephalon. It is a Mandibular a fe, A » od he " - rote hig paired outgrowth from the fore-brain, Heart seal the persisting portion of which is the diencephalon. The mid-brain or mesencephalon, located at the cephalic flexure, is not subdivided. The hind- brain, or rhombencephalon, which is Amnion (cut) long and continuous with the spinal cord, later is subdivided into the metencephalon (region of the cere- fs Body stalk bellum and pons) and myelencephalon The cord forms a closed tube extending Fic. 85.—Left side of a human embryo of 4.2 mm. co. ee (medulla oblongata). spinal from the brain to the tail and containing the neural cavity, flattened from side to side. The eye is represented by the optic vesicles and the thickened ectodermal anlage of the lens. Its stage of development is between that of the thirty-six and fifty-hour chick embryos. The olocyst is a closed sac, no longer connected with the outer ectoderm as in the fifty-hour chick. Digestive Canal.—In a reconstruction of the viscera viewed from the right The pharvn- geal membrane, which we saw developed in the chick between the stomodeum side (Fig. 86), the entire extent of the digestive canal may be seen. THE ANATOMY OF A 4.2 MM. HUMAN EMBRYO 81 and the pharynx, has broken through so that these cavities are now in communi- cation. The fore-gut, which extends from the oral cavity to the yolk stalk, is differentiated into pharynx, thyreoid, trachea and lungs, esophagus and stomach, small intestine and digestive glands (pancreas and liver). The gut is suspended from the dorsal body wall by the dorsal mesentery. Mesencephalon and cephalic flexure Hy pophysis Diencephalon Internal carotid artery Atrium of heart _Umbilical vein Liver anlage Splanchnic mesoderm -Mid-gut Entoderm of yolk stalk Tail gut Umbilical artery Mesone phric duct Allantois Fic. 86.—Diagrammatic reconstruction of a 4.2 mm. human embryo, viewed from the right side (adapted froma model by His). X 25. The ectodermal limits of the oral cavity are indicated dorsad by the diver- ticulum of the hypophysis (Rathke’s pocket). The fore-gut proper begins with a shallow out-pocketing known as Seessel’s pocket. As the pharyngeal’ mem- brane disappears between these pockets, it would seem that Seessel’s pocket represents the persistence of the blind anterior end of the fore-gut. No other significance has been assigned to it. The pharynx is widened laterally and at this stage shows four pharyngeal 6 82 THE FETAL MEMBRANES AND EARLY HUMAN EMBRYOS pouches (Fig. 87). Later a fifth pair of pouches is developed (Fig. 168). The four pairs of pharyngeal pouches are important as they form respectively the following adult structures: (1) the auditory tubes; (2) the palatine tonsils; (3) the thymus anlages; (4) the parathyreoids or epithelial bodies. Between the pharyn- geal pouches are the five branchial arches in which are developed five pairs of aortic arches. Between the bases of the first and second branchial arches, on Mouth cavity Thyreoid anlage Pharyngeal pouches 1-4 Trachea ‘Lung bud Stomach Hepatic diverticulum Dorsal pancreas Ventral pancreas Yolk stalk Mesonebhric tubule with glomerulus Hind-gul Ht— Mesonephros Allgatoss Mesonephric duct Fic. 87.—Diagrammatic ventral view of pharynx, digestive tube, and mesonephroi of a 4-5 mm. embryo (based on reconstructions by Grosser and His). > about 30. The liver and yolk sac are cut away. The tubules of the right mesonephros are shown diagrammatically... the floor of the pharynx, is developed the tuberculum impar which perhaps forms a portion of the anterior part of the tongue. Posterior to this unpaired anlage of the tongue there grows out ventrally the anlage of the thyreoid gland. From the caudal end of the trachea have appeared ventrally the lung buds. The trachea is still largely a groove in the ventral wall of the pharynx and esophagus (Fig. 86). Caudal to the lungs a slight dilation of the digestive tube indicates the position of the stomach. The liver diverticulum has grown out from the fore-gut Aortic arches 1-4 Atrium Vitello-umbilical vein Liver | a L. umbilical vein | R. vitelline vein | I\\ i ~ Common cardinal vein - Vitelline vein —-—-Umbilical vein Placental attachment Fic. 89.—Lateral view of human embryo of 4.2 mm., showing aortic arches and venous trunks (His). mx, Maxillary process; jv., anterior cardinal vein; c.v., posterior cardinal vein; of, otocyst. THE ANATOMY OF A 4.2 MM. HUMAN EMBRYO 83 into the ventral mesentery cranial to the wall of the yolk stalk. It is much larger than in the fifty-hour chick, where its paired anlage was seen cranial to the fovea cardiaca, and is separated from the heart by the septum transversum. The small intestine between the liver and yolk stalk is short and broad. In later stages it becomes enormously elongated as compared with the rest of the diges- tive tube. The yolk stalk is still expansive. The region of its attachment to the gut corresponds to the open mid-gut of the chick embryo. The hind-gut and tail fold of this embryo are greatly elongated as compared with the chick embryo of fifty hours. The hind-gut terminates blindly in the tail. Near its caudal end it is dilated to form the cloaca. Into the ventral side of the cloaca opens the stalk of the allantois. Dorso-laterally the primary excretory (Wolffian) ducts ) which we saw developed in the fifty-hour chick have connected with the cloaca and open into it. Caudal to the cloaca, on thé ventral side, is the cloacal mem- brane, which later divides and breaks through to form the genital aperture and anus. That part of the hind-gut between the cloaca and the yolk stalk forms the rectum, colon, cecum, and appendix, with a portion of the small intestine (ileum). Urogenital Organs.—The opening of the primary excretory (Wolffian) ducts into the cloaca has been noted. These are the ducts of the mid-kidney or mesonephros. At this stage the nephrotomes, which in the chick embryos formed the anlages of these ducts, are also forming the kidney tubules of the meso- nephros which open into the ducts (Fig. 87). The mid-kidneys project into the peritoneal cavity as ridges on each side. A thickening of the mesothelium along the median halves of the mesonephroi forms the anlage of the genital glands or gonads (Fig. 220). Circulatory System.—The /eart is an S-shaped double tube as in the fifty- hour chick. The outer myocardium is confined to the heart while the inner endothelial layer is continuous, at one end with the veins, at the other end with the arteries. The disposition of the heart tube is well seen in a ventral view of a younger embryo (Fig. 88). The veins enter the sinus venosus just cranial to the yolk sac. Next in front is the afrium with the convexity of its flexure di- rected cephalad. The ventricular portion of the heart is U-shaped and is flexed to the right of the embryo. The left limb is the ventricle, the right the bulbus. The arteries begin with the ventral aorta which bends back to the midline and divides into five branches on each side of the pharynx (Figs. 88 and 89). These are the aortic arches and they unite dorsally to form two trunks, the descending aorie. ‘The aortic arches pass around the pharynx between the gill clefts in the 84 THE FETAL MEMBRANES AND EARLY HUMAN EMBRYOS Frc. 90.—Embryos of the first six weeks (2.1 to 11 mm.). x 3. From His’ Normentafel (Keibel and Elze). THE ANATOMY OF A 4.2 MM. HUMAN EMBRYO 85 branchial arches. The arrangement is like that of the adult fish which has gill slits, branchial arches, and aortic arches to supply the gills. The descending 4 L By Eb TRE, ek f Frc. 91.—Embryos of six to eight weeks (12.5 to 23 mm.). From His’ Normentafel (Keibel and Elze). X 2.5. Stage w(22) marks the transition from embryo to fetus. aorte run caudad and opposite the lung buds unite to form a single median dorsal aorta. This, in the region of the posterior limb buds, divides into the two um- 86 THE FETAL MEMBRANES AND EARLY HUMAN EMBRYOS bilical arteries, which, curving cephalad and ventrad, enter the body stalk on each side of the allantois and eventually ramify in the villi of the chorioa. The vilelline arteries, large and paired in the chick, are represented by a single small trunk which branches on the surface of the yolk sac (Fig. 271). Compared with the arterial circulation of the chick of fifty hours the important differences are (1) the development of the fourth and the fifth pairs of aortic arches, and (2) the presence of the chorionic circulation by way of the umbilical] arteries in addi- tion to the vitelline circulation found in the fifty-hour chick. The veins are all paired and symmetrically arranged (Figs. 88 and 279). There are three sets of them: (1) The blood from the body of the embryo is drained, from the head end by the anterior cardinal veins; from the tail end of the body by the posterior cardinal veins. These veins on each side unite dorsal to the heart and form a single common cardinal vein which receives the vitelline and umbilical veins of the same side before joining the heart. (2) Paired vitelline veins in the early stages of the embryo drain from the yolk sac the blood carried to it by the vitelline arteries. The trunks of these veins pass back into the body on each side of the yolk stalk and liver, and with the paired umbilical veins form a trunk which empties into the sinus venosus of the heart. As the liver develops it may be seen that the vitelline veins break up into blood spaces called by Minot sinusoids (Fig. 279). When the liver becomes large and the yolk sac rudimentary the vitelline veins receive blood chiefly from the liver and intestine. (3) A pair of large umbilical veins which drain the blood from the villi of the chorion and are the first veins to appear. These unite in the body stalk, and, again separating, enter the somatopleure on each side. They run cephalad to the septum trans- versum where they unite with the vitelline veins to form a common vitello-umbil- ical trunk which joins the common cardinal and empties into the sinus venosus. The veins of this embryo are thus like those of the fifty-hour chick save that the umbilical vessels are now present and take the place of the allantoic veins of later chick embryos. The veins, like the heart and arteries, are primitively paired and symmetrically arranged. As development proceeds, their symmetry is largely lost and the asymmetrical venous system of the adult results. The later stages of the human embryo cannot be described in detail here. The student is referred to the texts of Minot, and Keibel and Mall. Two embryos will be compared with the pig embryos described in Chapter V. Figs. 90 and 91 show the human embryos described by His, the ages of which were estimated by him at from two weeks to two months. The figures show as well as could any description the changes which lead to the adult form when the embryo may be THE AGE OF HUMAN EMBRYOS 87 called a fetus (stage w). The external metamorphosis is due principally: (1) to changes in the flexures of the embryo; (2) to the development of the face; (3) to the development of the external structure of the sense organs (nose, eye, and ear); (4) to the development of the extremities and disappearance of the tail. The more important of these changes will be dealt with in later chapters. THE AGE OF HUMAN EMBRYOS The ages of the human embryos which have been obtained and described can- not be determined with certainty, because fertilization does not necessarily fol- low directly after coitus. It has been shown also that ovulation does not always coincide with menstruation so that the menstrual period cannot be taken as the starting point of pregnancy. In 1868, Reichert, from studying the corpus luteum in ovaries obtained during menstruation, concluded that ovulation takes place as a rule just before menstruation and that if the ovum is fertilized the approaching menstruation does not occur. Reichert then decided that a human embryo of 5.5 mm., which he had obtained from a woman two weeks after menstruation failed to occur, must be two weeks, not six weeks, old. His accepted Reichert’s views and since then the ages of embryos have largely been estimated on this basis. Ac- cording to this view, Peter’s ovum, obtained thirty days after the last period, is only three or four days old. This does not agree at all with what is known of the age of other mammalian embryos. From the observations of Mall and obstetricians of the present day, we must conclude that ovulation does not immediately precede menstruation, but that most pregnancies take place during the first or second week after the menstrual period. It is therefore more correct to compute the age of the embryo from the end of the last menstruation, or, according to Grosser, from the tenth to the twelfth day before the first missed menstrual period. Peter’s embryo then would be about fifteen days old. To compare an embryo with one of known age, the crown-rump length (i. e., from vertex to breech) is usually taken. Embryos of the same age vary greatly in size so that their structure must be taken into account. At the present time the exact relation of ovulation to menstruation is not known, nor the exact time required for the fertilized ovum to reach the uterus. The computed age of the embryo thus can be only approximate. The period of gestation of the human fetus is usually computed from the beginning of the last menstrual period. Forty weeks or two hundred and eighty days is the time usually allowed. As some women menstruate once or more after becoming pregnant this is not a certain basis for computation. 88 THE FETAL MEMBRANES AND EARLY HUMAN EMBRYOS The following are the estimated ages and lengths of human embryos, accord- ing to Mall, and their weights, according to Fehling: Crown-HEEL LENGTH CROWN-RUMP LENGTH WEIGHT AGE. (CH), or STANDING (CR), or SITTING IN HEIGHT (MM.). HEIGHT (MM.). Grams. Twenty-one days..............-0.0000 0.5 0.5 Twenty-eight days..................00. 2.5 2.5 Thirty-five days..............-...-00005 5:5 5:5 Porty=twodaySir.o1-on aise weaned ans 11.0 11.0 Forty-nine days iisnysxaase eae a qnteenetels 19.0 17.0 Second lunar month.................... 30.0 25.0 es Third dunar monthi.. 2.03 eeecn2ee 4 cases 98.0 68.0 20 Fourth lunar month.................... 180.0 121.0 120 Fifth lunar month...................... 250.0 167.0 285 Sixth lunar month. ..................... 315.0 210.0 635 Seventh lunar month................... 370.0 245.0 1220 Fighth lunar month.................... 425.0 284.0 1700 Ninth lunar month................00... 470.0 316.0 2240 Tenth lunar month..................... 500.0 345.0 3250 Wee CHAPTER V THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS A. THE ANATOMY OF A SIX MM. PIG EMBRYO VERY young pig embryos of the primitive streak and neural fold stages have been seen already (Fig. 26). In its early stages the pig embryo is flattened out on the surface of the yolk sac like a chick embryo (Fig. 92), but as the head and tail folds elongate the body becomes B flexed and twisted spirally, making it difficult to study. In embryos 5 to 7 mm. long the twist of the body ye } begins to disappear and its structure Wy may be seen to better advantage. External Form of 6 mm. Em- bryo.—When compared with the form of the 4 mm. human embryo, the marked difference in the 6 mm. pig is the convex dorsal flexure which brings the head and tail regions close together (Fig. 93). The ceph- alic flexure at the mesencephalon forms an acute angle and there is a marked neck or cervical flexure. As a result, the head is somewhat tri- See ae Fic. 92.—Pig embryos (A) of seven and (B) of dorsad in an even convex curve _ eleven primitive segments, in dorsal view with amnion and the tail is flexed sharply dorsad. ‘Yt *¥4Y (Aerbel, Nemmentatel). 2, 20) Lateral to the dorsal line may be seen the segments, which become larger and more angular in form. The body is bent differentiated from tail to head. At the tip of the head a shallow depression marks the anlage of the olfactory pit. The lens vesicle of the eye is open to the exterior. Caudal to the eyes at the sides of the head are four branchial arches separated by three grooves, the branchial clefts. The fourth arch is partly concealed in a tri- 89 go THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS angular depression, the cervical sinus, formed by the more rapid growth of the first and second arches (cf. Fig. 97). The first, or mandibular arch, forks ventrally into two processes, a smaller maxillary and a larger mandibular process, and the latter with its fellow forms the mandible or lower jaw. The position of the mouth is indicated by the cleft between these processes. The groove between the eye and the mouth is the lacrimal groove. The second or hyoid arch is separated from the mandibular arch by a hyo- mandibular cleft which persists as the external auditory meatus. About the dorsal end of the cleft develops the external ear. Maxillary process Mandibular process \ Branchial arch 2 Coppa Branchial arch 3 Cervical sinus Atrium of heart Olfactory pil —— ; A c iy \ a, Liver ey 3 4h, Yolk suey are ha 4 os Sn fr ia \ a LU pper limb bud a) Fic. 93.—Pig embryo of 6 mm., viewed from the left side. The amnion has been removed and its cut edge is shown in the figure. X 12. The heart is large and through the transparent body wall may be seen the dorsal atrium and ventral ventricle. Caudal to the heart a convexity indicates the position of the diver. Dorsal to the liver is the bud of the anterior extremity, now larger than in the 4mm. human embryo. Extending caudal to the anlage of the upper extremity a curved convexity indicates the position of the left” mesonephros. At its caudal end is the bud of the lower limb. The amnion has been dissected away along the line of its attachment ventral to the mesonephros. There is as yet no distinct umbilical cord and a portion of the body stalk is attached to the embryo. Due to a shorter term of development, a young pig embryo is somewhat pre- THE ANATOMY OF A SIX MM. PIG EMBRYO gt cociously developed in comparison with a human embryo ot the same size (Fig. 94). Ina human embryo 7 mm. long the head is larger, the tail shorter. The Myelence phalon Ugg AIS HD ya “= Metencephalon S . ( al Spinal cord— tN SOx d 1 Y $ Fire Cervical segment § E WOH, yor Future milk line Yolk sac ana umbilical cord Lumbar segment 5 Fic. 94.—A human embryo 7 mm. long, viewed from the right side (Mall in Kollmann). xX 14. I, II, IIT, Branchial arches 1, 2, and 3; H, Ht, heart; L, liver; L’, otic vesicle; R, olfactory placode; Tr, semilunar ganglion of trigeminal nerve. cervical flexure is more marked, the olfactory pits larger and deeper. ‘The liver is more prominent than in the 6 mm. pig, the mesonephros and segments less so. DISSECTIONS OF THE VISCERA To understand the sectional anatomy of an embryo, a study of dissections and reconstructions is essential. For methods of dissection see p. 137, Chapter VI. Before studying sections, the student should become as well acquainted as possible with the anatomy of the embryo and compare each section with the figures of reconstructions and dissections. Nervous System.—Fig. 95 shows the central nervous system and viscera exposed on the right side of a 5.5 mm. embryo. The ventro-lateral wall of the head has been left intact with the lens cavity, olfactory pit, and portions of the Qg2 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS maxillary and mandibular processes, second and third branchial arches, and cervical sinus (cf. Fig. 93). The brain is differentiated into the five regions, telencephalon, diencephalon, mesencephalon, metencephalon, and myelencephalon. The spinal cord is cylindrical and gradually tapers off to the tail. The anlages of the cerebral and spinal ganglia and the main nerve trunks are shown. The oculomotor nerve begins to appear from the ventral wall of the mesencephalon. Sup. gang.n.9g Oltocyst Acoustic ganglion Jugular gang. n. 10 Geniculate gang. n.7 Gang. nodosum n. 10 N. accessorius Semilunar gang. n. 5 Melencephalon Gang. cerv. I hi i - aa ) / Qo tresorceptaton N. hypoglossus Lif Cervical sinus Diencephalon Petrosal gang. vn. 0 Lens opening : Olfactory pit a RS actor pt Dorsal lobe liver— ee Paget si ee a4 Telencephalon s , . y : i = NR! —_ Yolk sac t } PN Ventral lobe liver — Allantots Veniricle Small intestine NS : Allantoic stalk Hind-gut Fic. 95.—Dissection of a 5.5 mm. pig embryo, showing the nervous system and viscera from the right side. X 18. Ventro-lateral to the metencephalon and myelencephalon occur in order the semilunar ganglion and three branches of the trigeminal nerve; the geniculate ganglion and nerve trunk of the n. facialis; the ganglionic anlage of the ”. acusticus and the ofocyst. It will be observed that the nerve trunks are arranged with reference to the branchial arches and clefts. Caudal to the otocyst'a continuous. chain of cells extends lateral to the neural tube into the tail region. Cellular THE ANATOMY OF A SIX MM. PIG EMBRYO 93 enlargements along this neural crest represent developing cerebral and spinal ganglia. They are in order the superior or root ganglion of the glossopharyngeal nerve with its distal petrosal ganglion; the ganglion jugulare and distal ganglion nodosum of the vagus nerve; the ganglionic crest and the proximal portion of the spinal accessory nerve; and the anlage of Froriep’s ganglion, an enlargement on the neural crest just cranial to the first cervical ganglion. Between the vagus and Froriep’s ganglion may be seen the numerous root fascicles of the hypoglossal nerve, which take their origin along the ventro-lateral wall of the myelencephalon and unite to form a single trunk. The posterior roots of the spinal ganglia are very short; their anterior or ventral roots are not shown. The position of the heart with its ventricle, atrium, and sinus venosus are shown. The diver is divided into a small dorsal and a large ventral lobe. The fore-gut emerges from between the liver lobes and curves ventrad to the yolk stalk and sac. The hind-gut is partly hidden by the fore-gut; it make a U- shaped bend from the yolk stalk to the caudal region. The gut is attached to the dorsal body wall by a double layer of splanchnic mesoderm which forms the mesentery. ‘The long, slender mesonephros lies ventral to the spinal cord and curves caudad from a point opposite the eighth cervical ganglion to the tail re- gion. The cranial third of the mesonephros is widest and its size diminishes tailwards. Between the yolk sac and the tail the allantois is seen, its stalk curving around from the ventral side of the tail region. Digestive Canal.—The arrangement of the viscera may be seen in median sagittal and ventral dissections (Figs. 96 and 97), also in the reconstruction shown in Fig. 105. The mouth lies between the mandible, the median fronto- nasal process of the head, and the maxillary processes at the sides. The divertic- ulum of the hypophysis (Rathke’s pocket), flattened cephalo-caudad and expanded laterad, extends along the ventral wall of the fore-brain (Fig. 105). Near its distal end, the wall of the brain is thickened and later the posterior lobe of the hypophysis will develop from the brain wall at this point. The pharynx is flattened dorso-ventrally and is widest near the mouth. Its lateral dimension narrows caudad, and opposite the third branchial arch it makes an abrupt bend, a bend which corresponds to the cervical flexure of the embryo’s body (Figs. 104 and 105). In the roof of the pharynx, just caudal to Rathke’s pocket, is the somewhat cone-shaped pouch known as Seessel’s pocket, which may be interpreted as the blind cephalic end of the fore-gut. The lateral and ven- tral walls of the pharynx and oral cavity are shown in Fig. 98. Of the four arches the mandibular is the largest and a groove partly separates the processes of the 94 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS two sides. Posterior to this groove and extending in the median line to the hyoid arch is a triangular rounded elevation, the tuberculum impar, which later forms a small part of the tongue. At an earlier stage the median thyreoid anlage grows out from the mid-ventral wall of the pharynx just caudal to the tuberculum impar. The ventral ends of the second arch fuse in the mid-ventral line and form a prominence, the copula. This connects the tuberculum impar with a Pharynx Neuromere 4 Rathke’s pocket Anlage of tongue I. sthmus AMesencephalon R. atrium Se Esophagus —~__ Diencephalon Interatrial ( ; Ma\ 5,’ ne , — Bulbus cordis foramen | a aa a Lung bud | aa ae) Os Be ~~ ——— Telencephalon Stomach MBNA! \t ; Ventricle Hepatic ~~ Septum trans- diverticulum versumt Ventral Liver ancreas P Yolk sac Allantois Cranial limb 3 intestine j Poa gut Cloaca L. genital fold Metanephros Spinal cord os Caudal limb of intestine R. mesone phros Mesonephric duct Fic. 96.—Median sagittal dissection of a pig embryo of 6 mm., to show viscera and neural tube. X 18. rounded tubercle derived from the third and fourth pairs of arches, the anlage of the epiglottis. Its cephalic portion forms the root of the tongue (Fig. 156). Caudal to the epiglottis are the arytenoid ridges, and a slit between them, the glottis, leads into the trachea. The branchial arches converge caudad and the pharynx narrows rapidly before it is differentiated into the trachea and esophagus (Figs. 104 and 105). THE ANATOMY OF A SIX MM. PIG EMBRYO 95 Laterally and ventrally. between the arches are the four paired outpocketings of the pharyngeal pouches. The pouches have each a dorsal and ventral divertic- ulum (Fox, Thyng). The dorsal diverticula are large and wing-like (Fig. 104); they meet the ectoderm of the gill clefts and fuse with it to form the closing plates. Between the ventral diverticula of the third pair of pouches lies the median thy- reoid anlage. The fourth pouch is smaller than the others. Its dorsal diverticu- a ronto-nasal process Olfactory pit Maxillary process Mandibular process Mouth Branchial arch 2 Branchial arch 3 Aortic bulb Branchial arch 4 Upper limb bud Hepatic diverticulum Yolk sac Body stalk Allantois Umbilical arlery ,__———“er aN VP wy Lower limb bud Mesonephric duct eas ee Dorsal aorta and umbilical artery Rectum Fic. 97.—Ventral dissection of a 6 mm. pig embryo. X 14. The head has been bent dorsally. lum just meets the ectoderm; its ventral portion is small, tubular in form, and is directed parallel to the esophagus (Fig. 104). The groove on the floor of the pharynx caudal to the epiglottis is continu- ous with the tracheal groove. More caudally, opposite the atrium of the heart, the trachea has separated from the esophagus (Fig. 96). The trachea at once bifurcates to form the primary bronchi and the anlages of the lungs (Fig. 97). The lungs consist merely of the dilated ends of the bronchi surrounded by a layer of splanchnic mesoderm. They bud out laterally on each side of the esophagus 96 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS near the cardiac end of the stomach, and project into the pleural cwlom. The esophagus is short and widens dorso-ventrally to form the stomach. The long axis of the stomach is nearly straight, but its entodermal walls are flattened together and it has revolved on its long axis so that its dorsal border lies to the left, its ventral border to the right, as seen in transverse section (Fig. 111). Caudal to the pyloric end of the stomach, and to its right, is given off from the duodenum the hepatic diverticulum. Its opening into the gut is seen in the ventral dissection (Fig. 97). The hepatic diverticulum is a sac of elongated oval form from which the liver and part of the pancreas take origin, and which later gives rise to the gall bladder, cystic duct, and common bile « duct. ti is connected by several cords of cells with the trabeculz of the liver. The liver is divided incompletely into four lobes, a small dorsal and a large ventral lobe on each side (Figs. 95 and 112). The lobation does not show in a Branchial arch I ‘ f Lateral lingual anlage \ ye Y f Tuberculum impar —~———_ > Branchial arch II Branchial arch III Branchial arch IV Glottis Epiglottis Arylenoid ridge Fic. 98.—Dissection of the tongue and branchial arches of a 7 mm. pig embryo, seen in dorsal view. X 15. median sagittal section. The pancreas is represented by two outgrowths. The ventral pancreas originates from the hepatic diverticulum near its attachment to the duodenum (Fig. 96). It_grows to the right of the duodenum and-ventral to the portal vein. The dorsal pancreas takes origin from the dorsal side of the duodenum caudal tothe hepatic diverticulum and grows dorsally into the sub- stance of the gastric mesentery (Figs. 105 and 113). It is larger than the v entral pancreas, and its posterior lobules grow to the right and dorsal to the portal vein and in later stages anastomose with the lobules of the ventral pancreas. The intestine of both fore-gut and hind-gut has elongated and curves ven- trally into the short umbilical cord where the yolk stalk has narrowed at its point of attachment to the gut (Fig. 96). As the intestinal tube grows ventrad, the layers of splanchnic mesoderm which attach it to the dorsal body wall grow at an equal rate and persist as the mesentery. THE ANATOMY OF A SIX MM. PIG EMBRYO 97 The cloaca, a dorso-ventrally expanded portion of the hind-gut, gives off cephalad and ventrad the allantoic stalk. This is at first a narrow tube, but soon expands into a vesicle of-large size, a portion of which is seen in Fig. 95. Dorso- laterad the cloaca receives the primary excretory (mesonephric) ducts. The hind- gut is continued into the tail as the tail gut (postanal gut) which dilates at its ex- tremity as in the 7.8 mm. pig described by Thyng. The mid-ventral wall of the cloaca is fused to the adjacent ectoderm to form the cloacal membrane. In this region later the anus arises (Fig. 105). The postanal gut soon disappears. Urogenital System.—This consists of the mesonephroi, the mesonephric (Wolf- fian) ducts, the anlages of the metanephrot, the cloaca, and the allantois. The form of the mesonephroi is seen in Figs. 95 and97. Each consists of large vascular glom- eruli associated with coiled tubules lined with cuboidal epithelium and opening into the mesonephric duct (Figs. 114 and 208). The Wolffian ducts, beginning at the anterior end of the mesonephros, curve at first along its ventral, then along Bulbus cordis its lateral surface. At its caudal end AGL. atrium each duct bends ventrad and to the mid- line where it opens into a lateral expansion of the cloaca (Fig. 96). Before this junc- tion takes place, an evagination into the 'L. ventricle mesenchyme from the dorsal wall of each Fic. 99.—Ventral and cranial surface of the mesonephric duct gives rise to the anlages heart from a 6 mm. pig embryo. xX 14. of the metanephroi, or permanent kid- neys. A slight thickening of the mesothelium along the median and ventral sur- face of each mesonephros forms a light-colored area, the genital fold (Fig. 96). This area is pointed at either end and confined to the middle third of the kidney. It is the anlage of the genital gland from which either testis or ovary is developed. Blood Vascular System.—The /eart lies in the pericardial cavity, as seen in Fig. 96. The atrial region (Fig. 99), as in the 4.2 mm. human embryo, has given rise to two lateral sacs, the right and left atria. The bulbo-ventricular loop has become differentiated into right and left ventricles much thicker walled than the atria. The right ventricle is the smaller and from it the bulbus passes be- tween the atria and is continued as the ventral aorta. Viewed from the caudal and dorsal aspect (Fig. 100) the szus venosus is seen dorsal to the atria. It opens into the right atrrum and receives from the right side the right common cardinal vein, from the left side the left common cardinal. These veins drain the blood from the body of the embryo. Caudally the sinus’ venosus receives the two 7 98 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS vitelline veins. Of these, the left is small in the liver and later disappears. The right vitelline vein, now the common hepatic, carries most of the blood to the heart from the umbilical veins, and from the liver sinusoids, gut, and yolk sac. Transverse sections of the embryo through the four chambers of the heart show the atria in communication with the ventricles through the atrie-ventricular ee ( See 7 — Bulbus cordis See A. comin Se es y, XS R. atrium cardinal vein / ¥ OG fe \ Soe. % L. common i = in . cardinal vein “S28 y L. vitelline vein —+—- 3 —R. vilelline vein } Left ventricle —— ——R, ventricle Fic. 100—Dorsal and caudal view of the heart from a 6 mm. pig embryo. X 21. foramina, and the sinus venosus opening into the right atrium (Fig. 109). This opening is guarded by the right and left valves of the sinus venosus. Septa in- completely separate the two atria and the two ventricles. In Fig. 109 the atrial septum (sepium primum) appears complete due to the plane of the section. In Fig. 101, from a slightly smaller embryo, it is seen that the sepium primum grows from the dorsal atrial wall Bulbus cordis eee of the heart and does not yet s<—loramen ovale 7 Wall of 1. atrium meet the endocardial cushions be- “1 nteratrial oramen : : Z oe cushions tween the atrio-ventricular canals. R. ventricle-fy Interventricular¢ foramen This opening between the atria is Wall of 1. ventricle . ; known as the iuteratrial foramen. Before it closes, another opening Fic. 101.—Dissection of a 5.5 mm. pig’s heart appears in the septum, dorsal in from the left side, showing the septum primum and dae ae at the interatrial and oval foramina. X 14. position. This is the foramen ovale and persists during fetal life. In Fig. 101 these two openings may be seen, as may also the dorsal and ventral endocardial cushions which bound the atrio-ventricular foramina. The outer mesothelial layer of the ventricles has become much thicker than that of the atria. It forms the epicardium and the myocardium, the sponge-like meshes of which are now being developed. THE ANATOMY OF A SIX MM. PIG EMBRYO 99 The Arteries.—These begin with the ventral aorta, which takes origin from the bulbus cordis. F ‘rom the ventral aorta are given off five pairs of aortic arches. These run dorsad in the five branchial arches (Figs. 104 and 105) and join the paired dorsal or descending aorte. The first and second pairs of aortic arches are very small and take origin from the small common trunks formed by the bifurca- tion of the ventral aorta just caudal to the median thyreoid gland. The fourth aortic arch is the largest. From the fifth arch small pulmonary arteries are devel- oping. There is evidence that this pulmonary arch is really the sixth in the series, the fifth having been suppressed in development (cf. Fig. 272 B). Cranial to the first pair of aortic arches, the descending aorte are continued forward into the maxillary processes as the internal carotids. Caudal to the aortic arches the descending aorta « converge, unite opposite the cardiac end of the stomach, and form the median dorsal aorta. From this vessel and from the descending aorte paired dorsal intersegmental arteries arise. From the seventh pair of these arteries (the first pair to arise from the medial dorsal aorta) there are developed a pair of lateral branches to the upper limb buds. These vessels are the sub- clavian arteries. From the dorsal aorta there are also given off ventro-lateral arteries to the glomeruli of the mesonephros, and median ventral arteries. Of the latter the celiac artery arises opposite the origin of the hepatic diverticulum. The vitelline artery takes origin by two or three trunks caudal to the dorsal pancreas. Of Of these trunks the posterior is the larger and persists as the superior mesenteric artery. Thyng (Anat. Record, vol. 5, 1911) has figured three trunks of origin in the 7.8 mm. pig. These unite and the single vitelline artery branches in the wall of the yolk sac. Opposite the lower limb buds the dorsal aorta is divided for a short distance. From each division there arises laterad ‘three short trunks which unite to form the single umbilical artery on each side. The middle vessel is the largest and appa- rently becomes the common iliac artery. A pair of short caudal arteries, much smaller in size, continue the descending aorte into the tail region. The Veins.—The vitelline veins, originally paired throughout, are now repre- sented distally by a single vessel, which, arising in the wall of the yolk sac, enters the embryo and courses cephalad of the intestinal loop (Fig. 102). Crossing to the left side of the intestine and ventral to it, it is joined by the superior mesenteric vein which has developed in the mesentery of the intestinal loop. The trunk formed by the union of these two vessels becomes the portal vein. It passes along the left side of the gut in the mesentery. Opposite the origin of the dorsal pan- creas it gives off a small branch, a rudimentary continuation of the left vitelline 100 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS vein, which courses cephalad and in earlier stages connects with the sinusoids of the liver. The portal vein then bends sharply to the right, dorsal to the duo- denum, and, in the course of the right vitelline vein, passing between the dorsal and ventral pancreas to the right of the duodenum, it soon enters the liver and connects with the liver sinusoids. The portal trunk is thus formed by persisting portions of both vitelline veins, and receives a new vessel, the superior mesenteric vein. The middle portions of the primitive vitelline veins are connected with the Spinal cord Nolochord Ant. cardinal vein Pharynx Ant. cardinal vein Cervical sinus a < . ovr carvAly, Pericardial cavily- Pericardial Y cavily Left common cardinal vein Left horn of sinus venosus Atrial junction sinus venosus Sinus venosus Right vitelline vein Liver Large venous sinusoid of liver Left vilelline vein Duclus venosus Ant. limb bud Hepatic diverticulum (cut) Inf. vena cava Volk stalk Dorsal pancreas Portal vein Cephalic limb intestinal loop Right umbilical vein Left vitelline vein Common vitelline vein Left umbilical vein Vitelline artery : Sup. mesenteric vein Caudal limb intestinal loop : ea Le ft bili ti Right umbilical artery ane Post. limb bud Dorsal aorta Spinal cord Fic. 102.—Reconstruction in ventral view of a 6 mm. pig embryo to show the vitelline and umbilical veins, the latter opened (original drawing by Dr. K. L. Vehe). > 22. In the small orientation figure (cf. Fig. 105) the various planes are indicated by broken lines—*------- --*, e network of liver sinusoids. Their proximal vitelline trunks drain the blood from the liver and open into the sinus venosus of the heart. The right member of this pair is much the larger (Fig. 100) and persists as the proximal portion of the infe- rior vena cava. For the development of the portal vein see Chapter IX. The umbilical veins, taking their origin in the walls of the chorion and allan- toic vesicle, lie caudal and lateral to the allantoic stalk and anastomose (Figs. 102 and 105). Before the allantoic stalk enters the body, the umbilical veins sepa- THE ANATOMY OF A SIX MM. PIG EMBRYO IOl rate and run lateral to the umbilical arteries. The left vein is much the larger. Both, after receiving. branches from the posterior limb buds and from the body wall, pass cephalad in the somatopleure at each side (Fig. 72). Their course is first cephalad, then dorsad, until they enter the liver. The left vein enters a wide channel, the ductus venosus, which carries its blood through the liver, thence to the heart by way of the right vitelline trunk. The right vein joins a large sinu- soidal continuation of the portal vein in the liver. This common trunk drains into the ductus venosus. Spinal cord Anterior cardinal vein Notochord Cervical sinus Pericardial cavity Evachea R. common cardinal vein L. common cardinal vein Lung Post. cardinal vein Eso phagus be live e Large venous sinusoid liver Stomach (cut edge) rior limb bud Anterior limb bu Omental bursa Inf. vena cava : . ; Mesogastrium Post. cardinal vein Mesonephros (cut surface) Mesonephros (cut surface) Capillary anastomosis between subcardinal veins Vitelline artery in dorsal mesentery Capillary anastomosis between subcardinal veins R. subcardinal vein Venous sinusoid on dorsum of mesonephros Venous sinusoid on dorsum of mesonephros Spinal cord Fic. 103.—Reconstruction of the cardinal and subcardinal veins of a 6 mm. pig embryo showing the early development of the inferior vena cava (Kk. L. Vehe). X 22. In the small orientation figure (cf. Fig. 105) the various planes are indicated by broken lines—*---------*. The anterior cardinal veins (Figs. 103 and 104) are formed to drain the plexus of veins on each side of the head. These vessels extend caudad and lie lateral to the ventral portion of the myelencephalon. Each anterior cardinal vein receives branches from the sides of the myelencephalon, then curves ventrad, is joined by the linguo-facial vein from the branchial arches and at once unites with the pos- terior cardinal of the same side to form the common cardinal vein. This, as we have seen, opens into the sinus venosus. 102 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS The posterior cardinal veins develop on each side in the mesonephric ridge, dorso-lateral to the mesonephros (Figs. 103, 104 and 112). Running cephalad, they join the anterior cardinal veins. When the mesonephroi become prominent, as at this stage, the middle third of each posterior cardinal is broken up into sinu- soids (Minot). Sinusoids extend from the posterior cardinal vein ventrally Int. car- Ant. car- Metencephalon otid artery dinal vein Thyreoid Ph. Pe ss M yelencephalon PUP Eg Mesence phalon Notochord Ventral aorla ‘f Descending aorta Ore | i : a — Se PhP Pulmonary artery Linguo-facial vein R. com. Nasal pil cardinal vein R. alrium R. ventricle Sinus venosus Com. hepatic vein Post. car- dinal vein R. subclavian vein R. subcar- dinal vein Pulmonary vein Intersegmental vein Spinal cord JLesone phros Post. cardinal vein Mesonephric arteries Fic. 104.—Reconstruction of 7.8 mm. pig embryo showing veins and aortic arches from the left side (after Thyng). X15. Ph. P. 1, 2, 3, 4, Pharyngeal pouches. around both the lateral and medial surfaces of the mesonephros. The median sinusoids anastomose longitudinally and form the subcardinal veins, right and left. The subcardinals lie along the median surfaces of the mesonephroi, more ventrad than the posterior cardinals with which they are connected at either end. There is a transverse capillary anastomosis between them, cranial and caudal to the THE ANATOMY OF A SIX MM. PIG EMBRYO 103 permanent trunk of the vitelline artery (Fig. 103). The right subcardinal is connected with the liver sinusoids through a small vein which develops in the mesenchyme of the plica ven cavee (caval mesentery) located to the right of the mesentery (Fig. 112). This vein now carries blood direct to the heart from the Aortic arch 1 Seessel’s pocket Aortic arch 2 ja sth mus Pharynx j ; Thyreoid Aortic arch 3 << w oo Int. carotid artery 106 Hypophysis (pharyngeal » Jobe) — AO RG FECES 107 ~ Telencephalon , Ventral aorta +— 1085 we Bulbus cordis Y— 109 : I nterventricular foramen Aortic arch 4 —4 I07 Aortic arch 5 and_{ pulmonary artery 7] I08 Esophagus LOY Linh 100 rach Bi ; Trachea He sy —-— L. horn of sinus venosus 110,_} | “fp— TIO L. umbilical vein R. ling ate hr ae ee Tail gut III—} I ——_ ae | Bb Volk sac (cut) 2s. _Cloaca | ose ru ie - PK ES 112 . Ii2 YN Spinal cord Stomach + ee) 113 4 17 ¥ 4 Hee oes 4 —~ Metanephric anlage Jee 7 Pi L. umbilical artery f~ - Anastomosis between dorsal aorle Allantoic stalk Ventral pancreas —® Dorsal Cee Gall bladder L. umbilical vein L. dorsal aorta Vitelline artery Mesonephric duct Cephalic limb of intestinal loop Artery to mesonephros Dorsal aorta Mesentery Caudal limb of intestinal loop Fic. 105.—Reconstruction of a 6 mm. pig embryo in the median sagittal plane, viewed from the The numbered heavy lines indicate the levels of the transverse sections shown in Figs. right side. 106-117. The broken lines indicate the outline of the left mesonephros and the course of the left um- The latter may be traced from the umbilical cord to the liver where it is sec- bilical artery and vein. tioned longitudinally. (Original drawing and reconstruction by Dr. K. L. Vehe). x 16.5. right posterior cardinal and right subcardinal, by way of the liver sinusoids and the right vitelline trunk (common hepatic vein). Eventually the unpaired inferior (For the development of the vena cava forms in the course of these four vessels. inferior vena cava see Chapter IX.) 104 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS TRANSVERSE SECTIONS OF A SIX MM. PIG EMBRYO Aaving acquainted himself with the anatomy of the embryo from the study or dissections and reconstructions, the student should examine serial sections cut in the plane indicated by guide lines on Fig. 105. Refer back to the external structure of the embryo (Fig. 93), to the lateral dissection of the organs (Fig. 95), and having determined the exact plane of each section, interpret the struc- _ tures seen by comparing with Fig. 105. The various structures may be recog- nized by referring to the figures of sections in the text, and they should be traced section by section through the series as carefully as time will allow. Remember that the sections of pig embryos figured here are drawn from the cephalic surface, so that the right side of the section is the left side of the embryo. Transverse Section through the Myelencephalon and Otocysts of a6 mm. Embryo (Fig. 106).—As the head is bent nearly at right angles to the body, this section passes length- Fourth ventricle Myelencephalon Neur. 6 Gang. superior n. 9 Ant. cardinal vein #-Gang. acust.n. 8 Neur. 3 ie Gang. geniculat, n. 7 Neur. 2- fg ; Neur. 1-* " Gang. semilunar. n. 5 Ant. cardinal vein Int. carotid artery ‘Ant. cardinal vein Dience phalon Fic. 106.—Transverse section through the myelencephalon and otocysts of a 6 mm. pig embryo. X 26.5. Gang. acust. n. 8, acoustic ganglion of acoustic nerve, etc.; Newr. 1-6, neuromeres 1-6. wise through the myelencephalon. The diencephalon is cut transversely. The cellular walls of the myelencephalon show a series of six pairs of constrictions, the neuromeres. Lateral to the fourth pair of neuromeres are the otocysts, which show a median outpocketing at the point of entrance of the endolymph duct. The ganglia of the nn. trigeminus, facialis, acus- ticus, and the superior ganglion of the glossopharyngeal nerve occur in order on each side. Sections of the anterior cardinal vein and its branches show on the left side. Ventral to the diencephalon are sections of the internal carotid arteries. TRANSVERSE SECTIONS OF A SIX MM. PIG EMBRYO I05 Passing along down the series into the pharynx region, observe the first, second, and third pharyngeal pouches. Their dorsal diverticula come into contact with the ectoderm of the branchial clefts and form the closing plates. Transverse Section through the Branchial Arches and the Eyes (Fig. 107).— The section passes lengthwise through the four branchial arches, the fourth sunken in the cervical sinus. Dorsad is the spinal cord with the first pair of cervical ganglia. The pharynx is cut across between the third and fourth branchial pouches. In its floor is a prominence, the anlage of the epiglottis. Ventral to the pharynx the ventral aorta gives off two pairs of vessels. The larger pair are the fourth aortic arches which curve dorsad around the pharynx to enter the descending aorte. The smaller third aortic arches enter the third branchial arches on each side. A few sections higher up in the series the ventral aorta bifurcates and the right Neural tube Myotome Notochord Ant. cardinal vein ~ Descending aorta Pharynx “Branchial arch 4 Pharyngeal pouch 3. Branchial arch 3 Aortic arch ros Branchial arch 2 Pharyngeal pouch 2 Lens of eye Optic vesicle Diencephalon Fic. 107.—Transverse section through the branchial arches and eyes of a 6 mm. pig embryo. X 26.5. X, aortic arch 4. and left trunks thus formed give off the first and second pair of aortic arches. Cranially in the angle between their common trunks lies the median thyreoid anlage. The anterior cardinal veins are located lateral and dorsal to the descending aorte. The end of the head is cut through the diencephalon and the optic vesicles. On the left side of the figure the lens vesicle may be seen still connected with the ectoderm. The optic vesicle now shows a thick inner, and a thin outer layer; these form the nervous and pigment layers of the retina respectively. Transverse Section through the Tracheal Groove, Bulbus Cordis and Olfactory Pits (Fig. 108).—The ventral portion of the figure shows a section through the tip of the head. The telencephalon is not prominent. The ectoderm is thickened and slightly invagi- nated ventro-laterad to form the anlages of the olfactory pits. These deepen in later stages and become the nasal cavities. In the dorsal portion of the section may be seen the cervical 106 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS Spinal cord Notochord Ant. cardinal vein Somato pleure Olfactory pil Fic. 108.—Transverse section through the bulbus cordis and olfactory pits of a 6 mm. pig embryo. X 26.5. Myotome L. common cardinal vein Descending aorla—f 4 pret Trachea Sinus venosus Valve of sinus venosus L. atrium R. atrium -Seplum I ' , LL. ventricle Atrio-ventricular foramen 2 FI nterventricular foramen Interventricular sc plum Pericardial cavity R. ventricle Somatopleure Fic. 109.—Transverse section through the four chambers of the heart of a6 mm. pig embryo. X 26.5. TRANSVERSE SECTIONS OF A SIX MM. PIG EMBRYO 107 portion of the spinal cord, the notochord just ventral to it, the descending aorta, and ventro- lateral to them the anterior cardinal veins. The nasopharynx now is small with a vertical groove inits floor. This is the tracheal groove and more caudad it will become the cavity of the trachea. The bulbus cordis lies in the large pericardial cavity. On either side the section cuts through the cephalic portions of the atria. These will become larger as we go caudad in the series. Transverse Section through the Heart (Fig. 109).—Lateral to the descending aorte are the common cardinal veins. The right common cardinal opens into the sinus venosus which in turn empties into the right atrium, its opening being guarded by the two valves of the sinus venosus. The entrance of the left common cardinal into the sinus venosus is some- what more caudad in the series. The ¢rachea has now separated from the esophagus and lies ventraltoit. Both trachea and esophagus are surrounded by a condensation of mesenchyme. ‘The myocardium of the ventricles has formed a spongy layer much thicker than that of the Spinal cord Upper limb bud Descending aorta Post. cardinal vein Pleuro-peritoneal cavity R. lung bud Esophagus Dorsal lobe of liver R. vitelline vein Lesser sac eptum transversum ei a A Septum transv L. vitelline vein Pericardial cavity L. ventricle Fic. 110.—Transverse section through the right lung bud and septum transversum of a 6 mm. pig embryo. X 26.5. atrial wall. An incomplete interventricular septum leaves the ventricles in communication dorsad. The septum primum is complete in this section, but higher up in the series there is an interatrial foramen (cf. Fig. 101). The foramen ovale is hardly formed. Transverse Section through the Lung Buds and Septum Transversum (Fig. 110).—The section passes through the bases of the upper limb buds. The tips of the ventricles lying in the pericardial cavity still show in this section. Dorsally the pericardial cavity has given place to the pleuro-peritoneal cavity. Projecting ventrad into this cavity are the meso- nephric (Wolffian) folds in which the posterior cardinal veins partly lie. Into the floor of the pleuro-peritoneal cavities bulge the dorsal lobes of the liver, embedded in mesenchyma. This mesenchyma is continuous with that of the somatopleure, and forms a complete trans- verse septum ventrally between the liver and heart. This is the septum transversum which takes part in forming the ligaments of the liver and is the anlage of a portion of the diaphragm. The two proximal trunks of the vitelline veins pass through the septum. Projecting laterally ~ 108 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS into the pleuro-peritoneal cavities are ridges of mesencyhma. covered by splanchnic mesoderm in which the lungs develop as lateral buds from the caudal end of the trachea. The right lung bud is shown in the figure. Between ‘the esophagus and the lung is a crescent-shaped cavity, the cranial end of the lesser peritoneal sac. Transverse Section through the Stomach (Fig. 111).—The section passes through the upper limb buds and just caudal to the point at which the descending aorte unite to form the median dorsal aorta. As the liver develops in early stages, it comes into relation with the plica vene cave along the dorsal body wall at the right side of the dorsal mesogastrium. The space between the liver and plica to the right, and the stomach and its omenta to the left, is a caudal continuation of the lesser peritoneal sac. The dorsal wall of the stomach is rotated to the left, its ventral wall to the right. The liver shows a pair of dorsal lobes and contains large blood spaces and networks of sinusoids lined with endothelium. Ventral to the liver, the tips of the ventricles are seen. : Spinal cord Spinal ganglion — Spinal nerve Notochord Dorsal aorta Post. cardinal vein Upper limb bud Peritoneal cavily Lesser sac - Stomach Common hepatic vein (R. vilelline) L. ventral lobe of liver R, ventral lobe liver R. ventricle L. ventricle Fic. 111.—Transverse section through the stomach of a 6 mm. pig embryo. X 26.5. Transverse Section through the Hepatic Diverticulum (Fig. 112).—The upper limb buds are prominent in this section. The mesonephric folds show the tubules and glom- eruli of the mesonephroi and the posterior cardinal veins are connected with the mesonephric sinusoids. From the dorsal attachment of the liver there is continued down into this section a ridge on the dorsal body wall just to the right (left in figure) of the mesentery. In this ridge lies a small vein which connects cranially with the liver sinusoids, caudally with the right subcardinal vein. As it later forms a portion of the inferior vena cava, the ridge in which it lies is termed the plica vene cave or caval mesentery. The right dorsal lobe of the liver contains a large blood space into which the portal vein opens. The duodenum is ventral to the position occupied by the stomach in the previous section. There is given off from it ventrad and to the right the /epatic diverticulum. In the sections higher up small ducts from the liver tra- becule may be traced into connection with it. In the left ventral lobe of the liver, a large blood space indicates the position of the eft umbilical vein on its way to the ductus venosus. Transverse Section through the Dorsal Pancreas (Fig. 113).—At this level the upper limb buds still show; the mesonephroi are larger and marked by their large glomeruli. TRANSVERSE SECTIONS OF A SIX MM. PIG EMBRYO 10g The right posterior cardinal vein is broken up into mesonephric sinusoids. The vein in the plica venz cave will, a few sections lower, connect with the right subcardinal vein. The an- lage of the dorsal pancreas is seen extending from the duodenum dorsad into the mesenchyme Spinal cord Notochord Post. cardinal vein Post. cardinal vein f Dorsal aorta i ng Es Upper limb bud Inf. vena cava Dorsal mesogastrium Portabaein Dorsal lobe liver R. umbilical vein L. vitelline vein Hepatic diverticulum L. umbilical vein Peritoneal cavily Fic. 112.—Transverse section through the hepatic diverticulum of a 6 mm. pig embryo. X 26.5. ofthe mesentery. It soon bifurcates into a dorsal and right lobe, of which the latter is slightly lobulated. Ventro-lateral to the duodenum the anlage of the ventral pancreas is seen cut across. It may be traced cephalad in the series to its origin from the hepatic diverticulum. Myotome: Dorsal aorta L. post. cardinal vein R. post. cardinal vein Mesonephros Glomerulus of mesone phros Eonar oan ee Mesenter Inf. vena cava é y Dorsal pancreas Portal vein L. vitelline vein R. umbilical vein Duodenum Distal end of hepatic diverticulum L. umbilical vein Ventral pancreas Fic. 113.—Transverse section through the dorsal pancreas of a6 mm. pig embryo. X 26.5 To the right of the ventral pancreas lies the portal vein (at this level a portion of the right vitelline). To the left of the dorsal pancreas is seen the remains of the left vitelline vein. The ventral lobes of the liver are just disappearing at this level. In the mesenchyme which IIo THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS connects the liver with the ventral body wall lie on each side the umbilical veins, the left being the larger. Between the veins is the extremity of the hepatic diverticulum. The body wall is continued ventrad to form a short umbilical cord. Transverse Section at the Level of Origin of the Vitelline Artery and Umbilical Arteries (Fig. 114).—As the posterior half of the embryo is curved in the form of a half circle, sections caudal to the liver, like this one, pass through the lower end of the body at the level of the posterior limb buds. Two sections of the embryo are thus seen in one, Spinal cord Spinal nerve Notochord R. post. cardinal vein Post. cardinal vein Dorsal aorta y \esonephros +1. subcardinal vein R. subcardinal vein £-L. vitelline vein Mesentery Cephalic limb of intestine ; L. umbilical vein R. umbilical vein Caudal limb of intestine R. umbilical vein Tail L. umbilical vein Lower limb bud Rectum Mesonephric duct Ce AMesone phric tubule Dorsal aorta AMesodermal segment Spinal cord Fic. 114.—Transverse section of a 6 mm. pig embryo at the level of the origin of the vitelline artery. The lower end of the section passes through the posterior limb buds. X 26.5. their ventral aspects facing each other and connected by the lateral body wall. In the dorsal part of the section the mesonephroi are prominent with large posterior cardinal veins lying dor- salto them. The trunk of the vifelline artery takes origin ventrally from the aorta. It may be traced into the mesentery, and through it into the wall of the yolk sac. On either side of the vitelline artery are the subcardinal veins, the right being the larger. In the mesentery may be seen two sections of the intestinal loop (the small intestine being cut lengthwise, the large intestine transversely), and also sections of the vitelline artery and veins. In the lateral TRANSVERSE SECTIONS OF A SIX MM. PIG EMBRYO III body walls ventral to the mesonephros occur the umbilical veins. The left vein is large and cut lengthwise. The right vein is cut obliquely twice. In the ventral portion of the section, the lower limb buds are prominent laterally. A large pair of arteries, the common iliacs, are given off from the aorta and may be traced into connection with the umbilical arteries. The large intestine supported by a short mesentery lies in the coelom near the midline. On each side are the mesonephric folds, here small and each showing a section of the mesonephric duct and a single vesicular anlage of the mesonephric tubules. The mesonephric ducts are sectioned as they curve around from their position in the dorsal portion of the section. Section through the Primitive Segments and Spinal Cord (Fig. 115).—This sec- tion is near the end of the series and as the body is here curved it is really a frontal section. At the left side of the spinal cord the oval cellular masses are the spinal ganglia cut across. The ectoderm, arching over the segments, indicates their position. Each segment shows an outer dense layer, the cutis plate, lying just beneath the ectoderm. This plate curves lateral to the spindle-shaped muscle plate which gives rise to the voluntary muscle. Next comes a diffuse mass of mesen- chyma, the sclerotome, which eventually, with its fellow of the Spinal ganglionstpits Intersegmental X: artery { = : dee PICO oa q Muscle plateyg R. umbilical vein : NA ( J L. umbilical artery R. umbilical artery Tail . t ki es Cutis plate L. umbilical vein Sclerolome Allantois and cloaca L. umbilical artery Ectoderm i Mesonephric duct Spinal cord Notochord Fic. 115.—Transverse sec- Fic. 116.—Transverse section through the umbilical vessels, allan- tion through the primitive seg- tois and cloaca of a6mm. pigembryo. x 45. ments and spinal cord of a 6 mm. pigembryo. X 45. opposite side, surrounds the spinal cord’and forms the anlage of a vertebra. A pair of spinal nerves and spinal ganglia are developed opposite each somite, and pairs of small vessels are seen between the segments. These are dorsal intersegmental arteries. Section through the Umbilical Vessels, Allantois and Cloaca (Fig. 116).—Hav- ing now studied sections at various levels to near the end of the series we shall next examine sections through the caudal region and. study the anlages of the urogenital organs. Owing to the curvature of the embryo, it is necessary to go cephalad in our series. The first section passes through the bases of the limb buds at the level where the allantoic stalk, curving in- ward from the umbilical cord, opens into the cloaca. At either side of the allantoic stalk may be seen oblique sections of the umbilical arteries and lateral to these the large left and small right umbilical vein. The mesonephric ducts occupy the mesonephric ridges which project into small caudal prolongations of the celom. Midway between the ducts lies the hind-gut, dorsal to the cloaca. The tip of the tail is seen in section at the left of the figure. 112 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS Section through the Anlages of the Metanephroi, Cloaca and Hind-gut (Fig. 117).—The metanephroi are seen as dorsal evaginations from the mesonephric (Wolffian) ducts just before their entrance into the cloaca. Each consists of an epithelial layer surrounded by a condensation of mesenchyme. Traced a few sections cephalad the mesonephric ducts open Gag £-Veniral body wall @Al 4 — L. umbilical artery -L. umbilical vein Allantoic stalk R. umbilical vein R. umbilical artery Mesonephric duct f : Metanephric anlage \ + Spinal cord Fic. 117.—Transverse section through the anlages of the metanephroi of a 6 mm. pig embryo. X 45. into the lateral diverticula of the cloaca, which, irregular in outline because it is sectioned obliquely, lies ventral to them and receives dorsad the hind-gut. Caudal to the cloaca in this embryo the tail bends abruptly cephalad and to the right. The blind prolongation of the hind-gut may be traced out into this portion of the tail until it ends in a sac-like dilatation. B. THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS The study of embryos at this stage is important as they possess the anlages of most of the organs. The anatomy of a 12 mm. pig embryo has been carefully studied and described by Lewis (Amer. Jour. Anat., vol. 2, 1903). External Form (Fig. 118) —The head is now relatively large on account of the increased size of the brain. The third branchial arch is still visible in the embryo, but the fourth arch has sunken in the cervical sinus; usually both have disappeared at a slightly later stage. The olfactory pits form elongated grooves on the under surface of the head and the Jens of the eye lies beneath the ectoderm surrounded by the optic cup. The maxillary and mandibular processes of the first branchial arch are larger and the former shows signs of fusing with the median nasal process to form the upper jaw. Small tubercles, the anlages of the external ear, have developed about the first branchial cleft which itself becomes the external auditory meatus. At the cervical bend the head is flexed at right angles with the body, bringing the ventral surface of the head close to that of the trunk, and it is probably owing to this flexure that the third and fourth branchial arches buckle inward to form the cervical sinus. Dorsad, the trunk forms a long curve more marked opposite THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS 113 the posterior extremities. The reduction in the trunk flexures is due to the in- creased size of the heart, liver, and mesonephroi. These organs may be seen M yelencephalon Branchial cleft 1 Hyoid Le Cervical flexure oS ee flexure Branchial arch 3 ~f: Cervical sinus , Maxillary process Mandibular process Upper limb bud Olfactory pit Milk line A Ve" iD Mesodermal segment ay va So e Lower limb bud Fic. 118.—Exterior of a 10 mm. pig,embryo viewed from the right side. X 7. through the translucent body wall and the position of the septum transversum may be noted between the heart and the diaphragm, as in Fig. 120. The limb Cervical flexure External ear Mandibular process Upper limb bud Mesodermal segment Yolk stalk _ Lower limb bud Yolk sac Fic. 119.—Exterior of a human embryo of 12 mm., viewed from the right side, showing attachment : of amnion (cut away) and yolk stalk and sac. X 4. buds are larger and the umbilical cord is prominent ventrad. Dorsally the meso- dermal segments may be seen, and extending in a curve between the bases of the 8 , II4 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS limb buds is the milk line, a thickened ridge of ectoderm which forms the anlages of the mammary glands. The tail is long and tapering. Between its base and the umbilical cord is the genital eminence (Fig. 120). Human embryos of this stage or slightly older vary considerably in size (Fig. 119). They differ from pig embryos in the greater size of the head, the Metencephalon N. trochlearis Mesencephalon Gang. nm. 5 . N. oculomotorius Gang. nn. 7 and 8 N. facialis Gang. superior n. 9 \ Gang. jugulare n. 10 | A Gang. pelrosal n. 9 Dicence phalon Gang. Froriep Ophthalmic r. n. 5 Gang. nodos. 1. 10 : . oplicus N. accessorius Maxillary ron. 5 N. hypoglossus Telencephalon Atrium Lung Mandibular r. n. 5 Gang. cerv. 8 Septum transversum Chorda tymp. n. 7 Livers i “entricle Mesonephros Gang. thorac. 10 Umbilical cord Genital eminence Fic. 120.—Lateral dissection of a 10 mm. pig embryo, showing the viscera and nervous system from the right side. The eye has been removed and the otic vesicle is represented by a broken line. The ventral roots of the spinal nerves are not indicated. % 10.5. m., Nerve; r., ramus. shorter tail, the much smaller mesonephric region, the longer umbilical cord, and the less prominent segments. The yolk sac is pear-shaped and the yolk stalk is long and slender. Central Nervous System and Viscera.—Dissections show well the form and relations of the organs (Figs. 120, 121 and 122). Directions for preparing dis- sections are given in Chapter VI. THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS II5 Brain.—Five distinct regions may be distinguished (Figs. 120 and 122): (1) The telencephalon with its rounded lateral outgrowths, the cerebral hemispheres. Their cavities, the Jateral ventricles, communicate by the interventricular foramina with the third ventricle. (2) The diencephalon shows a laterally flattened cavity, the third ventricle. Ventro-laterally from the diencephalon pass off the optic stalks and an evagination of the mid-ventral wall is the anlage of the posterior hypophyseal lobe. (3) The mesencephalon is undivided, but its cavity becomes the cerebral aqueduct leading caudally into the fourth ventricle. (4) The metencephalon is separated from the mesencephalon-by a constriction, the isthmus. Dorso-later- Accessory gang. I Accessory gang. 2 Acc. gang. 3 Myelencephalon Acc. gang. 4 Gang. sup. Gang. jugulare Gang. Froriep —> N.ar Cerv. gang. I Gang. petrosum N.9g Cerv. gang. 2 N.1r Gang. nodosum N. 12 Fic. 121.—Duissection of the head of a 15 mm. pig embryo from the right side to show the accessory vagus ganglia with peripheral roots passing to the hypoglossal nerve. X 25. ally it becomes the cerebellum, ventrally the pons. (5) The elongated myelen- cephalon is roofed over by a thin non-nervous ependymal layer. Its ventro-lateral wall is thickened and still gives internal indication of the neuromeres. The cavity of the metencephalon and myelencephalon is the fourth ventricle. Cerebral Nerves.—Of the twelve cerebral nerves all but the first (olfactory) and sixth (abducens) are represented in Fig. 120. For a detailed description of these nerves see Chapter XIII. (2) The optic nerve is represented by the optic stalk cut through in Fig. 120. (3) The oculomotor, a motor nerve to four of the eye muscles, takes origin from the ventro-lateral wall of the mesencephalon. (4) 116 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS The trochlear nerve fibers, motor, to the superior oblique muscle of the eye, arise from the ventral wall of the mesencephalon, turn dorsad and cross at the isthmus, thys emerging on the opposite side. From the myelencephalon arise in order (5) the trigeminal nerve, mixed, with its semilunar ganglion and three branches, the ophthalmic, maxillary, and mandibular; (6) the . abducens, motor, from the ventral wall to the external rectus muscle of the eye; (7) the 2. facialis, mixed, with its geniculate ganglion and its chorda tympant, facial, and superficial petrosal branches in the order named; (8) the 2. acusticus, sensory, arising cranial to the otocyst, with its acoustic ganglion and sensory fibers to the internal ear; (9) caudal to the otocyst the n. glossopharyngeus, mixed, with its superior and petrosal ganglia; (10) the vagus, sensory, with its jugular and nodose ganglia; (11) accom- panying the vagus the motor fibers of the spinal accessory which take origin between the jugular and sixth cervical ganglia from the lateral wall of the spinal cord and myelencephalon; the internal branch of the n. accessorius accompanies the vagus; the external branch leaves it between the jugular and nodose ganglia and supplies the sternocleidomastoid and trapezius muscles; (12) the ~. hypoglos- sus, motor, arising by five or six fascicles from the ventral wall of the myelen- cephalon; its trunk passes lateral to the nodose ganglion and supplies the muscles of the tongue. A nodular chain of ganglion cells extends caudad from the jugular ganglion of the vagus. These have been interpreted as accessory vagus ganglia. They may, however, be continuous with Froriep’s ganglion which sends sensory fibers to the n. hypoglossus. In pig embryos of 15 to 16 mm. this chain is frequently divided into four or five ganglionic masses, of which occasionally two or three (including Froriep’s ganglion) may send fibers to the root fascicles of the hypoglossal nerve. Such a condition is shown in Fig. 121. Spinal Nerves.—These have each their spinal ganglion, from which the dorsal root fibers are developed (Figs. 120 and 136). The motor fibers take origin from the ventral cells of the neural tube and form the ventral roots which join the dorsal roots in the nerve trunk. In Fig. 120 the heart with its right atriwm and ventricle, the dorsal and ven- tral lobes of the liver, and the large mesonephros are prominent. Dorsal and somewhat caudal to the atrium is the anlage of the right lung. The sepium transversum extends between the heart and the liver. Pharynx and its Derivatives.—Dorsally the anterior lobe of the hypophysis is long and forks at its end (Figs. 122 and 123). In the floor of the pharynx are the anlages of the tongue and epiglottis (Fig. 156 A). From each mandibular arch arises an elongated thickening which extends caudal to the second arch. Be- THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS 117 ‘tween, and fused to these thickenings, is the triangular tuberculum impar. The opening of the thyreoglossal duct between the tuberculum impar and the second arch is early obliterated. A median ridge, or copula, between the second arches connects the tuberculum impar with the epiglottis, which seems to develop from the bases of the third and fourth branchial arches. On either side of the slit-like Metencephalon., Mesencephalon Tela choroidea Neuromeres of myelence phalon \ a Diencephalon Notochord ; Tongue xe LG KG fi Post. lobe hypophysis Spinal cord \_f/ Pf Oplic recess Esophagus ™ j Trachea ff lf Telencephalon Ant. lobe hypophysis Atrium . Bulbus cordis mse. F Lung Se iy f Ventricle 4 i @ Yolk sac Stomach} x ee ye eee) > Seplum transversum Dorsal Pancreas Y ; Yolk stalk s\ Liver 5 a 1 a £9 Hepatic diverticulum YT” SL << Y Cacum ee ae Duodenum aaa ‘Small intestine L. genital fold a ‘Allantois . , J C Nr . : L. mesonephros’ “ aS — Urogenital sinus Dorsal aorta x baemecer oe \ Ureter Colon ali Mesonephric duct Umbilical artery (cut away) Metanephros Rectum Fic. 122.—Median sagittal dissection of a 10 mm. pig embryo, showing the brain, spinal cord and viscera from the right side. X 10.5. glottis are the arytenoid folds of the larynx. (For the development of the tongue, see p. 149.) The pharyngeal pouches are now larger than in the 6 mm. pig (Fig. 123). The first pouch persists as the auditory tube and middle ear cavity, the closing plate between it and the first branchial cleft forming the tympanic membrane. The second pouch later largely disappears; about it, develops the 118 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS palatine tonsil. ‘The third pouch is tubular, directed at right angles to the phar- ynx, and meets the ectoderm to form a “‘closing plate.” Median to the plate, the ventral diverticulum of the third pouch is the anlage of the thymus gland. Its dorsal diverticulum forms an epithelial body, or parathyreoid. The fourth pouch is smaller and its dorsal diverticulum gives rise to a second parathyreoid Gang. nn.7 and 8 Gang. n. 5 Otocyst Pharyngeal pouch 2 Gang. jugulare n. 10 Post. lobe hypophysis SHEE \ Ant. lobe hy pophysis \ Caudal root n. hy poglossus Pharyngeal pouch r Maxillary process Thyreoid gland Aorlic arch 4 Gang. cerv. I Pharyngeal pouch 4 Pulmonary artery ey cn Aorta NI Aortic arch 5 AN ni a7 SEU SS I R. descending aorta AWAY oS JUS Eso phag _ Septum transversum Trachea sss ANG Ss Vertebral artery Subclavian artery Hepatic diverticulum Cloaca ~ Allantois Rectum

10. body. Its ventral diverticulum is a rudimentary thymus anlage. A tubular outgrowth, caudal to the fourth pouch, is regarded as a fifth pharyngeal pouch in human embryos and forms the ultimobranchial body on each side (see p. 164). The thyreoid gland, composed of branched cellular cords, is located in the mid- line between the second and third branchial arches (Fig. 123). THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS I1IQ Trachea and Lungs.—Caudal to the fourth pharyngeal pouches the esoph- agus and trachea separate and form entodermal tubes (Figs. 122 and 123). Cephalad of the point where the trachea bifurcates to form the primary bronchi there appears on its right side the tracheal bud of the upper lobe of the right lung (Fig. 124). This bronchial bud is developed only on the right side and appears in embryos of 8 to9 mm. Two secondary bronchial buds arise from the primary bronchus of each lung, and form the anlages of the symmetrical lobes of each lung. Olfactory pit Lateral nasal process ——~___ Lacrymal groove ~~ SS ive ~— Median nasal process Maxillary process — Branchial arch 2 _____ Branchial arch 3 — Branchial arch 4 Mandibular process Cervical sinus Trachea Tracheal lung bud , oy) L 7— Esophagus Upper limb bud i Ua Septum transversum Mesonephric duct Hepatic diverticulum Ventral pancreas Yolk sac § iy !) —~ Mesonephros — Cephalic limb of intestine ——~ Caudal limb of intestine Allantois = R. umbilical artery — ~~ Rectum a oe SG yf - ~~ Metanephros Lower limb bud ~ ue Mesonephric duct Spinal cord Rectum Fic. 124.—Ventral dissection of a 9 mm. pig embryo. The head is bent dorsad. X 9. Esophagus and Stomach.—The esophagus extends as a narrow tube caudal to the lungs, where it dilates into the stomach. The stomach is wide from its greater to its lesser curvature and shows a cardiac diverticulum (Lewis). The pyloric end of the stomach has rotated more to the right, where it opens into the duodenum, from which division of the intestine the liver and pancreas develop. The liver, with its four lobes, fills in the space between the heart, stomach, and duodenum (Fig. 122). Extending from the right side of the duodenum along the dorsal and caudal surface of the liver is the hepatic diverticulum. It lies to 120 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS the right of the midline and its extremity is saccular. This saccular portion becomes the gall bladder. Several ducts connect the diverticulum with the liver cords. One of these persists as the hepatic duct which joins the cystic duct of the gall bladder. The portion of the diverticulum proximal to this union becomes the common bile duct, or ductus choledochus. The ventral pancreas arises from the common bile duct near its point of origin (Fig. 123). It is directed dorsad and caudad to the right of the duodenum. The dorsal pancreas arises more caudally from the dorsal wall of the duodenum and its larger, lobulated body grows dor- sally and cranially (Figs. 123, 127 and 140). Between the pancreatic anlages courses the portal vein. In the pig, the duct of the dorsal pancreas persists as the functional duct. Intestine.—Caudal to the duodenum, the intestinal loop extends well into the umbilical cord (Figs. 122 and 123). At the bend of the intestinal loop is the slender yolk stalk. The cephalic limb of the intestine lies to the right, owing to the rotation of the loop. The small intestine extends as far as a slight enlarge- ment of the caudal limb of the loop, the anlage of the cecum, or blind gut. This anlage marks the beginning of the large intestine (colon and rectum). The intestinal loop is supported by the mesentery which is cut away in Fig. 122. The cloaca is now nearly separated into the rectum and urogenital sints. The cavity of the rectum is almost occluded by epithelial cells (Lewis). Urogenital System.—The mesonephros is much larger and more highly dif- ferentiated than in the 6 mm. embryo (Figs. 120 and 124). Along the middle of its ventro-median surface the genital fold is now more prominent (Fig. 122). In a ventral dissection (Fig. 124) the course of the mesonephric ducts may be traced. They open into the urogenital sinus, which also receives the allantoic stalk (Fig. 122). The metanephros, or permanent kidney anlage, lies just mesial to the um- bilical arteries where they leave the aorta (Fig. 123). Its epithelial portion, derived from the mesonephric duct, is differentiated into a proximal, slender duct, the ureter, and into a distal, dilated pelvis. From this grow out later the calyces and collecting tubules of the kidney. Surrounding the pelvis is a layer of con- densed mesenchyma, or nephrogenic tissue, which is the anlage of the remainder of the kidney. Blood Vascular System.—The Heart.—In Fig. 125 the cardiac chambers of the right side are opened. The septum primum between the atria is perforated dorsad and cephalad by the foramen ovale. The inferior vena cava is seen opening oS into the sinus venosus, which in turn communicates with the right atrium through THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS 121 a sagittal slit guarded by the right and left valves of the sinus venosus. The right valve is the higher and its dorsal half is cut away. The valves were united cephalad as the septum spurium. Between the left valve and the septum primum the sickle-like fold of the septum secundum is forming; the fusion of these three components gives rise later to the adult atrial septum. The aortic bulb is divided distally into the aorta and the pulmonary artery, the latter connecting with the fifth pair of aortic arches. Proximally the bulb is undivided. The inlerven- tricular septum is complete except for the interventricular foramen which leads from the left ventricle into the aortic side of the bulb. Of the bulbar swellings which divide the bulb into aorta and pulmonary trunk, the Jeft joins the inter- ventricular septum, while the right extends to the endocardial cushion. These folds eventually fuse and the partition of the ventricular portion of the heart is Sept. IT R. atrium Sept. I Foramen ovale Left valve of sinus venosus Right valve of sinus venosus — Aorta Inferior vena cava “Pulmonary artery s—Interventricular foramen R. ventricle Fic. 125.—Heart of 12 mm. embryo dissected from the right side. completed. The endocardium at the atrio-ventricular foramina is already under- mined to form the anlages of the tricuspid and bicuspid valves. From the caudal wall of the left atrium there is given off a single pulmonary vein. The Arteries —As seen in Fig. 123, the first two aortic arches have dis- appeared. Cranial to the third arch, the ventral aorte become the external carotids. The third aortic arches and the cephalic portions of the descending aorte constitute the internal carotid arteries. The ventral aorte between the third and fourth aortic arches persist as the common carotid arteries. The de- scending aorte in the same region are slender and eventually atrophy. The fourth aortic arch is largest and on the left side will form the aortic arch of the adult. From the right fourth arch caudad, the right descending aorta is smaller than the left. Opposite the eighth segment, the two aorte unite and continue 122 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS caudally as the median dorsal aorta. The fifth (sixth ?) aortic arches (cf. p. 99) are connected with the pulmonary trunk, and from them arise small pulmonary arteries to the lungs. Dorsal intersegmental arteries arise, six pairs from the de- scending aorte, others from the dorsal aorta. From the seventh pair, which arise just where the descending aorte fuse, the subclavian arteries pass off to the upper limb buds and the vertebral arteries to the head. The latter are formed Fic. 126 A.—Reconstruction of a 12 mm. pig embryo to show the veins and heart from the left side. For names of parts see Fig. 126 B on opposite page (F. T. Lewis). X 9. by a longitudinal anastomosis between the first seven pairs of intersegmental arteries on each side, after which the stems of the first six pairs atrophy. Ventro-lateral arteries from the dorsal aorta supply the mesonephros and genital ridge (Fig. 123). Ventral arteries form the celiac artery to the stomach region, the vitelline or superior mesenteric artery to the small intestine, and the inferior mesenteric artery to the large intestine. THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS 123 The umbilical arteries now arise laterally from secondary trunks which persist as the common iliac arteries. The Veins.—The cardinal veins have been reconstructed by Lewis in a 12 mm. pig (Fig. 126). The veins of the head drain into the anterior cardinal vein, WA eer Z \ y L WAL . “y Ul eS Oo Mog i q: kh Fic. 126 B.—Reconstruction of a 12 mm. pig embryo to show the veins from the left side (Lewis). X 9. A., Umbilical artery; Ao., aorta; Au., right auricle (atrium); card.’, card.”, superior and in- ferior sections‘of posterior cardinal vein; d, left common cardinal vein; D.C., right common cardinal vein; D.V., ductus venosus; Jug.’, Jug.”, jugular or ant. cardinal vein; L., liver; L.o., anlage of lateral sinus; mx, transverse vein; P., pulmonary artery; Sc., subcardinal vein; Sc/., subclavian vein; sls., anlage of sup. longitudinal sinus; Um.d., right umbilical vein; Ven., right ventricle, V.H.C., common hepatic vein; V.op., ophthalmic vein; V.P., portal vein; X, anastomosis between the right and left subcardinal veins. which becomes the internal jugular vein of the adult. After receiving the ex- ternal jugular veins and the subclavian veins from the upper limb buds the anterior cardinals open into the common cardinal veins (duct of Cuvier). The posterior cardinal veins arise in the caudal region, course dorsal to the mesonephroi, and drain the mesonephric sinusoids. The subcardinal veins 124 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS anastomose just caudal to the origin of the superior mesenteric artery and the posterior cardinals are interrupted at this level. The proximal portions of the posterior cardinals open into the common cardinal veins as in the 6 mm. embryo. Of the two subcardinal veins, the right has become very large through its con- nection with the right posterior cardinal vein and the common hepatic vein, and now forms the middle portion of the inferior vena cava. For the development of this vein, see Chapter IX. Notochord Spinal cord Ant. cardinal vein Esophagus Pharynx R. ant. cardinal vein Trachea Pericardial cavily Uber lamb Common car- dinal vein Sinus venosus Inf. vena cava-$ Duclus venosus Liver Portal vein —* a J ee Pyloric stomach Ventral pancreas Ilepalic diverticulum Caecum Dorsal pancreas L. vitelline vein Small intestine Duodenum L. umbilical vein Sup. mesenteric vein eas i Allantois R. umbilical vein R. umbilical artery Fic. 127.—Reconstruction of a 10 mm. pig embryo to show the umbilical and vitelline veins from the ventral side. x indicates sinusoidal connection between left umbilical vein and portal vein. X 15. In the small orientation figure (cf. Fig. 123) the various planes are indicated by broken lines— The umbilical veins (Figs. 126 and 127) anastomose in the umbilical cord, separate on entering the embryo, and course cephalad in the ventro-lateral body wall of each side to the ventral lobe of the liver. The Jeff vein is much the larger, and, after entering the liver, its course is to the right and dorsad. After connecting with the portal vein, it continues as the ductus venosus and joins the proximal end of the inferior vena cava. The smaller right umbilical vein after entering the liver breaks up into sinusoids. It soon atrophies, while the left vein persists until after birth. The Vitelline Veins.—Of these, a distal portion of the left and a proximal TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO |. 125 portion of the right are persistent. The left vitelline vein, fused with the right, courses from the yolk sac cephalad of the intestinal loop. Near a dorsal anas- tomosis between the right and left vitelline veins, just caudal to the duct of the dorsal pancreas, the left receives the superior mesenteric vein, a new vessel arising in the mesentery of the intestinalloop. Cranial to its junction with the superior mesenteric vein, the left vitelline, with the dorsal anastomosis and the proximal portion of the right vitelline vein, form the portal vein, which gives off branches to the hepatic sinusoids and connects with the left umbilical vein. For the develop- ment of the portal vein, see Chapter IX. TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO Figures are shown of sections passing through the more important regions and should be used for the identification of the organs. The level and plane of each section is indicated by guide lines on Fig. 128. The student should compare Metencephalon Myelence phalon Aesencephalon Gang. sup. n. 9 Gang. and n. access. Diencephalon 129 Lelence phalon 130 I3L , Olfactory pit Pulmonary artery os 134 136 137 138 139 140 T4I 142 T43 “) or ee ay ‘by Lip 2 Z : fi) baad Ged oad Fic. 128.—Reconstruction of a 10 mm. pig embryo, showing the chief organs of the left side. The numbered lines indicate the levels of transverse sections shown in the corresponding figures (129-143). For the names of the various structures not lettered see Fig. 123. X 8. this with Figs. 118 and 123, and orient each section with reference to the embryo asa whole. To avoid repetition most of the levels illustrated in the transverse sections of the 6 mm. pig are not represented in the 10 mm. series. For this reason 126 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS the former series will be found very instructive in supplementing the following descriptions. Transverse Section through the Eyes and Otocysts (Fig. 129).—The brain is sectioned twice, lengthwise through the myelencephalon, transversely through the fore-brain. The brain wall shows differentiation into three layers: (1) an inner ependymal layer densely cellular; (2) a middle manile layer of nerve cells and fibers; (3) an outer marginal layer chiefly fibrous. These same three layers are developed in the spinal cord. A thin vascular layer differentiated from the mesenchyma surrounds the brain wall and is the anlage of the pia mater. The myelencephalon shows three neuromeres in this section. The telencephalon is Fourth ventricle Wall of myelencephalon N. accessorius Gang. jugulure n. 10 Sle N. glossopharyngeus Olocyst Gang. acust. n. 8 Gang. geniculat. n. 7 N. abducens } Mandibular ramus n. 5 Basilar artery . S nt = Maxillary ramus n. 5 LOUMSSGGDET IOS US Int. carotid artery Ant. lobe hypo physis O plic vesicle Lens vesicle Third ventricle of diencephalon ROREINEN: inlerveniriculare Lat. ventricle of telencephalon Fic. 129.—Transverse section passing through the eyes and otocysts of a10 mm. pig embryo. X 22.5. represented by the paired cerebral hemispheres, their cavities, the Jateral ventricles, connecting through the interventricular foramina with the third ventricle of the diencephalon. Close to the ventral wall of the diencephalon is a section of the anterior lobe of the hypophysis (Rathke’s pocket) near which are the ‘nternal carotid and basilar arteries. Lateral to the diencephalon “is the optic cup and lens vesicle of the eye, which are sectioned caudal to the optic stalk. The outer layer of the optic cup forms the thin pigment layer; the inner thicker layer, is the mervous layer of the retina. The lens is now a closed vesicle distinct from the overlying corneal ectoderm. The large vascular spaces are the cavernous sinuses, which drain by way of the vv. capitis laterales into the internal jugular veins. Transverse sections may be seen of the maxillary TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO 127 and mandibular branches of the n. trigeminus; the n. abducens is sectioned longitudinally. The small nn. oculomotorius and trochlearis should be identified in sections more cephalad in the series. Ventral to the otocyst are seen the geniculate and acoustic ganglia of the nn. facialis and acusticus. The wall of the ofocyst forms a sharply defined epithelial layer. More cephalad in the series the endolymph duct lies median to the otocyst and connects with it. Dorsal to the otocyst the x. glossopharyngeus and the jugular ganglion of the vagus are cut transversely while the trunk of the x. accessorius is cut lengthwise. Section through the First and Second Pharyngeal Pouches (Fig. 130).—The end of the head, with sections of the felencephalon and of the ends of the olfactory pits, is now N. accessorius 5 5 Neural cavity Gang. Froriep Myelence phalon Roots of n. hypoglossus Basilar artery Int. jugular vein Notochord Nn. vagus et accessorius Descending aorta Gang. petrosal n. 9 Me gaciales Pharyngeal pouch 2 i Branchial arch 2 Ti Pharyngeal pouch 1 ss L Mandible Maxillary process Olfactory pit Telencephalon Fic. 130.—Transverse section passing through the first and second pharyngeal pouches of a 10 mm. pig embryo. X 22.5. distinct from the rest of the section. The pharynx shows portions of the first and second pharyngeal pouches. Opposite the first pouch externally is the first branchial cleft. A section of the tuberculum impar of the tongue shows near the midline in the pharyngeal cavity. The neural tube is sectioned dorsally at the level of Froriep’s ganglion. Between the neural tube and the pharynx may be seen on each side the several root fascicles of the 2. hypoglossus, the fibers of the nn. vagus and accessorius, and the petrosal ganglion of the n. glossopharyngeus. Mesial to the ganglia are the descending aorte and lateral to the vagus is the internal jugular vein. 128 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS Section through the Third Pharyngeal Pouches (Fig. 131).—The tip of the head is now small and shows on either side the deep olfactory pits lined with thickened olfactory epi- thelium. The first, second, and third branchial arches show on either side of the section, the third being slightly sunken in the cervical sinus. The dorsal diverticula of the third pharyn- geal pouches extend toward the ectoderm of the third branchial cleft. The ventral diverticula or thymic anlages may be traced caudad in the series. The floor of the pharynx is sectioned through the epigloitis. Ventral to the pharynx are sections of the third aortic arches and the solid cords of the thyreoid gland. Dorsally the section passes through the spinal cord and first pair of cervical ganglia. Between the cord and pharynx, named in order, are the internal jugular veins, the hypoglossal nerve, and the nodose ganglion of the vagus. Lateral to the Spinal ganglion Notochord Int. jugular vein N. hypoglossus Ext. branch n. accessorius Gang. nodos. n. 10 Epigloltis Branchial arch 3 Branchial arch 24 Thyreoid anlage Mandible Olfactory pit Olfactory epithelium Fic. 131.—Transverse section through the third pharyngeal pouches of a 10 mm. pig embryo. X 22.5. ganglion is the external branch of the n. accessorius, and mesial to the ganglia are.the small descending aorta. Section through the Fourth Pharyngeal Pouches (Fig. 132).—This region is marked by the disappearance of the head and the appearance of the heart in the pericardial cavity. The tips of the atria are sectioned as they project on either side of the bulbus cordis. The bulbus is divided into the aorta and pulmonary artery, the latter connected with the right ventricle, which has spongy muscular walls. The pharynx is crescentic and continued laterally as the small fourth pharyngeal pouches. Into the mid-ventral wall of the pharynx opens the vertical slit of the trachea. A section of the vagus complex is located between the descending aorta and the internal jugular vein. At this level the jugular vein receives the linguo-facial TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO 129 Spinal cord Spinal ganglion R. descending aorta L, descending aorla Int. jugular vein Pharynx aan ti Pharyngeal pouch 4 Tracheal groove R. atrium 4 Aorta Pulmonary artery R. ventricle Fic. 132.—Transverse section through the fourth pharyngeal pouches of a 10 mm. pigembryo. X 22.5. Spinal ganglion Spinal cord Notochord R. descending aorta Esophagus Trachea L. atrium Aorta Pulmonary artery R. atrium Cavity of bulbus ‘ R. ventricle Fic. 133.—Transverse section through the fifth pair of aortic arches and bulbus cordis of a 10 mm. pig embryo. X 22.5. 130 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS vein. The left descending aorta is larger than the right. The ventral aorta may be traced cranially in the series to the fourth aortic arches. The pulmonary artery, if followed caudad, connects with the fifth aortic arches as in Fig. 133. Section through the Fifth Aortic Arches (Fig. 133).—The fifth aortic arch is com- plete on the left side. From these pulmonary arches small pulmonary arteries may be traced caudad in the series to the lung anlages. The esophagus, now separate from the trachea, forms a curved horizontal slit. All four chambers of the heart are represented, but the aorta and pulmonary artery are incompletely separated by the right and left bulbar swellings or folds. Section through the Sinus Venosus and the Heart (Fig. 134).—The section is marked by the symmetrically placed atria and ventricles of the heart and by the presence of Spinal cord Spinal ganglios Notochord Upper limb bud R. descending aorla Esophagus g aorta’ dg L. common cardinal vein Sinus venosus : Trac hea R. valve of sinus venosus L. atrium Pericardial cavity R. ventricles Uy Te She & et Body wall Interventricular se plum—-* Fic. 134.—Transverse section through the sinus venosus of the heart ina 10 mm. pig embryo. X 22.5. the upper limb buds. Dorsal to the atria are the common cardinal veins, the right vein forming part of the sinus venosus. The sinus venosus drains into the right atrium through a slit-like opening in the dorsal and caudal atrial wall. The opening is guarded by the right and left valves of the sinus venosus, which project into the atrium. The septum primum completely divides the right and left atria at this level, which is caudal to the foramen ovale and the atrio-ventricular openings. The septum joins the fused endocardial cushions. Note that the esophagus and trachea are now tubular and that the left descending aorta is much larger than the right. Around the epithelium of both trachea and esophagus are condensations of mesenchyma, from which their outer layers are differentiated. Section through the Foramen Ovale of the Heart (Fig. 135).—The level of this section is cranial to that of the previous figure and shows the septum primum interrupted dor- sally to form the foramen ovale. Each atrium communicates with the ventricle of the same TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO 131 side through the atrio-ventricular foramen. Between these openings is the endocardial cushion, which in part forms the anlages of the tricuspid and bicuspid valves. The atria are marked off externally from the ventricles by the coronary sulcus. Between the two venticles is the inter- ventricular septum. The ventricular walls are thick and spongy, forming a network of muscu- lar cords or trabecule surrounded by blood spaces or sinusoids. The trabeculae are composed of muscle cells, which later become striated and constitute the myocardium. They are sur- rounded by an endothelial layer, the endocardium. The mammalian heart receives all its nourishment from the blood circulating in the sinusoids until later, when the coronary vessels of the heart wall are developed. The heart is surrounded by a layer of mesothelium, the epicardium, which is continuous with the pericardial mesothelium lining the body wall. Section through the Liver and Upper Limb Buds (Fig. 136).—The section is marked by the presence of the upper limb buds, the liver, and the bifurcation of the trachea to form the primary bronchi of the lungs. The limb buds are composed of dense undifferentiated mesenchyme surrounded by ectoderm which is thickened at their tips. The seventh pair of cervical ganglia and nerves are cut lengthwise showing the spindle-shaped ganglia with the dorsal root fibers taking origin from their cells. The ventral root fibers arise from the ventral Foramen ovale : : L. atrium R. atrium . . Endocardial cushion R. atrio-ventricular foramen L. atrio-ventricular foramen R. ventricle-8 E L. ventricle Interventricular septum Fic. 135.—Transverse section through the foramen ovale of the heart ina 10 mm. pig embryo. X 22.5. cells of the mantle layer and join the dorsal root to form the nerve trunk. On the right side a short dorsal ramus supplies the anlage of the dorsal muscle mass. The much larger ventral ramus unites with those of other nerves to form the brachial plexus. The descending aorte have now fused and the seventh pair of dorsal intersegmental arter- ies arise from the dorsal aorta. From these intersegmental arteries the subclavian arteries are given off two sections caudad in the series. Lateral to the aorta are the posterior cardinal veins. The esophagus, ventral to the aorta, shows a very small lumen, while that of the trachea is large and continued into the bronchi on either side. Adjacent to the esophagus are the cut vagus nerves. The lung anlages project laterally into the crescentic pleural cavities, of which the left is separated from the peritoneal cavity by the septum transversum. The liver, with its fine network of trabecule and sinusoids, is large and nearly fills the peritoneal or abdominal cavity. The liver cords are composed of liver cells surrounded by the endothelium of the sinusoids. Red blood cells are developed in the liver at this stage. The large vein penetrating the septum transversum from the liver to the heart is the proximal portion of the inferior vena cava, originally the right vitelline vein. Ventral to the bronchi may be seen sec- tions of the pulmonary veins. 132 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS Spinal ganglion Spinal nerve Notochord Post. cardinal vein Mesonephios Dorsal aorta Esophagus Pleural cavily ¢ Bifurcation of trachea Upper limb bud Inferior vena cava Fic. 136.—Transverse section through the liver and upper limb buds of a 10 mm. pig embryo at the level of the bifurcation of the trachea. X 22.5. Spinal cord Notochord Descending aorta . ° . & Sympathetic ganglion Mesone phros : ; Post. cardinal vein R. lung bud, , AMesonephric tubule Esophagus / Peritoneal cavity Lesser peritoneal sac raansal tobe of ite Inferior vena cava Vy § ‘e Tee ly Simusotds of liver Duclus venosus Fic. 137.—Dorsal half of a transverse section through the lung buds cranial to the stomach in a 10 mm. pig embryo. X 22.5. : Section through Lung Buds Cranial to Stomach (Fig. 137).—The lungs are sec- tioned through their caudal ends and the esophagus is just beginning to dilate into the TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO 133 stomach. On either side of the circular dorsal aorta are the mesonephroi, while dorso-laterally are sympathetic ganglia. The pleural cavities now communicate freely on both sides with the peritoneal cavity. A section of the lesser peritoneal sac appears as a crescent-shaped slit at the right of the esophagus. In the right dorsal lobe of the liver is located the inferior vena cava. Near the median line ventral to the lesser sac is the large ductus venosus. Section through the Stomach and Liver (Fig. 138).—Prominent in the body cav- ity are the mesonephroi and liver lobes. The mesonephroi show sections of coiled tubules lined with cuboidal epithelium. The glomeruli, or renal corpuscles, are median in position and develop as knots of small arteries which grow into the ends of the tubules. The thickened epithelium along the median and ventral surface of the mesonephros is the anlage of the genital gland. The body wall is thin and lined with mesothelium continuous with that which covers Spinal cord Spinal ganglion Notochord Dorsal aorla Glomerulus of mesonephros Plica vene cave Greater omentum Inferior vena cava e a Stomach Lesser omentum Fic. 138.—Transverse section through the stomach and liver of a 10 mm. pig embryo. X 22.5. the mesenteries and organs. The mesothelial layer becomes the epithelium of the adult peri- toneum, mesenteries, and serous layer of the viscera. The stomach lies on the left side and is attached dorsally by the greater omentum, ventrally to the liver by the Jesser omentum. The right dorsal lobe of the liver is attached dorsally to the right of the great omentum. Inthe liver, ventral to this attachment, courses the inferior vena cava and the attachment forms the plica vene cave. Between the attachments of the stomach and liver, and to the right of the stomach, is the lesser peritoneal sac. In the liver to the left of the midline is the ductus venosus, sectioned just at the point where it receives the left umbilical vein and a branch from the portal vein. The ventral attachment of the liver later becomes the falciform ligament. Section through the Hepatic Diverticulum (Fig. 139).—The section passes through the pyloric end of the stomach and duodenum near the attachment of the hepatic divertic- 134 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS ulum. The great omentum of the stomach is larger than in the previous section and to its right, in the plica vene cave, lies the inferior vena cava. Ventral to the inferior vena cava is a section of the portal vein. The ventral and dorsal lobes of the liver are now separate and in the right ventral lobe is embedded the saccular end of the hepatic diverticulum which forms the gall bladder. To the right of the stomach, the diverticulum is sectioned again just as it enters the duodenum. Ventrally the left umbilical vein is entering the left ventral lobe of the liver. It is much larger than the right vein, which still courses in the body wall. On the left side of the embryo the spinal nerve shows in addition to its dorsal and ventral rami a sym- pathetic ramus, the fibers of which pass to a cluster of ganglion cells located dorso-lateral to the aorta. These cells form one of a pair of sympathetic ganglia and are derived from a spinal ganglion. Spinal cord Notlochord —-+}$ ; Sym pathetic ramus Dorsal aorta Plica vene cave Dorsal mesogastrium Inferior vena cava Lesser peritoneal sav Portal vein Hepatic diverticulun L. umbilical vein R. umbilical vein Fic. 139.—Transverse section through the hepatic diverticulum of a 10 mm. pig embryo. X 22.5. Section through the Pancreatic Anlages (Fig. 140).—The lesser peritoneal sac just above the level of this section has opened into the peritoneal cavity through the cpiploic foramen (of Winslow). The mesonephric ducts are now prominent ventrally in the meso- nephroi. The duct of the dorsal pancreas is sectioned tangentially at the point where it takes origin from the duodenum. From the duct the lobulated gland may be traced dorsad in the mesentery. To the right of the dorsal pancreatic duct is a section of the ventral pancreas, which may be traced cephalad in the series to its origin from the hepatic diverticulum. Dorsal to the ventral pancreas is a section of the portal vein. The inferior vena cava appears as a vertical slit in the dorsal mesentery. Section through the Urogenital Sinus and the Lower Limb Buds (Fig. 141).— .The figure shows only the caudal end of a section, in the dorsal portion of which the meso- . TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO 135 nephroi were sectioned at the level of the subcardinal anastomosis. A portion of the mesentery is shown with a section of the colon. In the body wall are veins which drain into the umbilical veins, and on each side are the wmbilical arteries, just entering the body from the umbilical cord. Between them, in sections cranial to this, the allantoic stalk is located, Here it has opened into the crescentic urogenital sinus. Dorsal to the urogenital sinus (dorsal now being Post. cardinal vein R. vitelline or portal vein—¥ Mesonephric duct Ventral pancreas Fic. 140.—Portion of a transverse section through the pancreatic anlages of a 10 mm. pig embryo. x 22.5. at the bottom of the figure owing to the curvature of the caudal region) is a section of the rectum, separated from the sinus by a curved prolongation of the coelom. From the ends of the urogenital sinus, as we trace cephalad in the embryo (downward in the series), are given off the mesonephric ducts. Vein in body wall L. umbilical artery Allantois and urogenital sinus Mesonephric duct Fic. 141.—Transverse section through the urogenital sinus and rectum of a 10 mm. pigembryo. X 22.5. Section through the Mesonephric Ducts at the Opening of the Ureter (Fig. 142). —The section cuts through both lower limb buds near their middle. Mesial to their besas are the umbilical arteries, which lie lateral to the mesonephric ducts. From the dorsal wall of the left mesonephric duct is given off the ureter or duct of the metanephros. Tracing the sec- tions down in the series, both ureters appear as minute tubes in transverse section. They 136 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS soon dilate to form the pelvis of the kidney at the level of Fig. 143. Note the undifferentiated mesenchyme of the lower limb buds and their thickened ectodermal tips. Caudal limb of intestine Lower limb bud R. umbilical ariery Mesonephric duct Ureler Notochord Spinal cord Frc. 142,—Transverse section of a 10 mm. embryo passing through the lower limb buds at the level of the openings of the ureters into the mesonephric ducts. X 22.5. Section through the Metanephroi and Umbilical Arteries (Fig. 143).—The sec- tion passes caudal to the mesonephric ducts which curve along the ventral surfaces of the Calom Anlage of metanephros Vein Nolochord Spinal cord Fic. 143.—Transverse section through the anlages of the metanephroiina 10mm. pigembryo. X 22.5. mesonephroi (Fig. 124). The umbilical arteries course lateral to the metanephroi which con- sist merely of the thickened epithelium of the pelvis surrounded by a layer of condensed mesenchyma, the nephrogenic tissue. CHAPTER VI THE DISSECTION OF PIG EMBRYOS: DEVELOPMENT OF FACE, PALATE, TONGUE, SALIVARY GLANDS AND TEETH THE DISSECTION OF PIG EMBRYOS As the average student will not have time to study series of embryos sectioned in differ- ent planes, dissections may be used for showing the form and relations of the organs. Cleared embryos mounted whole are instructive, but show the structures superimposed and are apt to confuse the student.. Pig embryos 10 mm. or more in length may be easily dissected, mounted as opaque objects, and used for several years. Success in dissecting such small embryos de- pends: (1) on the fixation and hardenirig of the material employed; (2) on starting the dissec tion with a clean cut in the right plane; (3) on a knowledge of the anatomy of the parts to be dissected. Fixation and Hardening of Material—Embryos fixed in Zenker’s fluid have given the best results. They should then be so hardened in 95 per cent. alcohol that the more diffuse mesenchyma will readily separate from the surfaces of the various organs, yet the organs must not be so brittle that they will crumble and break. Embryos well hardened and then kept for two weeks in 80 per cent. alcohol usually dissect well. Old material is usually too brittle; that just fixed and hardened may prove too soft. As a test, determine whether the mesenchyma separates readily from the cervical ganglia and their roots. Dissecting instruments include a binocular dissecting microscope, a sharp safety razor blade, large curved blunt-pointed dissecting needles, pairs of small sharp-pointed for- ceps, and straight dissecting needles small and large. Methods of Dissection.—In general, it is best to begin the dissection with a clean, smooth cut ‘made by a single stroke with the safety razor blade, which should be flooded with 80 per cent. alcohol. The section is made free hand, holding the embryo, protected by a fold of absorbent cotton, between the thumb and index finger. Having made preliminary cuts in this way, the embryo may be affixed with thin celloidin to a cover glass and im- mersed in a watch glass containing alcohol. We prefer not to affix the embryo, as the celloidin used for this purpose may interfere with the dissection. Instead, a cut is made parallel to the plane of the dissection so that the embryo, resting in the watch glass upon this flat surface, will be in a fairly stable position. It may thus be held in any convenient position by resting the convex surface of a curved blunt dissecting needle upon some part not easily injured. The dissection is then carried on under the binocular microscope, using the fine pointed for- ceps, dissecting needles, and a’small pipette to wash away fragments of tissue. Whole Embryos.—For the study of the exterior, whole embryos may be affixed with celloidin to the bottoms of watch glasses which may be stacked in wide-mouthed jars of 80 per cent. alcohol. The specimens may thus be used several years at a saving of both time and material. Preliminary treatment consists in immersion in 95 per cent. alcohol one hour, in ether and absolute alcohol at least thirty minutes, in thin celloidin one hour or more. Pour enough thin celloidin into a Syracuse watch glass to cover its bottom, and immerse in this a circle of black mat paper, first wet with ether and absolute alcohol. Pour off any surplus cel- loidin, mount embryo in desired position and immerse watch glass in 80 per cent. alcohol, 137 138 THE DISSECTION OF PIG EMBRYOS in which the specimen may be kept indefinitely. Embryos may also be mounted in gelatin- formalin solution in small sealed glass jars. Lateral Dissections of the Viscera.—Dissections like those shown in Figs. 144 and 145 may easily be prepared in less than an hour, and make valuable demonstration and laboratory specimens. Skill is required to demonstrate most of the cerebral nerves, but the Mesencephalon N. oculomotorius Cerebellum N. trochlearis Gang. geniculatum n. 7 Gang. acust. n. 8 Gang. sup. n. 9 Gang. accessor. \ gS bs 4 Gang. jugulare n. 10 Gang. petrosum n. 9 N. hypoglossus Cerebrum Maxillary ramus n. 5 N. accessorius ~Chord.tymp. n. 7 Gang. cerv. NV. facialis | Gang. nodos. n. 10 Brachial plexus— I Lungs R. atrium R. ventricle Diaphragm q Q lf ( Nie ey y Ventral lobe of liver Dorsal lobe of liver 4. Umbilical cord Es “ \ (( Mesonephros e “SS \Z Scialic nerve Fic. 144.—Lateral dissection of an 18 mm. pig embryo, showing the nervous system and viscera from the right side. X 8. central nervous system, cerebral and spinal ganglia, and viscera may easily be exposed. Starting dorsally, make a sagittal section of the embryo slightly to one side of the median line and avoiding the umbilical cord ventrally. With the embryo resting on the flat sectioned surface, begin at the cervical flexure and with fine forceps grasp the ectoderm and dural anlage at its cut edge, separate it from the neural tube and pia mater, and strip it off ventralwards LATERAL DISSECTIONS OF THE VISCERA 139 exposing the myelencephalon and cervical portion of the cord. As the mesenchyma is pulled away, the ganglia and roots of the cerebral nerves will be exposed. The mesenchyma be- tween the ganglia and along the nerves may be removed with the end of a small blunt needle. Care must be exercised in working over the mesencephalon and telencephalon of the brain not Semilunar ganglion n. 5 Ophthalmic ramus n. 5 Geniculale gang. n. 7 Cerebrum gh Hoppin 4 . oplicus AMesencephalon Cerebellum Lobus olfactorius Gang. n. 8 Maxillary ramus n. Gang. sup. n. 9 2 Gang. jugulare n. ro Mand. ramus n. 5 Chorda. tymp. n. 7 Auricular r. n. 10 PN. facialis (7) Gang. n. cerv. I Gang. petros. n. 9 Ne ert Gin. nodosum n. IO N. hypoglossus Gang. cerv. 5-5 Gang. thor. 1 R. atrium R. ventricle Ventral lobe of liver = Umobil. cord Dorsal lobe of liver Mesonephros \/ o, ~Lower limb | Sciatic nerve Fre. 145.—Lateral dissection of a 35 mm pig embryo to show the nervous system and viscera from the right side. Xx 4. to injure the brain wall, which may be brittle. By starting with a clean dissection dorsally and gradually working ventrad, the more important organs may be laid bare without injury. The beginner should compare his specimen with the dissections figured and also previously study the reconstructions of Thyng (1911) and Lewis (1903). 140 THE DISSECTION OF PIG EMBRYOS Lateral dissections of embryos 18 mm. and 35 mm. long show infinitely better than sections the form and relations of the organs, their relative growth, and their change of position (Figs. 144 and 145). Compare the organs of 6, 10, 18, and 35 mm. embryos and note the rapid growth of the viscera (see Figs. 95 and 120). Hand-in-hand with the increased size of the viscera goes the diminution of the dorsal and cervical flecures. In the brain, note the increased size of the cerebral hemispheres of the telencephalon and the presence of the olfactory lobe of the rhinencephalon. The cerebellum also becomes prominent and a ventral flexure in the region of the pons, the pontine flexure, is more marked. The brain grows relatively faster than the spinal cord, and, by the elongation of their dorsal roots, the spinal ganglia are carried ventral to the cord. The body of the embryo also grows faster than the spinal cord, so that the spinal nerves, at first directed at right angles to the cord, course obliquely caudad in the lumbo-sacral region. Median Sagittal Dissections (Figs. 146 and 147).—Preliminary to the dissection, a cut is made dorsally as near as possible to the median sagittal plane. Beginning caudally at the mid-dorsal line, an incision is started which extends in depth through the neural tube and- the anlages of the vertebre. This incision is carried to the cervical flexure, cranial to which point the head and brain are halved as accurately as possible. The blade is then carried ventrally and caudally, cutting through the heart and liver fo the right of the midline and of the umbilical cord until the starting point is reached. A parasagittal section is next made well to the left of the median sagittal plane and the sectioned portion is removed, leaving on the left side of the embryo a plane surface. With the embryo resting upon this flat surface, the dissection is begun by removing with forceps the right half of the head. In pulling this away caudalwards, half of the dorsal body wall, the whole of the lateral body wall, and the parts of the heart and liver lying to the right of the midline will be removed, leaving the other struc- tures intact. Ifthe plane of section was accurate, the brain and spinal cord will be halved in the median sagittal plane. Wash out the cavities of the brain with a pipette and its internal structure may beseen. Dissect away the mesenchyma between the esophagus and trachea and expose the Jung. Remove the right mesonephros, leaving the proximal part of its duct attached to the urogenital sinus. The right dorsal lobe of the liver will overlie the stomach and pancreas. Pick it away with forceps and expose these organs. Dissect away the caudal portion of the liver until the hepatic diverticulum is laid bare. It is whitish in color and may thus be distinguished from the brownish liver. Beginning at the base of the umbilical cord, carefully pull away its right wall with forceps, thus exposing the intestinal loop and its attach- ment to the yolk stalk. If in the caudal portion of the umbilical cord the umbilical artery is removed, the allantoic stalk may be dissected out. To sce the anlage of the genital gland, break through and remove a part of the mesentery, exposing the mesial surface of the left mesonephros and the genital fold. The dissection of the metanephros and ureter is difficult in small embryos. In 10 to 12 mm. embryos, the umbilical artery, just after it leaves the aorta, passes lateral to the metanephros and thus locates it. By working carefully with fine needles the surface of the metanephros may be laid bare and the delicate ureter may be traced to the base of the mesonephric duct. The extent of the dorsal aorta may also be seen by removing the surrounding mesenchyma. With a few trials, such dissections may be made in MEDIAN SAGITTAL DISSECTIONS I41I a short time, and are invaluable in giving one an idea of the form, positions, and relations of the different organs. By comparing the early (Figs. 96 and 122) with the later stages (Figs. 146 and 147) a number of interesting points may be noted. Isthmus Mesencephalon Melencephaton Third ventricle Chorioid plexus of fourth ventricle Hy pothysis Diencephalon Tela chorioidea fourth ventricle a MM yelencephalon Cor pus striatum Epiglottis ~~ Cerebrum a ms a Ny Wy / Tongue Notochord Trachea — Aorta Trunk pulm. arlery— SAX Semilunar valves all) f V7] R. ventricle 4 |/ | ]/ Volk sac y ~~ Diaphragm ~ Volk stalk ~ Wall of atrium - Foramen ovale Esophagus Lung Dorsal aorta Liver ) Caecum Stomach Intersegmental Ue Se \ ‘ : arteries ZN Small intestine Pancreas " O4/ —= ———— Allantois Common bile duct ‘ ‘ ts , ~ . re ait Bladder Duodenum / ci Phallus en Genital fold < Urogenital sinus AMetanephros aS x Rectum Mesonephric duct Ureter Frc. 146.—Median sagittal dissection of an 18 mm. pig embryo, showing central nervous system in section and the viscera in position. X 8. In the brain, the corpus striatum develops in the floor of the cerebral hemi- spheres. The interventricular foramen is narrowed to a slit. In the roof of the diencephalon appears the anlage of the epiphysis, or pineal gland, and the chorioid plexus of the third ventricle. This extends into the lateral ventricles as the 142 THE DISSECTION OF PIG EMBRYOS lateral chorioid plecus. The dorso-lateral wall of the diencephalon thickens to form the thalamus and the third ventricle is narrowed to a vertical slit. The increased size of the cerebellum has been noted. Into the thin dorsal wall of the myelencephalon grows the network of vessels which form the chorioid plexus of Epiphysis Thalamus Mesencephaion Pedunculus cerebri Tela chorioidea Cerebellum Lat. chorioid plexus Chorioidal plexus ventricle 4 ‘pus striatum Tela of ventricle 4 Myelencephalon Hypo physis Lobus olfactorius Epiglottis PIs Turbinate anlage Esophagus Palate Spinal cord Tongue Trachea Aorta Pulmonary artery R. atri “ ne Ventricle R. bronchus Dorsal aorta Diaphragm \ Inf. vena cava ee Stomach Pancreas ‘ecum Gall bladder Small intestine Suprarenal gland Genital gland Duodenum Metanephros Urethra Colon L. mesonephric d Bladder Ureter me Urogenital sinus with mesonephric duct Rectum Fic. 147.—Median sagittal dissection of a 35 mm. embryo. X 4 the fourth ventricle, which is now spread out laterally and flattened dorso-ven- trally. About the notochord mesenchymal anlages which form the centra of the vertebre are prominent. Turning to the alimentary tract, observe that the primitive mouth cavity VENTRAL DISSECTIONS 143 is now divided by the palatine folds into the upper nasal passages and lower oral cavity. In the lateral walls of the nasal passages develop the anlages of the turbinate bones. On the floor of the mouth end pharynx, the tongue and epiglottis become more prominent. The trachea and esophagus elongate and the lungs lie more and more caudad. The dorsal portion of the septum transversum, the anlage of a portion of the diaphragm, is thus carried caudad, and although origi- nally, when traced from the dorsal body wall, it was directed caudad and ventrad, now it curves cephalad and ventrad, bulging cephalad into the thorax. The proximal limb of the intestinal loop elongates rapidly, and, beginning with the duodenum, becomes flexed and coiled in a characteristic manner. The distal limb of the intestinal loop is not coiled, but its diverticulum, the cecum, is more marked. Caudally, the rectum, or straight gut, has completely separated from the urogenital sinus and opens to the exterior through the anus. Of the urogenital organs, the genital folds have become the prominent genital glands attached to the median surfaces of the mesonephroi. The metanephror have increased rapidly in size and have shifted cephalad. Proximal to the allan- toic stalk the adjacent portion of the urogenital sinus has dilated to form the bladder. As the urogenital sinus grows it takes up into its wall the proximal ends of the mesonephric ducts, so that these and the ureters have separate openings into the sinus. Owing to the unequal growth of the sinus wall, the ureters open near the base of the bladder, the mesonephric ducts more caudally into the urethra. The phallus now forms the penis of the male or the clitoris of the female. Cranial to the metanephros a new organ, the suprarenal gland, has developed. This is a ductless gland and is much larger in human embryos. The heart, as may be seen by comparing Figs. 96 and 147, although at first pressed against the tip of the head, shifts caudally until, in the 35 mm. embryo, it lies in the thorax opposite the first five thoracic nerves. Later it shifts even further caudad. The same is true of the other internal organs, the metanephros excepted. As the chief blood vessels are connected with the heart and viscera, profound changes in the positions of the vessels are thus brought about, for the vessels must shift their positions with the organs which they supply. Ventral Dissections.—Ventral dissections of the viscera are very easily made. With the safety razor blade, start a cut in a coronal plane through the caudal end of the embryo and the lower limb buds (Fig. 148). Extend this cut laterad and cephalad through the body wall and the upper limb bud. The head may be cut away in the same plane of section, and the cut continued through the body wall and upper limb bud of the opposite side back caudally to the starting point. Section the embryo in a coronal plane, parallel with the first section and near the back, so that the embryo will rest upon the flattened surface. With 144 THE DISSECTION OF PIG EMBRYOS forceps now remove the ventral body wall. By tearing open the wall of the umbilical cord along one side it may be removed, leaving the intestinal loop intact. Pull away the heart, noting its external structure. The liver may also be removed, leaving the stomach and in- testine uninjured. A portion of the septum transversum covering the lungs may be care- fully stripped away and the lungs thus laid bare. Dissections made in this way show the trachea and lungs, the esophagus, stomach and dorsal attachment of the septum transversum, the course of the intestinal canal, and also the mesonephroi and their ducts. Favorable sections through the caudal end of the body may show the urogenital sinus, rectum, and ro SN | » Trachea fe Seplum transversum Midlerian duct anlage —— V — Stomach Caecum Mesoncphric duct “2 Mesonephros Large ie ~~ i : Umbilical artery Rectum Allantois — z Calom ~~ Fic. 148.—Ventral dissection of a 15 mm. pig embryo, showing lungs, digestive canal and mesonephroi. The ventral body wall, heart and liver have been removed and the limb buds cut across. X 6. sections of the umbilical arteries and allantois (Figs. 97, 124 and 148). In late stages, by removing the digestive organs, the urogenital ducts and glands are beau- tifully demonstrated (Figs. 223 and 224). DEVELOPMENT OF THE FACE The heads of pig embryos have long been used for the study of the development of the face. The heads should be removed by passing the razor blade between the heart and adja- cent surface of the head, thus severing the neck. Next cut away the dorsal part of the head by a section parallel to the ventral surface, the razor blade passing dorsal to the branchial clefts and eyes. Mount, ventral side up, three stages from embryos 6, 12, and 14 mm. long, as shown in Figs. 97 and 149. In the early stages (Figs. 97 and 124) the four branchial arches and clefts are seen. The third and fourth arches soon sink into the cervical sinus, while the mandibular processes of the first arch are fused early to form the iower jaw. Laterally the frontal process of the head is early divided into lateral and median DEVELOPMENT OF THE FACE 145 nasal processes by the development of the olfactory pits. The processes are dis- tinct and most prominent at 12 mm. (Fig. 149 A). Soon, in 13 to 14mm. embryos, the median nasal processes fuse with the maxillary processes of the first arch and constitute the upper jaw (Fig. 149 B). The lateral nasal processes fuse with the maxillary processes and form the cheeks, the lateral part of the lips, and the ale of the nose. Later, the median nasal processes unite and become the median part of the upper lip. Meanwhile the mesial remainder of the original frontal process (Fig. 149 A) is compressed and becomes the septum and dorsum of the nose. The development of the olfactory organ will be traced on p. 371. Lateral nasal process Olfactory pit —} Medial nasal process” 3 Mandible—< Eye Lacrimal groove —Maxillary process Branchial cleft I Branchial arch II 4 Nip f Ventral aorta | ipo m A - Branchial cleft II Lateral nasal process Maxillary process Medial nasal process Mandible Oral cavity Branchial cleft I 4 External ear Fic. 149.—Two stages showing the development of the face in pig embryos. X 7. A, Ventral view of face of a 12 mm. embryo; B, of a 14 mm. embryo. The early development of the face is practically the same in human embryos (Figs. 150 and 370). In embryos of 8 mm. the lateral and median nasal processes have formed. The maxillary processes next fuse with the nasal processes, after which the median nasal processes unite. Coincident with these changes the mandibular processes fuse and from them a median projection is developed which forms the anlage of the chin. Epithelial ingrowths begin to form the lips at the fifth week (Fig. 159). As the median nasal processes and the maxillary processes take part in their development, the failure of these © Io 146 THE DISSECTION OF PIG EMBRYOS parts to fuse may produce hare lip. The line of fusion of the median nasal processes is evi- dent in the adult as the philtrum. The lips of the newborn child are peculiar in that their proximal surfaces are covered with numerous villi, finger-like processes which may be a millimeter or more in length. \! Fic. 150.—Development of the face of the human embryo (His). A, Embryo of 8 mm. (X 7.5); the median frontal process differentiating into median nasal processes or processus globulares, toward which the maxillary processes of the first visceral arch are extending. B, Embryo of 13.7 mm. (X 5); the globular, lateral nasal and maxillary processes are in apposition; the primitive naris is now better defined. C, Embryo of 17 mm. (X 5); immediate boundaries of mouth are more definite and the nasal orifices are partly formed, external ear appearing. D, Embryo of nearly eight weeks (X 5). The external ear is developed around the first branchial cleft by the appearance of small tubercles which form the auricle. The cleft itself becomes the external auditory meatus and the concha of the ear. (For the development of the external ear see Chapter XIII.) DEVELOPMENT OF THE PALATE This may be studied advantageously in pig embryos of two stages: (a) 20 to 25 mm. long; (b) 28 to 35 mm. long. Dissections may be made by carrying a shallow incision from the anlage of the mouth back to the external ear on each side (Fig. 152). The incisions are then continued through the neck in a plane parallel to the hard palate. Before mounting the preparation, remove the top of the head by a section cutting through the eyes and nostrils. DEVELOPMENT OF THE PALATE 147 parallel to the first plane of section. Transverse sections through the snout may also be pre- pared to show the positions of tongue and palatine folds before and after the fusion of the latter (Fig. 151). In pig embryos of 20 to 25 mm. the jaws are close together and the mandible usually rests against the breast. Shelf-like folds of the maxille, the lateral pala- tine processes, are separated by the tongue and are directed ventrad (Figs. 151 A and 152 A). The median nasal processes also give rise to a single heart-shaped 2 Nasal septum ; Z j Tongue | i i) Lateral palatine process — Nasal septum “ Turbinate anlage as) Lateral palatine process ( Mandible —+ i ) \ he Poe. Fic. 151.—Sections through the jaws of pig embryos to show development of the hard palate. X 8. A, 22 mm.; B, 34 mm. structure, the median palatine process (Fig. 152). In embryos of 26 to 28 mm. the mandible drops, owing to growth changes, and the tongue is withdrawn from between the palatine processes (Fig. 151 B). With the withdrawal of the tongue the palatine folds bend upward to the horizontal plane, approach each other and fuse, thus cutting off the nasal passages from the primitive oral cavity (Fig. 152 B)- The primitive choane (cf. Fig. 153), formed by rupture of the membrane separating the olfactory pits from the oral cavity, now lead into the nasal passages, which in turn communicate with the pharynx by secondary permanent choane. At the 148 THE DISSECTION OF PIG EMBRYOS point in the median line where the lateral and median palatine processes meet, fusion is not complete, leaving the incisive fossa, and laterad between the two Median palatine process Raphé of lateral palatine process Median palatine process Lateral palatine process Internal choane ¥ Oral cavity Nasal passage Anlage of uvula — Fic. 152.—Dissections to show the development of the hard palate in pig embryos. X 5. A, Ventral view of palatine processes of a 22 mm. pig embryo, the mandible having been removed; B, Same of 35 mm. embryo showing fusion of palatine processes. processes openings persist for some time, which are known as the incisive canals (of Stenson). In human embryos these changes are essentially identical (Fig. 153). The lateral palatine processes begin to fuse cranio-caudally at about the end of the Frc. 153.—The roof of the mouth of a human embryo about two and a half months old, showing the development of the palate (after His). > 9. p.g., Processus globularis; p.g.’, palatine process of processus globularis; mx, maxillary process; mx’, palatine fold of maxillary process. Close to the angle between this and the palatine process of the processus globularis on each side are the prim- itive choane. second month. At the same time palatine bones first appear in the lateral pala- tine folds and thus form the hard palate. Caudally the bones do not develop @ DEVELOPMENT OF THE TONGUE 149 and this portion of the folds forms the soft palate and the wvila (Fig. 152). The unfused backward prolongations of the palatine folds give rise to the pharyngo- palatine arches, which are taken as the boundary line between the oral cavity proper and the pharynx in adult anatomy. After the withdrawal of the tongue, the lateral palatine processes take up a horizontal position and their edges are approximated because the cells on the ventral sides of the folds proliferate more rapidly than those of the dorsal side (Schorr, Anat. Hefte, Bd. 36, 1908). That the change in position of the palatine folds is not mechanical, but due to unequal growth, may be seen in Fig. 154, a section through the palatine folds of a pig embryo, which shows the Nasal sepium Lateral palatine process+ ‘Proliferating cells Lateral palatine process Tongue Fic. 154.—Section through the jaws of a 25 mm. pig embryo to show the change in the position of the palatine processes with reference to the tongue. right palatine fold in a horizontal position, although the left fold projects ventral to the dorsum of the tongue. A region of cellular proliferation may be seen on the under side of each process. Anomalies.—The lateral palatine processes occasionally fail to unite in the middle line, producing a defect known as cleft palaie. The extent of the defect varies considerably, in some cases involving only the soft palate, while in other cases both soft and hard palates are cleft. It may also be associated with hare lip. DEVELOPMENT OF THE TONGUE The development of the tongue may be studied from dissections of pig embryos 6, 9, and 13 mm. long. As the pharynx is bent nearly at right angles, it is necessary to cut away its roof by two pairs of sections passing in different planes. The first plane of section cuts through the eye and first two branchial arches just above the cervical sinus (Fig. 155, I). From the surface, the razor blade should be directed obliquely dorsad in cutting toward the median line. Cuts in this plane should be made from either side. In the same way make sections on each side in a plane forming an obtuse angle with the first section and passing dorsal to the cervical sinus (II). Now sever the remaining portion of the head from the body by a transverse section in a plane parallel to the first (III). Place the ventral portion of the head in a watch glass of alcohol, and, under the dissecting microscope, remove that part of the preparation cranial to the mandibular arches. Looking down upon the floor of the pharynx, remove any portions of the lateral pharyngeal wall which may still interfere with a clear view of the pharyngeal arches as seen in Figs. 98 and 156. Permanent mounts of the three stages mentioned above may be made and used for study by the student. 150 THE DISSECTION OF PIG EMBRYOS The tongue develops as two distinct portions, the body and the root, separated from each other by a V-shaped groove, the sulcus terminalis. In both human and pig embryos the body of the tongue is developed from three anlages which are formed in front of the second branchial arches. These are the median, somewhat triangular tuberculum impar, and the paired FF “ lateral swellings of the first, or mandibular, arches, both of which are present in human Fic. 155.—Lateral view of the head embryos of 5 mm. (Figs. 98 and 157 A). of « 7 mm. pig embryo. The three A+ this stage, a median ventral elevation lines indicate the planes of sections to be made in dissecting the tongue as de- formed by the union of the second branchial eee arches (and, according to some workers, the third as well) forms the copula. This, with the portions of the second arches lateral to it, forms later the base or root of the tongue. Between it and the (Be is Branchial arch My } Tuberculum impar < oR Branchial arch 2 - Branchial arch 3 ‘ ; Branchial arch 4 a E ‘a eee 3 Arytenoid ridge aa pels fe. a Sat j —_> lingual anlage —Copula Epiglottis Glottis Branchial arch r , . ; ‘il / oh ky = = Tuberculum impar Lateral lingual anlage —\— aie —— ay a Branchial arch 2 Branchial arch 3- ee ; on ‘ f Branchial arch 4 e a V : ‘ E piglottis Arytenoid ridge Glottis Fic. 156.—Dissections showing the development of the tongue in pig embryos. X 12. A, 9 mm. em- bryo; B, 13 mm. embryo. tuberculum impar is the point of evagination of the thyreoid gland. The copula also connects the tuberculum impar with a rounded prominence which is developed DEVELOPMENT OF THE TONGUE I5t in the mid-ventral line from the bases of the third and fourth branchial arches. This is the anlage of the epiglottis, In later stages (Fig. 156 A and B) the lateral mandibular anlages, bounded laterally by the alveolo-lingual grooves, increase rapidly in size and fuse with the tuberculum impar, which lags behind in develop- ment and is said to form the median septum of the tongue. According to Ham- mar, it atrophies completely. The epiglottis becomes larger and concave on its ventral surface. Caudal toit, and in early stages continuous with it, are two thick rounded folds, the arytenoid ridges. Between these is the slit-like glottis leading into the larynx (see p. 165). Lateral tongue swellings Thyreoid diverticulum Lateral tongue swellings Entrance to y_ Entrance to larynx larynx Arylenoid swellings A B Fic. 157.—The development of the tongue in human embryos. A, 5 mm.; B, 7 mm. (modified from Peters). The foregoing account applies to the early origin of the mucous membrane alone. The musculature of the tongue is supplied chiefly by the Aypoglossal nerve, and both nerve and muscles develop caudal to the branchial region in which the tongue develops. The muscu- lature migrates cephalad and gradually invades the branchial region beneath the mucous membrane. At the same time, the tongue may be said to extend caudad until its root is cov- ered by the epithelium of the third and fourth branchial arches. This is shown by the fact that the sensory portions of the nn. érigeminus and facialis, the nerves of the first and second arches, supply the body of the tongue, while the nn. glossopharyngeus and vagus, the nerves of the third and fourth arches, supply the root and the caudal portion of the body of the tongue. In fetuses of 50 to 60 mm. (C R) the fungiform and filiform papille may be dis- tinguished as elevations of the epithelium. Taste buds appear in the fungiform papille of 100 mm. (C R) fetuses and are much more numerous in the fetus than in the adult. The vallate papille (Fig. 158 A) appear as a V-shaped epithelial ridge, the apex of the V corresponding to the site of the thyreoid vagination (foramen cecum). At intervals along the epithelial ridges circular epithelial downgrowths develop (85 mm. C R) which take the form of inverted and hollow truncated cones (Fig. 158). During the fourth month circular clefts appear in the epithelial downgrowths, thus separating the walls of the vallate papilla from 152 THE DISSECTION OF PIG EMBRYOS the surrounding epithelium and forming the trench from which this type of papilla derives its name. At the same time, lateral outgrowths arise from the bases of the epithelial cones, hollow out and form the ducts and glands of Ebner. : ya ea cc yeas erabumueaaeee” Cc Fic. 158.—Diagrams showing the development of the vallate papille of the tongue (Graberg in McMur- rich). u, valley; b, von Ebner’s gland. The taste buds of the vallate papille are also formed early, appearing in embryos of three months. Foliate papille probably appear at about six months. DEVELOPMENT OF THE SALIVARY GLANDS The glands of the mouth are all regarded as derivatives of the ectodermal. epithelium. Their development has been studied recently by Hammar (Anat. Anz., Bd. 19, 1901) and by Schulte (Studies in Cancer etc., N. Y., vol. 4, 1913). Of the salivary glands, the parotid is the first to appear. Its anlage has been observed in 8 mm. embryos, near the angle of the mouth, as a keel-like flange in the floor of the alveolo-buccal (i. e. jaw-cheek) groove (Hammar). The flange elongates, and, in embryos of 17 mm., separates from the epithelial layer, form- ing a tubular structure which opens into the mouth cavity near the cephalic end of the original furrow. The tube grows back into the region of the external ear, branches, and forms the gland in this region, while the unbranched portion of the tube becomes the parotid duct. The submazillary gland arises at 11 mm. as an epithelial ridge in the alveolo- lingual (i. e. jaw-tongue) groove, its cephalic end located caudal to the frenulum of the tongue. The caudal end of the ridge soon begins to separate from the epi- thelium and extends caudad and ventrad into the submaxillary region, where it enlarges and branches to form the gland proper; its cephalic unbranched portion, persisting as the duct. soon hollows out. The sublingual and alveolo-lingual glands develop in 24 mm. embryos as several solid evaginations of epithelium from the alveolo-lingual groove (Fig. 163). Each group, usually regarded as a sublingual gland, really consists of the sublingual proper, with its ductus major, and of about ten equivalent alveolo-lingual glands. The solid branched anlages of the salivary glands last become hollow at their tips. The glands continue to differentiate until after birth. Mucin cells may be distinguished by the sixteenth week and acinus cells in the parotid glands at five months (McMurrich). DEVELOPMENT OF THE TEETH 153 DEVELOPMENT OF THE TEETH The enamel organs, which give rise to the enamel of the teeth and are the moulds, so to speak, of the future teeth, are of ectodermal origin. ‘There first ap- pears in embryos of about 11 mm. an ectodermal downgrowth, the dental ridge or lamina, on the future alveolar portions of the upper and lower jaws (Fig. 159). These laminz are parallel and mesial to the labial grooves. At intervals, on L Lower lip Mandible Dental lamina ~/_Labial groove Dental papilla Dental lamina A B Fic. 159.—Early stages in the development of the teeth (Rise). A,at 17mm. (X 90); B,at 41 mm. (X 45). each curved dental ridge or lamina a series of thickenings develop, the anlages of the enamel organs (Fig. 160). Soon the ventral side of each enamel organ be- comes concave (fetuses of 40 mm. C H) forming an inverted cup and the con- cavity is. occupied by dense mesenchymal tissue, the dental papilla (Tigs. 159 B and 162). An enamel organ with dental papilla forms the anlage of each decid- Dental groove Enamel organs Oral epithelium Free edge of the dental lamina tal lami en" \/ Dene denne Papille ce organs Necks of enamel organs A B Cc D Fic. 160.—Diagrams showing the early development of three teeth. One of the teeth is shown in vertical section (Lewis and Stohr). ual or milk tooth. Ten such anlages are present in the upper jaw and ten in the lower jaw of a 40 mm. fetus. The connection of the dental anlages with the dental ridge is eventually lost. The position of the tooth anlage between the tongue and lip is shown in Fig. 163. 154 THE DISSECTION OF PIG EMBRYOS The anlages of those permanent teeth which correspond to the decidual, or milk teeth, are developed in another series along the free edge of the dental Labial groove Dental lamina Milk molar I Aboral prolonga- tion of dental lamina Fic. 161.—Dental lamina and anlages of the milk teeth of the upper jaw from a fetus of 115 mm (Rése in Kollmann). Dental lamina ~—Epidermis Outer enamel layer Enamel pulp Inner enamel layer Dental papilla me al Fic. 162.—Section through the upper first decidual incisor tooth froma 65 mm. human fetus. X 70. lamina (Fig. 160 D) and come to lie mesad of the decidual teeth. In addition, the anlages of three permanent molars are developed on each side, both above and below, from a backward or aboral extension of the dental lamina, entirely DEVELOPMENT OF THE TEETH 155 free from the oral epithelium (Fig. 161). The anlages of the first permanent molars appear at seventeen weeks (180 mm. C H), those of the second molars at Tip of tongue Fp Epidermis of lip Sulouavitiorp dua ee gs = j Te Enamel organ of tooth ae = Sf Sublingual duct— ——+ Dental papilla Meckel’s cartilage Bone of mandible Fic. 163.—Parasagittal section through the mandible and tongue of a 65 mm. human fetus showing the position of the anlage of the first incisor tooth. X 14. six weeks after birth, while the anlages of the third permanent molars or wisdom teeth are not found until the fifth year. The permanent dentition of thirty-two teeth is then complete. Inner enamel layer (ameloblasts)~ \\\ Dentine and___ \ dentinal fibers Lape Sh Dental pulpe---- rhe (sc JB WOE Fic. 164.—Section through a portion of the crown of a developing tooth showing the various layers (after Tourneux in Heisler). The internal cells of the enamel organs are at first compact, but later by the development of an intercellular matrix the cells separate, forming a reticulum resembling mesenchyme, termed the enamel pulp (Fig. 162). The outer enamel 156 THE DISSECTION OF PIG EMBRYOS cells, at first cuboidal, flatten out and later form a fibrous layer. The inner enamel cells bound the cup-shaped concavity of the enamel organ. Over the crown of the tooth these cells, the ameloblasts, become slender and columnar in Dental sac ——-_ Outer layer — Inner layer \ a Outer enamel cells Enamel pulp \ Inner enamel cells \ ug (ameloblasts) Enamel Dentine Epithelial sheath ie eee Odontoblasts Dental papilla (fulure pulp) wz Blood vesse!” Bony trabecula of jaw— Fic. 165.—Longitudinal section of a deciduous tooth of a newborn dog. X 42. The white spaces between the inner enamel cells and the enamel are artificial and due to shrinkage (Lewis and Stéhr). form, producing the enamel layer of the tooth along their basal ends (Fig. 164). The enamel is laid down first an an uncalcified fibrillar layer which later becomes calcified in the form of enamel prisms one for each ameloblast. The enamel is formed first at the apex of the crown of the tooth and extends downward toward DEVELOPMENT OF THE TEETH 157 the root. The enamel cells about the future root of the tooth remain cuboidal or low columnar in form, come into contact with the outer enamel cells, and the two layers constitute the epithelial sheath of the root which does not produce enamel prisms (Fig. 165). The Dental Papilla.—The outermost cells of the dental papilla at the end of the fourth month arrange themselves as a definite layer of columnar epithelium. Since they produce the dentine, or dental bone, these cells are known as odonto- blasts (Fig. 165). When the dentine layer is developed, the odontoblast cells remain internal to it, but branched processes from them (the dentinal fibers of Tomes) extend into the dentine and form the dental canaliculi. Internal to the odontoblast layer, the mesenchymal cells differentiate into the dental pulp, pop- ularly known as the “nerve” of the tooth. This is composed of a framework of reticular tissue in which are found blood vessels, lymphatics, and nerve fibers. The odontoblast layer persists throughout life and continues to secrete dentine, so that eventually the root canal may be obliterated. Dental Sac.—The mesenchymal tissue surrounding the anlage of the tooth gives rise to a dense outer layer and a more open inner layer of fibrous connective tissue. These layers form the dental sac (Fig. 165). Over the root of the tooth a layer of osteoblasts or bone forming cells develops, and, the epithelial sheath formed by the enamel layers having disintegrated, these osteoblasts deposit about the dentine a layer of bone which is known as the substantia ossea or cement. The cement layer contains typical bone cells but no Haversian canals. As the teeth grow and fill the alveoli, the dental sac becomes a thin vascular layer, con- tinuous externally with the alveolar periosteum, internally with the periosteum of the cement layer of the tooth. When the crown of the tooth is fully developed the enamel organ disinte- grates, and, as the roots of the teeth continue to grow, their crowns approach the surface and break through the gums. The periods of eruption of the various milk or decidual teeth vary with race, climate, and nutritive conditions. Usually the teeth are cut in the following sequence: DECIDUAL OR MILK TEETH Median Incisorssic.s0228 es qavtewnaen reed ares sixth to eighth month. Lateral Incisors:..as.e..ssan cgowmewenne vas ee ee danse eighth to twelfth month. Hirst; Molarsy ao conti ce ace ucwencnawaeee toe tas twelfth to sixteenth month. Canines isc: sop is3.5 ciawalae bund aAguuaauigeeGl in Mosel seventeenth to twentieth month. Second MOlaTS i csctacaed cued tara UNNe EMEA ara ttleey twentieth to thirty-sixth month. The permanent teeth are all present at the fifth year. They are located mesial to the decidual teeth (Fig. 166), and, before the permanent teeth begin I 58 THE DISSECTION OF PIG EMBRYOS to erupt, the roots of the milk teeth undergo partial resolution, their dental pulp dies, and they are eventually shed. Toward the sixth year, before the shedding Permanent second molar ~—¥t\: Permanent premolars Mental foramen Permanent canine smell Permanent incisors Fic. 166.—The skull of a five-year-old child showing positions of the decidual and permanent teeth (Sobotta~-McMurrich). of the deciduous teeth begins, each jaw may contain twenty-six teeth. The permanent teeth are “cut” as follows (McMurrich in Keibel and Mall, vol. 2) Pirst MGlates. 9. o0'sieran ssiey see ey eeenecomin sad eaieahnd seventh year. Median: In¢isors. sider eye age cee eta os geal eighth year. Lateral AnCisOrsis if sccgaseee ee ia eae a 4 mE ninth year. First Premolarss.3.2 Qeecang ae se ede a gectneede Ga eRS tenth year. Second Premolars - 0.0... 0c cco cn ba eee ha eee es eleventh year. Ss aes ne £8 GAHAN d Ray Ea ieee Sa Se US thirteenth to fourteenth year. Third Molars (Wisdom Teeth)...................-. seventeenth to fortieth year. The teeth of vertebrates are homologues of the placoid scales of elasmobranch fishes (sharks and skates). The teeth of the shark resemble enlarged scales, and many generations of teeth are produced in the adult fish. In some mammalian embryos three or even four dentitions are present. The primitive teeth of mammals are of the canine type, and from this conical tooth the incisors and molars have been differentiated. Anomalies.—Dental anomalies are frequent and may consist in the congenital absence of some or all of the teeth, or in the production of more than the normal number. Defective teeth are frequently associated with hare lip. Cases have been noted in which, owing to defect of the enamel organ, the enamel was entirely wanting. Many cases in which a third dentition occurred have been recorded and occasionally fourth molars may be developed behind the wisdom teeth. CHAPTER VII THE ENTODERMAL CANAL AND ITS DERIVATIVES: THE BODY CAVITIES WHEN the head- and tail folds of the embryo develop, there are formed both cranial and caudal to the spherical vitelline sac blind entodermal tubes, the Sore- gut ana hind-gut respectively (Figs. 79 and 167 A). The region between these intestinal tubes, open ventrally into the yolk sac, is sometimes termed the mid-gut. Pharynx Pharyngeal Pharynx membrane Pharyngeal Thyreoid-_” fg membrane gland y Pericardial Pericardial cavily cavily Fore gut ete Hepatic diverticulum _ Hepatic diverticulum Yolk stalk Volk stalk Hind-gut Cloacal Allantois membraie Allantois a Cloacal Cloaca membrane Cloaca Hind-gut Fic. 167.—Diagrams showing in median sagittal section the human alimentary canal, pharyngeal and cloacal membranes. X 35. A, 2 mm. embryo (modified after His); B, 2.5 mm. embryo (after Thompson). As the embryo and the yolk sac at first grow more rapidly than the connecting region between them, this region is apparently constricted and becomes the yolk stalk or vitelline duct. At either end the entoderm comes into contact ven- trally with the ectoderm. Thus there are formed the pharyngeal membrane of the 159 160 THE ENTODERMAL CANAL AND THE BODY CAVITIES fore-gut, the cloacal membrane of the hind-gut. In 2 mm. embryos the pharyngeal | membrane separates the ventral ectodermal cavity, or stomodeum, from the pharyngeal cavity of the fore-gut. Cranial to the membrane is the ectodermal diverticulum, Rathke’s pocket. In 2.5 to 3 mm. embryos (Fig. 167 B) the pharyngeal membrane ruptures and the stomodeum and pharynx become continuous. The blind termination of the fore-gut apparently forms Seessel’s pocket. The fore-gut later forms part of the oral cavity and is further differentiated into the pharynx and its derivatives, and into the esophagus, respiratory organs, stomach, duodenum, jejunum, and a portion of the ileum. From the duodenum arise the liver and pancreas. The hind-gut, beginning at the attachment of the yolk stalk extends caudally to the cloaca, into which the allantois opens in 2 mm. embryos. The hind-gut is differentiated into the ileum, cecum, colon, and rec- tum. The cloaca is subdivided into the rectum and urogenital sinus (for its de- velopment see Chapter VIII). At the same time the cloacal membrane is separated into a urogenital membrane and into an anal membrane. The latter eventually ruptures, forming the awus. The yolk stalk usually loses its connec- tion with the entodermal tube in embryos of about 7 mm. (Fig. 179). We have seen how the palatine processes divide the primitive oral cavity into the nasal passages and mouth cavity of the adult, and have described the development of the tongue, teeth, and salivary glands—organs derived wholly or in part from the ectoderm. It remains to trace the development of the pharynx and the intestinal tract and their derivatives. PHARYNGEAL POUCHES There are developed early from the lateral wall of the pharynx paired out- growths which are formed in succession cephalo-caudad. In 4 to 5 mm. embryos, five pairs of such pharyngeal pouches are present, the fifth pair being rudimentary (Figs. 86 and 87). Meantime, the pharynx has been flattened dorso-ventrally and broadened laterally and cephalad, so that it is triangular in ventral view (Figs. 87 and 168). From each pharyngeal pouch develop small dorsal and large ventral diver- ticula. All five pouches come into contact with the ectoderm of the branchial clefts, fuse with it, and form the closing plates. Only occasionally do the closing plates become perforate in human embryos. The first and second pharyngeal pouches soon connect with the pharyngeal cavity through wide openings. The third and fourth pouches grow laterad and their diverticula communicate with PHARYNGEAL POUCHES 1601 the pharynx through narrow ducts in 10 to 12 mm. embryos (Fig. 168). When the cervical sinus (p. 97) is formed, the ectoderm of the second, third, and fourth branchial clefts is drawn out to produce the transient branchial and cervical ducts and the cervical vesicle. These are fused at the closing plates with the entoderm of the second, third, and fourth pharyngeal pouches. The first and second pouches soon differ from the others in form, and give rise to an entirely different type of permanent structures. With the broadening of Branchial duct 2 Epithelial body of 34 pouch Pharyngeal pouch 1 Branchial cleft 1 Pharyngeal pouch 2 Gorvital sins Pharyngeal pouch 3 Cervical vesicle Thymus anlage Epithelial body of 4th pouch Pharyngeal pouch 4 Pharyngeal pouch 5 Esophagus Trachea hag 5 A pical bud of right lung Gall bladder Duodenum Fic. 168.—A reconstruction of the pharynx and fore-gut of an 11.7 mm. human embryo seen in dorsal view (after Hammar). The ectodermal structures are stippled. the pharynx the first two pouches acquire a common opening into it. The first pouch later differentiates into the tympanic cavity of the middle ear and into the auditory (Eustachian) tube. By the growth and lateral expansion of the pharynx, the second pouch is absorbed into the pharyngeal wall, its dorsal angle alone persisting, to be later transformed into the tonsillar and supratonsillar fosse. The third, fourth, and fifth pouches give rise to a series of ductless glands,-the thymus, parathyreoids, and the ultimobranchial bodies. Ir 162 THE ENTODERMAL CANAL AND THE BODY CAVITIES A mound of lymphoid tissue presses against the epithelium of the tonsillar fossa in 140 mm. (C R ?) fetuses and forms the palatine tonsil. The lymphocytes are probably of mesodermal origin (Hammar, Maximow). Imperfect closure of the branchial clefts (usually the second) leads to the formation of cysts, diverticula, or even of fistula. According to Hammar (Arch. f. mikr. Anat., Bd. 61, 1903), the lateral pharyngeal recess (of Rosenmuller) is not a persistent portion of the second pouch as His asserted. A subepithelial infiltration of lymphocytes during the sixth month gives rise to the median pharyngeal tonsil, which like the lingual tonsil is not of pharyngeal pouch origin. Immediately caudad is a recess, the pharyngeal bursa, formed by a persistent connection of the epithelium with the notochord (Huber). THE THYMUS The thymus anlage appears in 10 mm. embryos as a ventral and medial prolongation of the third pair of pouches (Figs. 168 and 169). The ducts con- necting the diverticula with the pharynx soon disappear so that the thymus an- lages are set free. At first hollow tubes, they soon lose their cavities and their Foramen cecum Thyreoid anlage Thymus anlages Post-branchial body Fic. 169.—Diagram in ventral view of the pharynx and pharyngeal pouches, showing the origin of the thymus and thyreoid glands and of the epithelial bodies (modified after Groschuff and Kohn). J-V, first to fifth pharyngeal pouches. lower ends enlarge and migrate caudally into the thorax, passing usually ven- tral to the left vena anonyma. Their upper ends become attentuate and atrophy, but may persist as an accessory thymus lobe (Kohn). The enlarged lower ends of the anlages form the body of the gland, which is thus a paired structure (Fig. 170). At 50 mm. (C R) the thymus still contains solid cords and small closed vesicles of entodermal cells. From this stage on, in development, the gland becomes more and more lymphoid in character. Its final position is in the thorax, dorsal to the cranial end of the sternum. It grows under normal conditions until puberty, THE EPITHELIAL BODIES OR PARATHYREOIDS 163 after which its degeneration begins. This process proceeds slowly in healthy individuals, rapidly in case of disease. The thymus may function normally until after the fortieth year. The ventral diverticulum of the fourth pouch is a rudimentary thymic anlage. It usually atrophies. It is now generally believed that the entodermal. epithelium of the thymus is converted into reticular tissue and thymic corpuscles. The “lymphoid” cells are regarded by Hammar, Maximow, and recently by Badertscher (Amer. Jour. Anat., vol. 17, 1915) as immigrant Jugular Carotid Carotid vein artery artery Thyreoid Parathyreoid IV. Parathyreoid III. Thyreoid Parathyreoid IV. Parathyreoid III. Fic. 170.—Reconstruction of the thymus and thyreoid glands in a 26 mm. human embryo (after Tourneaux and Verdun). X 15. lymphocytes derived from the mesoderm. According to Stéhr, they are not true lympho- cytes, but are derived from the thymic epithelium. Weill (Arch. f. mikr. Anat., Bd. 83, 1913) has observed the development of granular leucocytes in the human thymus gland. THE EPITHELIAL BODIES OR PARATHYREOIDS The dorsal diverticula of the third and fourth pharyngeal pouches each give rise to a small mass of epithelial cells termed an epithelial body (Fig. 169). Two pairs of these bodies are thus formed, and, with the atrophy of the ducts of the pharyngeal pouches, they are set free and migrate caudalward. They eventually lodge in the dorsal surface of the thyreoid gland, the pair from the third pouch lying one on each side at the caudal border of the thyreoid in line with the thymus anlages (Fig. 170). The pair of epithelial bodies derived from the fourth pouches are located on each side near the cranial border of the thyreoid. From their ultimate relation to the thyreoid tissue the epithelial bodies are often termed parathyreoid glands. The solid body is broken up into masses and cords of poly- gonal entodermal cells intermingled with blood vessels. In postfetal life, lumina may appear in the cell masses and fill with a colloid-like secretion. 164 THE ENTODERMAL CANAL AND THE BODY CAVITIES THE ULTIMOBRANCHIAL OR POSTBRANCHIAL BODIES The ultimobranchial body is the derivative of the fifth pharyngeal pouch (Fig. 169). With the atrophy of the duct of the fourth pouch it is set free and migrates caudad with the parathyreoids. It forms a hollow vesicle which has been erroneously termed the lateral thyreoid. According to Grosser (Keibel and Mall, vol. 2) and Verdun, it takes no part in forming thyreoid tissue, but atrophies. Kingsbury (Anat. Anz., Bd. 47, 1915) denies the origin of the ultimobranchial body from any specific pouch, and asserts it is “merely formed by a continued growth activity in the branchial entoderm.” THE THYREOID GLAND In embryos with five to six primitive segments (1.4 mm.) there appears in the mid-ventral wall of the pharynx, between the first and second branchial arches, a small out-pocketing, the thyreoid anlage. In 2.5 mm. embryos it has become a stalked vesicle (Figs. 167 B and 87) Its stalk, the t#yreoglossal duct, opens at the aboral border of the tuberculum impar of the tongue (Fig. 157 A); this spot is represented permanently by the foramen caecum (Fig. 180). The duct soon atrophies and the bilobed gland anlage (Fig. 169) loses its lumen and breaks up into irregular solid anastomosing plates of tissue as it migrates caudad. It takes up a transverse position with a lobe on each side of the trachea and larynx (Fig. 170). In embryos of 24 mm. discontinuous lumina begin to appear in swollen portions of the plates; these represent the primitive thyreoid follicles (Norris, Amer. Jour. Anat., vol. 20, 1916). LARYNX, TRACHEA AND LUNGS In embryos of 23 segments, the anlage of the respiratory organs appears as a groove in the floor of the entodermal tube just caudal to the pharyngeal pouches. This groove produces an external ridge on the ventral wall of the tube, a ridge which becomes larger and rounded at its caudal end (Fig. 171). The laryngo- tracheal groove and the ridge are the anlages of the larynx and trachea. The rounded end of the ridge is the unpaired anlage of the lungs. Externally two lateral longitudinal grooves mark off the dorsal esophagus from the ventral respiratory anlages. The lung anlage rapidly increases in size and becomes bilobed in embryos of 4 to 5 mm. A fusion of the lateral furrows progressing cephalad, constricts first the lung anlages and then the trachea from the esophagus. At the same time the laryngeal portion of the groove and ridge advances cranially until it lies between the fourth branchial arches (Fig. 87). At LARYNX, TRACHEA AND LUNGS 165 5 mm. the respiratory apparatus consists of the laryngeal groove and ridge, the tubular trachea, and the two lung buds (Fig. 165 D). The Larynx.—In embryos of 5 to 6 mm. the oral end of the laryngeal groove is bounded on either side by two rounded prominences, the arytenoid swellings, which, continuous orally with a transverse ridge, form the furcula of His (Fig. 157 B). The transverse ridge becomes the epiglottis, and, as we saw in connec- tion with the development of the tongue, it is derived from the third and fourth branchial arches. In embryos of 15 mm. the arytenoid swellings are bent near the middle. Their caudal portions become parallel, while their cephalic portions aA B Cc Trachea Respiratory anlage ——Lung bud — Esophagus Esophagus D E Trachea Trachea Apical bud Primary bronchus Ventral bud € Fic. 171.—Diagrams of stages in the early development of the trachea and lungs of human embryos (based on reconstructions by Bremer, Broman, Grosser, and Narath). X about 50. A, 2.5mm; B, 4mm; C, stage B in side view; D, 5 mm.; E, 7 mm. diverge nearly at right angles (Fig. 172). The opening into the larynx thus be- comes T-shaped and ends blindly, as the laryngeal epithelium has fused. In 40 mm. fetuses (C R) this fusion is dissolved, the arytenoid swellings are withdrawn from contact with the epiglottis, and the entrance to the larynx becomes oval in form (Fig. 173). At 27 mm. the ventricles of the larynx appear and at 37 mm. (C R) their margins indicate the position of the-vocal cords. The epithelium of the vocal cords is without cilia. The elastic and muscle fibers of the cords are developed by the fifth month. At the end of the sixth week the cartilaginous skeleton of the larynx is indicated by sur- rounding condensations of mesenchyme. The cartilage of the epiglottis appears relatively 166 THE ENTODERMAL CANAL AND THE BODY CAVITIES late. The thyreoid cartilage is formed as two lateral plates, each of which has:two centers of chondrification. These plates grow ventrad and fuse in the median line. The anlages of the cricoid and arytenoid cartilages are at first continuous. Later, sepa- rate cartilage centers develop for the arytenoids. The cricoid is at first incomplete dorsad, but eventually forms a complete ring. The cricoid may therefore be regarded as a modified tracheal ring. The cornic- ulate cartilages represent separated por- _ pl.ph.e.---- tions of the arytenoids. The cuneiform cartilages are derived from the cartilage ot es of the epiglottis. cun. 4 ------ corn, ft. ee Fic. 172.—Entrance to larynx in a 15 to 16 Fic. 173.—The larynx of 160 to 230 mm. mm. human embryo (from Kallius). x 15. 4, human fetuses (Soulié and Bardier). 6. From Tuberculum impar; ~, pharyngo-epiglottic fold; a dissection. 06., Base of tongue; ¢., epiglottis; e, epiglottic fold; /.e, lateral part of epiglottis; f.z.a., interarytenoid fissure; 0./., orifice of larynx; cun., cuneiform tubercle; corn., corniculate tu- pl.a.e., plica ary-epiglottica; pl.ph.e., plica phar- bercle. yngo-epiglottica; cun., cuneiform tubercle; corn., corniculate tubercle. The Trachea.—This gradually elongates during development and its colum- nar epithelium becomes ciliated. Muscle fibers and the anlages of the cartilag- Fic. 174.—Ventral and dorsal views of the lungs from a human embryo of about 9 mm. (after Merkel). Ap., Apical bronchus; Dr, D2, etc., dorsal, Vz, V2, etc., ventral bronchi; Jc., infracardial bronchus. inous rings appear at 17mm. The glands develop as ingrowths of the epithelium during the last five months of pregnancy. LARYNX, TRACHEA AND LUNGS 107 The Lungs.—Soon after the lung anlages or stem buds are formed (in 5 mm. embryos), the right bronchial bud becomes larger and is directed more caudally (Fig. 171). At 7 mm. the stem bronchi give rise to two bronchial buds on the right side, to one on the left. The smaller bronchial bud on the right side is the apical bud. The right and left chief buds, known as ventral bronchi, soon bifur- cate. There are thus formed three bronchial rami on the right side, two on the left, and these correspond to the primitive lobes of the lungs (Fig. 174). On the left side, an apical bud is interpreted as being derived from the first ventral bron- chus (Fig. 174). It develops later and remains small so that a lobe corresponding to the upper lobe of the right lung is not developed (Narath). The upper lobe of the left lung thus would correspond to the upper and middle lobes of the right lung. Mediastinum + Parietal pleura Pleuro-peritoneal membrane Pleural cavity Pleuro-peritoneal membrane Visceral pleura )- Esophagus ; Coronary ligament \¢ Inferior vena cava Sinusoids of liver Ductus venosus Falciform ligame EE Wall of umbilical cord Fic. 175.—Transverse section through the lungs and pleural cavities ofa 10mm. humanembryo. X 23. The bronchial anlages continue to branch in such a way that the stem bud is retained as the main bronchial stem (Fig. 174). That is, the branching is mono- podial, not dichotomous, lateral buds being given off from the stem bud proximal to its growing tip. Only in the later stages of development has dichotomous branching of the bronchi and the formation of two equal buds been described. Such buds, formed dichotomously, do not remain of equal size (Flint, Amer. Jour. Anat., vol. 6, 1906). The entodermal anlages of the lungs and trachea are developed in a median mass of mesenchyme dorsal and cranial to the peritoneal cavity. This tissue forms a broad mesentery termed the mediastinum (Fig. 175). The right and left 168 THE ENTODERMAL CANAL AND THE BODY CAVITIES stem buds of the lungs grow out laterad, carrying with them folds of the mesoderm. The branching of the bronchial buds takes place within this tissue which is cov- ered by the mesothelial lining of the body cavity. The terminal branches of the bronchi are lined with entodermal cells which flatten out and form the res- piratory epithelium of the adult lungs. The surrounding mesenchyme differen- tiates into the muscle, connective tissue, and cartilage plates of the lung, tracheal, and bronchial walls. Into it grow blood vessels and nerve fibers. When the pleural cavities are separated from the pericardial and peritoneal cavities, the mesothelium covering the lungs, with the connective tissue underlying it, becomes the visceral pleura. The corresponding layers lining the thoracic wall form the parietal pleura. These layers are derived respectively from the visceral (splanch- nic) and parietal (somatic) mesoderm of the embryo. ; } -+--Pulmonary artery / #4 »® ’&\ / ‘t Pulmonary vein \ 4 a be ‘ E> —., ae FE / \. es \ s / Fic. 176.—Ventral view of the lungs of a 10.5 mm. embryo showing the pulmonary arteries and veins (His in McMurrich). X 27. Ep., Apical bronchus; J, IZ, primary bronchi. In 11 mm. embryos the two pulmonary arteries, from the sixth pair of aortic arches, course lateral then dorsal to the stem bronchi (Fig. 176). The right pulmonary artery passes ventral to the apical bronchus of the right lung. The single pulmonary vein receives two branches from each lung, two larger veins from each lower lobe, two smaller veins from each upper lobe and the middle lobe of the right side. These four pulmonary branches course ventrad and drain into the pulmonary trunk. When this common stem is taken up into the wall of the left atrium, the four pulmonary veins open directly into the latter. According to Killiker, the air cells or alveoli of the lungs begin to form in the sixth month and their development is completed during pregnancy. Elastic tissue appears during the fourth month in the largest bronchi. The abundant connective tissue found between the bronchial branches in early fetal life becomes reduced in its relative amount as the alveoli of the lungs are developed. Before birth the lungs are relatively small, compact, and possess sharp margins. They lie in the dorsal portion of the pleural cavities. After birth they normally fill with air, ex- ESOPHAGUS, STOMACH AND INTESTINE 169 panding and completely filling the pleural cavities. Their margins become rounded and the compact fetal lung tissue, which resembles that of a gland in structure, becomes light and spongy, owing to the enormous increase in the size of the alveoli and blood vessels. Because of the greater amount of blood admitted to the lungs after birth, their weight is suddenly increased. In the most common anomaly involving the esophagus and trachea the former is divided transversely, the trachea opening into the lower portion of the esophagus, while the upper portion of the esophagus ends blindly. ESOPHAGUS, STOMACH AND INTESTINE Esophagus.—The esophagus in 4 to 5 mm. embryos is a short tube, flattened laterally, extending from the pharynx to the stomach. It grows rapidly in length and in 7.5 mm. embryos its diameter decreases both relatively and absolutely (Forssner). At this stage the esophageal epithelium is composed of two layers of columnar cells. In 20 mm. embryos, vacuoles appear in the epithelium and increase the size of the lumen which remains open throughout. In later stages the wall of the esophagus is folded, and ciliated epithelial cells appear at 44mm. (C R). The number of cell layers in the epi- thelium increases, until, at birth, they number nine or ten. Glands are developed as epi- thelial ingrowths. The circular muscle layer is indicated at 10 mm. but the longitudinal muscle fibers do not form a definite layer until 55 mm. (C R). (F. T. Lewis in Keibel and Mall, vol. 2.) These layers appear in similar time-sequence throughout the entire digestive tract. Stomach.—The stomach appears in embryos of 4 to 5 mm. as a laterally flattened, fusiform enlargement of the fore-gut caudal to the lung anlages (Figs. 177 and 178). Its epithelium is early thicker than that of the esophagus and is sur- rounded by a thick layer of splanchnic mesoderm. It is attached dorsally to the body wall by its mesentery, the greater omentum, and ventrally to the liver by the lesser omentum (Fig. 190 B). The dorsal border of the stomach both enlarges locally to form the fundus, and also grows more rapidly than the ventral wall throughout its extent, thus producing the convex greater curvature. The whole stomach becomes curved and its cranial end is displaced to the left by the en- larging liver (Fig. 168). This forms a ventral concavity, the lesser curvature, and produces the first flexure of the duodenum. The rapid growth of the gastric wall along its greater curvature also causes the stomach to rotate upon its long axis until its greater curvature, or primitive dorsal wall, lies to the left, its ventral wall, the lesser curvature, to the right (Fig. 201). The original right side is now dorsal, the left side ventral in position, and the caudal or pyloric end of the stomach is ventral and to the right of its cardiac or cephalic end. The whole organ extends obliquely across the peri-. 170 THE ENTODERMAL CANAL AND THE BODY CAVITIES toneal cavity from left to right (cf. Fig. 138). The change in position progresses rapidly and is already completed early in the second month (12 to 15 mm.). The rotation of the stomach explains the asymmetrical position of the vagus nerves of the adult organ, the left nerve supplying the ventral wall of the stomach, orig- inally the left wall, while the right vagus supplies the dorsal wall, originally the right. Gastric pits are indicated in 16 mm. embryos, and, at 100 mm. (C R), gland cells of the gastric glands are differentiated. These undoubtedly arise from the gastric epithelium (Lewis). The cardiac glands are developed early (91 mm. (C R) fetuses), and, according to Lewis, there is no ‘evidence in favor of Bensley’s conclusion that the cardiac glands are decadent . fundus glands.” Pharynx ons Root of tongue ao Thyreoid ~ SS XN Tip of tongue = SS \ —— Stomach x aes LS S MW Sy — Liver Yolk stalk Allantoic stalk Dorsal pancreas Cloaca Metane phros Mesonephric duct Fic. 178.—Reconstruction of a 5 mm. human embryo showing the entodermal canal and its derivatives (His in Kollmann). X 25. The attachment of the yolk stalk may persist in later stages (12 to 14 mm. embryos, according to Keibel, Elze, and Thyng). Also in 2 per cent. of adult intestines a pouch 3 to 9 cm. long is found about 80 cm. above the colic valve, where the yolk stalk was formerly attached. This pouch, the diverticulum of the ileum or Meckel’s diverticulum, is of clinical importance as it may cause intestinal strangulation in infants. At the stage shown in Fig. 179, the dorsal pancreatic anlage has been de- veloped from the duodenum, and, in the caudal limb of the intestinal loop, there 172 THE ENTODERMAL CANAL AND THE BODY CAVITIES is formed an enlargement, due to a ventral bulging of the gut wall, which marks the anlage of the cecum and the boundary line between the Jarge and small in- testine. The cecal anlage gives rise later both to the adult cecum and to a more distal appendage, the vermiform process, which lags in development and remains small. Succeeding changes in the intestine consist (1) in its torsion and coiling due to its rapid elongation, and (2) in the differentiation of its several regions. As Rathke’s pocket Hypophysis Thyreoid Notochord Pericardium Trachea Hepatic duct Esophagus Gall bladder Stomach Yolk stalk Liver Allantois Dorsal pancreas Ventral pancreas Cloacal membrane Caecum : : ms Urogenital sinws ° mae Peritoneal cavity: Tail gut Mesonephric duct Rectum Fic. 179.—Diagram, in median sagittal section, showing the digestive canal of a 9 mm. human embryo dapted from Mall). xX 9. the gut elongates in 9 to 10 mm. embryos, the intestinal loop rotates. Asa resuit, its caudal limb lies at the left and cranial to its cephalic limb (Fig. 179). At this stage the intestinal loop enters the ccelom of the umbilical cord, thus causing a temporary umbilical hernia. The small intestine soon lengthens rapidly and at 17 mm. (Fig. 180) forms loops within the umbilical cord. Six primary loops occur and these may be recognized in the arrangement of the adult intestine (Mall, Bull. Johns Hopkins Hosp., vol. 9, 1898). In embryos of 42 mm. the intestine has returned from the ESOPHAGUS, STOMACH AND INTESTINE 173 umbilical cord into the abdominal cavity through a rather small aperture; the coelom of the cord is soon after obliterated. In embryos between 10 and 30 mm., vacuoles appear in the wall of the duodenum and epithelial septa completely block the lumen. The remainder of the small intestine remains open, although vacuoles form in its epithelium. Vulli appear as rounded elevations of the epithelium at 23 mm. (Johnson). They begin to form at the cephalic end of the jejunum, and at 130 mm. (C R) they are found throughout the small intestine (Berry). Intestinal glands appear as ingrowths of the epithelium about the bases of the villi. They develop first in the duodenum at 91mm.(C R). The duodenal glands (of Brunner) are said to appear during the = Brain Hypophysis ZN \ Foramen cecum |_Root of tongue \=& , Tip of tongue = Whe iy Esophagus Thyreoid gland \ Se Trachea Pericardium Notochord Gall bladder D | Spinal cord Small intestine y Ail ives Caecum ~~ Stomach Dorsal pancreas a Ze s > Ventral pancreas Allantois NE Lp Colon Urogenital sinus i ER ecu een shonte ee Anal membrane Fic. 180.—Diagrammatic median sagittal section of a 17 mm. human embryo, showing the digestive canal (modified after Mall). Xx 5. fourth month (Brand). In embryos of 10 to 12.5 mm. the circular muscle layer of the intes- tine first forms. The longitudinal muscle layer is not distinct until 75 mm. (C R). The impervious duodenum of the embryo may persist as a congenital anomaly, and the persistence of the yolk stalk, as Meckel’s diverticulum, has already been mentioned (p. 171). The large intestine, as seen in 9 mm. embryos (Fig. 179), forms a tube extend- ing from the cecum to the cloaca. It does not lengthen so rapidly as the small intestine, and, when the intestine is withdrawn from the umbilical cord (at 42 mm. C R), its cranial or cacal end lies on the right side and dorsal to the small intestine (Fig. 181). It extends transversely to the left side as the transverse 174 THE ENTODERMAL CANAL AND THE BODY CAVITIES colon, then bending abruptly caudad as the descending colon, returns by its iliac flecure to the median plane and forms the rectum. Fic. 181.—Three successive stages showing the development of the digestive tube and the mesen- teries in the human fetus (Tourneux in Heisler): r, Stomach; 2, duodenum; 3, small intestine; 4, colon; 5, yolk stalk; 6, caecum; 7, great omentum; 8, mesoduodenum; 9, mesentery; ro, mesocolon. The arrow points to the orifice of the omental bursa. The ventral mesentery is not shown. The cecum (Fig. 182) may be distinguished from the vermiform process at 65 mm. (C R) (Tarenetzky). The caecum and vermiform process make a U- Ascending _{ 2M ; mesocolon 1, Ascending __\ colon Cecum—p a tiagcse Processus _- 48 ¢ t Processus vermiformis = vermiformis Fic. 182.—The cecum of a human fetus of 50 mm. (Kollmann): A, from the ventral side; B, from the dorsal side. shaped bend with the colon at 42 mm. (C R), and this flexure gives rise to the colic valve (Toldt). In stages between 100 and 200 mm. (C R) the lengthening of the THE LIVER 175 colon causes the caecum and cephalic end of the colon to descend toward the pelvis (Fig. 181). The ascending colon is thus formed and the vermiform appendix takes the position which it occupies in the adult. The circular muscle layer of the large intestine appears first at 23 mm., the longitudinal layer at 75 mm. (CR). In 55 mm. (C R) fetuses villi are present. The development of the entire digestive tract has been described by Johnson (Amer. Jour. Anat., vols. 10, 1910; 14, 1913; 16, 1914). Glandular secretions and desquamated entodermal cells, together with swallowed amniotic fluid, containing lanugo hairs and vernix caseosa, collect in the fetal intestine. This mass, yellow to brown in color, is known as meconium. At birth the intestine and its contents are perfectly sterile. .THE LIVER In embryos of 2.5 mm. the liver anlage is present as a median ventral out- _growth from the entoderm of the fore-gut just cranial to the yolk stalk (Fig. 167 B). Its thick walls enclose a cavity which is continuous with that of the gut. This hepatic diverticulum becomes embedded at once in a mass of splanchnic mesoderm, the septum transversum. Cranially, the septum will contribute later to the forma- tion of the diaphragm; caudally, in the region of the liver anlage, it be- comes the ventral mesentery (Fig. 189). Thus, from the first the liver is in close relation to the septum transversum and later when the septum becomes a part of the dia- phragm the liver remains attached to it. In embryos 4 to 5 mm. long, solid cords of cells proliferate from Fic. 183—Model of the liver anlage of a4 mm. the ventral and cranial portion of human embryo (Bremer). X 160. Jn., Intestine; Pa., pancreas; V., veins in contact with liver tra- becule. the hepatic diverticulum (Fig. 86). These cords anastomose and form a crescentic mass with wings extending dorsad lateral to the gut (Fig. 177). This mass, a network of solid trabecule, is the glandular portion of the liver. The primitive, hollow diverticulum later differentiates into the gall bladder and the large biliary ducts. 176 THE ENTODERMAL CANAL AND THE BODY CAVITIES Referring to Fig. 88, it will be seen that the liver anlage lies between the vitelline veins and is in close proximity to them laterally. The veins send anas- tomosing branches into the ventral mesentery. The trabecule of the expanding liver grow between and about these venous plexuses, and the plexuses in turn Fic. 184.—The trabecule and sinusoids of the liver in section (after Minot). X 300. Tr., Trabecule of liver cells; S7., sinusoids. make their way between and around the liver cords (Fig. 183). The vitelline veins on their way to the heart are thus surrounded by the liver and largely sub- divided into a network of vessels termed sinusoids. The endothelium of the sinu- soids is closely applied to the cords of liver cells, which, in the early stages, contain A B Stomach Hepatic duct Hepatic duct Ductus choledochus a Ventral pancreas Gall bladder Cystic duct Ductus choledochus Duct of dorsal’ ky Ae pancreas pancreas f Head of dorsal pancreas Ventral pancreas’ £ Fic. 185.—Reconstructions showing the development of the hepatic diverticulum and pancreatic anlages. A, 7.5 mm. human embryo (after Thyng), X 50; B, 10 mm. human embryo, X 33. no bile capillaries (Fig. 184). The transformation of the vitelline veins into the portal vein and the relations of the umbilical veins to the liver will be treated in Chapter IX. The glandular portion of the liver grows rapidly, and, in embryos of 7 to 8 mm., is connected with the primitive hepatic diverticulum only by a single cord THE LIVER £77 of cells, the hepatic duct (Fig. 185 A). That portion of the hepatic diverticulum distal to the hepatic duct is now differentiated into the terminal, solid gall bladder and its cystic duct. Its proximal portion forms the ductus choledochus. In embryos of 10 mm. (Fig. 185 B) the gall bladder and ducts have become longer and more slender. The hepatic duct receives a right and left branch from the corresponding lobes of the liver. The gall bladder is without a lumen up to the 15 mm. stage. Later its cavity appears, surrounded by a wall of high columnar epithelium. The glandular portion of the liver develops fast and is largest relative to the size of the body at 31 mm. (Jackson). In certain regions the liver tissue under- goes degeneration, and especially is this true in the peripheral portion of the left d d a Fic. 186.—Diagrams of three successive stages of the portal and hepatic veins in a growing liver: a, Hepatic side; d, portal side; b and c, successive stages of the hepatic vein; e and f, successive stages of the portal vein (Mall). lobe. In general, the external lobes of the liver are moulded under the influence of the fetal vitelline and umbilical trunks. The development of the ligaments of the liver is described on p. 192. During the development of the liver the endothelial cells of the sinusoids become stellate in outline, and thus form an incomplete layer. From the second month of fetal life to some time after birth, blood cells are actively developed between the hepatic cells and the endo- thelium of the sinusoids. Lumina bounded by five or six cells may be observed in some of the liver trabecule of 10 mm. embryos (Lewis). At 22 mm. hollow periportal ducts develop, spreading inward from the hepatic duct along the larger branches of the portal vein. In 44 mm. (C R) fetuses, bile capillaries with cuticular borders are present, most numerous near the periportal ducts with which some of them connect. At birth, or shortly after, the number of liver cells surrounding a bile capillary is reduced to two, three, or four. Secretion of the bile commences at about the end of the third fetal month. I2 178 THE ENTODERMAL CANAL AND THE BODY CAVITIES The lobules, or vascular units of the liver, are formed, according to Mall, by the peculiar and regular manner in which the veins of the liver branch. The primary branches of the portal vein extend along the periphery of each primitive lobule, parallel to similar branches of the hepatic veins which drain the blood from the center of each lobule (Fig. 186). -As development proceeds, each primary branch becomes a stem, giving off on either side second- ary branches which bear the same relation to each other and to new lobules as did the primary branches to the first lobule. This process is repeated until thousands of liver lobules are developed. ¥ Until the 20 mm. stage the portal vein alone supplies the liver. The hepatic artery, from the cceliac axis, comes into relation first with the hepatic duct and gall bladder. Later, it grows into the connective tissue about the larger bile ducts and branches of the portal vein, and also supplies the capsule of the liver. Anomalies.—A common anomaly of the liver consists in its subdivision into multi- ple lobes. Absence or duplication of the gall bladder and of the ducts may occur. In some animals (horse, elephant) the gall bladder is normally absent. THE PANCREAS Two pancreatic anlages are developed almost simultaneously in embryos of 3 to 4mm. The dorsal pancreas arises as a hollow outpocketing of the dorsal duodenal wall just cranial to the hepatic diverticulum (Fig. 177). At 7.5 mm. it is B Ventral pancreas Pancreatic duct Bile duct Bile duct Pancreatic duct Ventral pancreas Fic. 187.—Two stages showing the development of the human pancreas: A, Embryo of 8 mm.; B, embryo of about 20 mm. (after Kollman). separated from the duodenum by a slight constriction and extends into the dorsal mesentery (Fig. 185 A). The ventral pancreas develops in the inferior angle be- tween the hepatic diverticulum and the gut (Lewis) and its wall is at first continu- ous with both. With the elongation of the ductus choledochus its origin is trans- ferred to this portion of the diverticulum. Of the two pancreatic anlages, the dorsal grows more rapidly and in 10 mm. embryos forms an elongated structure with a central duct and irregular nodules upon its surface (Fig. 185 B). The ventral pancreas is smaller and develops a short slender duct which opens into the ductus choledochus. When the stomach and duodenum rotate the pancreatic ducts shift their positions as well. At the BODY CAVITIES, DIAPHRAGM AND MESENTERIES 179 same time, growth and bending of the bile duct to the right bring the ventral pancreas into close proximity with the dorsal pancreas (Figs. 185 and 187). In embryos of 20 mm. the tubules of the dorsal and ventral pancreatic an- lages interlock (Fig. 187 B). Eventually, anastomosis takes place between the two ducts, and the duct of the ventral pancreas plus the distal segment of the dorsal duct persist as the functional pancreatic duct of the adult. The proximal portion of the dorsal pancreatic duct forms the accessory duct, which remains pervious, but becomes a tributary of the adult pancreatic duct. The ventral pancreas forms part of the head and uncinate process of the adult gland. The dorsal pancreas takes part in forming the head and uncinate process and com- prises the whole of the body and tail. ‘The ventral pancreas may arise directly from the intestinal wall (Bremer; Keibel and Elze), and paired ventral anlages also occur (Debeyre; Helly; Kollmann). Accessory pan- creases are not uncommon. Both the dorsal and ventral ducts persist in the horse and dog; in the sheep and man the ventral duct becomes of chief importance; in the pig and ox the dorsal duct. In 10 mm. embryos the portal vein separates the two pancreatic anlages and later they partially surround the vein. The alveoli of the gland are developed from the ducts as darkly staining cellular buds in fetuses of 40 to 55 mm.(C R). The islands characteristic of the pancreas also bud from the ducts (and alveoli, Mironescu, 1910) and appear first in the tail at 55 mm. (C R). Owing to the shift in the position of the stomach and duodenum during development, the pancreas takes up a transverse position, its tail extending to the left. To its ventral sur- face is attached the transverse mesocolon. BODY CAVITIES, DIAPHRAGM AND MESENTERIES The Primitive Ceelom and Mesenteries.—In the Peters embryo the primary mesoderm has already split to form the extra-embryonic ccelom (Fig. 74 C). When the intra-embryonic mesoderm differentiates, numerous clefts appear on either side between the somatic and splanchnic layers of mesoderm. ‘These clefts coalesce in the cardiac region and form two elongated pericardial cavities lateral to the paired tubular heart. Similarly, right and left pleuro-peritoneal cavities are formed between the mesoderm layers caudal to the heart. The paired peri- cardial cavities extend toward the midline cranial to the heart and communicate with each other (Fig. 188). Laterally they are not continuous with the extra- embryonic coelom, for the head of the embryo separates early from the underlying blastoderm. The pericardial cavities also are prolonged caudally until they open into the pleuro-peritoneal cavities. These in turn communicate laterally with the extra-embryonic cclom. In an embryo of 2 mm. the ccelom thus consists of a U-shaped pericardial cavity, the right and left limbs of which are continued 180 THE ENTODERMAL CANAL AND THE BODY CAVITIES caudally into the paired pleuro-peritoneal cavities; these extend out into the extra- embryonic ccelom. When the head fold and fore-gut of the embryo are developed, the layers of splanchnic mesoderm containing the heart tubes are folded together ventral te the fore-gut and form the ventral mesentery between the gut and the ventral body wall (Fig. 190). Owing to the position of the yolk sac, the caudal extent of the ventral mesentery is limited. At the level of each side, where the vitello-umbilical trunk (Fig. 88) courses to the heart, the splanchnic mesoderm and the somatic mesoderm are united (cf. Fig. 110). Thus is formed the septum transversum, which incompletely partitions the ccelom [pn ee a ° . A Pericardial cavity into a cranial and caudal portion (Fig. 189). Cranial to the septum, the heart is suspended in the ventral mesentery Surface of fore-gut which forms the dorsal and ventral meso- cardia (Fig. 190 A). Into the ventral Pleuro-peritoneal canal oe mesentery caudal to the septum grows Entoderm of gut 3 . 7 the liver. This portion of the ventral Peritoneal cavity mesentery gives rise dorsally to the lesser XM Extra-embryonic celom Vit—Wall of yolk sac Fic. 188.—Diagrammatic model of the ; fore-gut and ccelom in an early humanem- versum, It forms the ligaments of the bryo, viewed from above and behind (modi- fied after Robinson). omentum of the stomach, and, where it fails to separate from the septum trans- liver. Ventrally it persists as the falciform ligament (Fig. 190 B). Dorsal to the gut, the splanchnic mesoderm of each side is folded together in the median sagittal plane to constitute the dorsal mesentery which extends to the caudal end of the digestive canal (Figs. 189 and 190 C). This suspends the stomach and intestine from the dorsal body wall and is divided into the dorsal mesogastrium or greater omentum of the stomach, the mesoduodenum, the mesen- tery proper of the small intestine, the mesocolon, and the mesorectum. The covering layers of the viscera, of the mesenteries, and of the body wall are continuous with each other and consist of a mesothelium overlying connective tissue. The parietal lining is derived from the somatic layer of mesoderm and the visceral covering from the splanchnic layer. The primitive celom lies in the horizontal plane, as in Fig. 188. Coincident with the caudal regression of the septum transversum, the pericardial cavity is bent ventrad and enlarged (Fig. 191). The ventral mesocardium attaching the heart to the ventral body wall disappears and the right and left limbs of the BODY CAVITIES, DIAPHRAGM AND MESENTERIES 181 U-shaped cavity become confluent ventral to the heart. The result is a single, large pericardial chamber, the long axis of which now lies in a dorso-ventral plane Esophagus Spinal cord Dorsal mesocar- Pericardial cavity ‘ dium Ventricle of heart phe Ventral mesocardium Septum bransversum Liver __ Ventral mesentery (falciform ligament) coe Stomach B Ventral mesentery (lesser omentum) Dorsal mesogastrium Dorsal pancreas > Mesorectum Fic. 189.—Diagram showing the primitive mesenteries of an early human embryo in median sagittal sec- tion. The broken lines (A, B, and C) indicate the level of sections A, B, and C in Fig. 190. Neural tube Notochord Dorsal mesentery Fore-gut Aorta Notochord: Postcar- dinal vein Dorsal mesentery. Pericardial Peritoneal celom hie Ventral Fake mesocardium a. ciform ligament A B Cc Fic. 190.—Diagrammatic transverse sections. A, Through the heart and pericardial cavities of an early human embryo; B, through the fore-gut and liver; C, through the intestine and peritoneal cavity. nearly at right angles to the plane of the pleuro-peritoneal cavities, and con- nected with them dorsally by the right and left pleuro-peritoneal canals. The division of the primitive ccelom into separate cavities is accomplished by 182 THE ENTODERMAL CANAL AND THE BODY CAVITIES , the development of three membranes which join in a <-shaped fashion (Figs. 194 and 195): (1) the septum transversum, which separates incompletely the peri- cardial and pleural cavities from the peritoneal cavities; (2) the paired pleuro- pericardial membranes, which complete the division between pericardial and pleural cavities; (3) the paired pleuro-peritoneal membranes, which complete the partition between each pleural cavity, containing the lung, and the peritoneal cavity, which contains the abdominal viscera. The Septum Transversum.—The vitelline veins, on their way to the heart, course in the splanchnic mesoderm lateral to the fore-gut. In embryos of 2 to 3 -Bulbus cordis . . . Dorsal mesocardium Pericardial cavity Sinus venosus Somatopleure Lateral mesocardium ari pil - Septum transversum Common cardinal vein Umbilical vein Vitelline vein overlying stomach Pleuro-peritoneal canal Volk stalk 1 Vb Peritoneal cavity Fic. 191.—Reconstruction cut at the left of the median sagittal plane of a 3 mm. human embryo, showing the body cavities and septum transversum (Kollmann). mm. these large vessels bulge into the ccelom until they meet and fuse with the somatic mesoderm (Figs. 88 and 110). Thus there is formed caudal to the heart a transverse partition filling the space between the sinus venosus of the heart, the gut, and the ventral body wall, and separating the pericardial and peri- toneal cavities from each other ventral to the gut. This mesodermal partition was termed by His the septum transversum. In Fig. 191 it comprises both a cranial portion (designated ‘septum transversum”), which is the anlage of a large part of the diaphragm, and a caudal portion, the ventral mesentery, into which the liver grows. At first the septum transversum does not extend dorsal to the gut, but leaves BODY CAVITIES, DIAPHRAGM AND MESENTERIES 183 on either side a plewro-peritoneal canal through which the pericardial and pleuro- peritoneal cavities communicate (Fig. 191). In embryos of 4 to 5 mm. the lungs develop in the median walls of these canals and bulge laterally into them. Thus the canals become the pleural cavities and will be so termed hereafter. On account of the more rapid growth of the embryo, there is an ap- parent constriction at the yolk stalk, and, with the development of the um- bilical cord, the peritoneal cavity is finally separated from the extra-em- bryonic ccelom. Dorsally, the pleural and peritoneal cavities are permanently partitioned lengthwise by the dorsal mesentery. The septum transversum in 2 mm. embryos occupies a transverse position in the middle cervical region (Fig. 192, 2). According to Mall, it migrates caudally, its ventral position at first moving more rapidly so that its position be- comes obligue. In 5 mm. embryos (Fig. 192, 5) it is opposite the fifth cervical segment, at which level it receives the Fic. 192—Diagram showing the change in position of the septum transversum in stages phrenic nerve. In stages later than 7 from 2 to 24 mm. (modified after Mall). The septum is indicated at different stages by the numerals to the left, the numbers correspond- at 24 mm. it is opposite the first lum- ing to the length of the embryo at each stage. bare gment. During this second period The letters and numbers at the right represent the segments of the occipital, cervical, thoracic of migration its dorsal attachment travels and Jumbar regions. mm. the septum migrates caudad, until faster than its ventral portion. ‘There- fore, it rotates to a position nearly at right angels to its plane in 7 mm. embryos and its original dorsal surface becomes its ventral surface. The Pleuro-pericardial and Pleuro-peritoneal Membranes.—The common cardinal veins (ducts of Cuvier) on their way to the heart curve around the pleural cavities laterally in the somatic body wall (Figs. 191 and 193). In embryos of 7 mm. each vein, with the overlying mesoderm, forms a ridge which projects from the body wall mesially into the pleural canals. This ridge, the pulmonary ridge of Mall, is the anlage of both the pleuro-pericardial and pleuro-peritoneal ¢ 184 THE ENTODERMAL CANAL AND THE BODY CAVITIES membranes. Later it broadens and thickens cranio-caudally (Fig. 193), forming a triangular structure whose apex is continuous with the septum transversum (Fig. 194). Its cranial side forms the pleuro-pericardial membrane and in 9 to 10 mm. embryos reduces the opening between the pleural and pericardial cavities to a mere slit. Its caudal side becomes the pleuro-peritoneal membrane, which eventually separates dorsally the pleural from the peritoneal cavity (Fig. 195). Pericardial cavity Common cardinal vein Pleuro-pericardial membrane Pleuro- peritoneal Lung bud | membrane Liver Vein to limb bud Stomach Mesonephros Fic. 193.—Reconstruction of a 7 mm. human embryo showing from the left side the pleuro-pericardial membrane, the pleuro-peritoneal membrane and the septum transversum (after Mall). X 20. The phrenic nerve courses in the pleuro-pericardial membrane. Arrow passes from pericardial to peritoneal cavity through the pleuro-pericardial canal. The two sets of membranes at first lie nearly in the sagittal plane and a portion of the lung is caudal to the pleuro-peritoneal membranes (Fig. 193). Between the stages of 7 and 11 mm. the dorsal attachment of the septum transversum is carried caudally more rapidly than its ventral portion and its primary ventral surface becomes its dorsal side (Figs. 192 to 194). The pleuro-peritoneal mem- brane is carried caudad with the septum transversum until the lung lies in the angle between the pleuro-peritoneal and pleuro-pericardial membranes and is BODY CAVITIES, DIAPHRAGM AND MESENTERIES 185 included within the spherical triangle which has been described above (Fig. 194). During this rotation the dorsal end of the pleuro-pericardial membrane lags behind and so takes up a position in a coronal plane nearly at right angles to the septum transversum (Figs. 194 and 195). In 11 mm. embryos the pleuro -pericardia] membranes have fused completely on each side with the median walls of the pleural canals and thus separate the pericardium from the paired pleural ca vities. Pleuro-pericardial membrane Phrenic nerve Pericardial cavity Septum transversum peritoneal membrane Mesonephros Stomach Frc. 194.—Reconstruction of an 11 mm. human embryo to show the same structures as in Fig. 193 (after Mall). X 14. By way of the pleuro-pericardial membranes the phrenic nerves course to the septum transversum (Fig. 194). The pleuro-peritoneal membranes are continuous dorsally and caudally with the mesonephric folds; ventrally and caudally they fuse later with the dorsal pillars of the diaphragm or coronary appendages of the liver (Lewis) (Fig. 196). Between the free margins of the membranes and the mesentery a temporary open- ing is left on each side, through which the pleural and peritoneal cavities com- municate (Figs. 194 and 200). 186 THE ENTODERMAL CANAL AND THE BODY CAVITIES Esophagus Mesoderm of left lung bud Pleural cavily Pericardial cavity Bae aie Be Lary Ne: Pleuro-perttoneal Pleuro-pericardial ier be ‘ membrane membrane — Phrenic nerve Wall of heart Septum transversum Liver Falciform ligament Fic. 195.—Transverse section through a 10 mm. human embryo showing the pleuro-pericardial mem- brane separating the pericardium from the pleural cavities. X 33. Esophagus _ : Pleural cavity Right lung a: Pleuro-peritoneat membrane Coronary appendage of liver Phrenic nerve in septum Vena cava inferior lransversum Fic. 196.—Transverse section through a 10 mm. human embryo showing the pleuro-peritoneal mem- branes. X 16. Owing to the caudal migration of the septum transversum and the growth of the lungs and liver, the pleuro-peritoneal membrane, at first lying in a nearly BODY CAVITIES, DIAPHRAGM AND MESENTERIES 187 sagittal plane (Fig. 193), is shifted to a horizontal position (Fig. 194), and gradu- ally its free margin unites with the dorsal pillars of the diaphragm and with the dorsal mesentery. The opening between the pleural and peritoneal cavities is thus narrowed and finally closed in embryos of 19 to 20 mm. A B Esophagus Common cardinal vein Pleuro-pericardial canal Pericardial cavity Septum transversum Pleuro-peritoneal membrane Heart — Pericardial membrane Fic. 197.—Diagrams showing the development of the lungs and the formation of the pericardial mem- brane (modified after Robinson). A, Coronal section; B, transverse section. The Diaphragm and Pericardial Membrane.—The lungs grow and expand not only cranially and caudally but also laterally and ventrally (Fig. 197). Room is made for them by the obliteration of the very loose, spongy mesenchyme of the adjacent body wall (Fig. 196). As the lungs burrow laterally and ventrally Fic. 198.—Diagram showing the origin of the diaphragm (after Broman): z, Septum transver- sum; 2, 3, derivatives of mesentery; 4, 4, derivatives of pleuro-peritoneal membrane; 5, 5, parts derived from the body walls; A, aorta; Oe, esophagus; VC, inferior vena cava. into the body wall around the pericardial cavity, the pleuro-pericardial mem- branes enlarge at the expense of this tissue and more and more the heart comes to lie in a mesial position between the lungs (Fig. 197 B). The pleural cavities thus increase rapidly in size. 188 THE ENTODERMAL CANAL AND THE BODY CAVITIES At the same time the liver grows enormously, and on either side a portion of the body wall is taken up into the septum transversum and pleuro-peritoneal membranes. The diaphragm, according to Broman, is thus derived from four sources (Fig. 198): (1) its ventral pericardial portion from the septum trans- versum; its lateral portions from (2) the pleuro-peritoneal membranes plus (3) derivatives from the body wall; lastly, a median dorsal portion is formed from (4) the dorsal mesentery. In addition to these, the striated muscle of the dia- phragm, according to Bardeen, takes its origin from a pair of premuscle masses which in 9 mm. embryos lie one on each side opposite the fifth cervical segment. Right umbilical vein Left umbilical vein Ventral mesentery Ectoderm of body wall Left lobe of liver Right lobe of liver Ventral mesentery . Duodenum Lesser peritoneal sac Plica ven@ cave Dorsal aorla Neural tube Fic. 199.—Diagrammatic model of an embryo of 7 to 9 mm. showing the position of the lesser peri- toneal sac. The embryo is represented as sectioned transversely, caudal to the liver, so that one looks at the caudal surface of the section and of the liver, and cranially into the body cavities. This is the level at which the phrenic nerve enters the septum transversum. The exact origin of these muscle masses is in doubt, but they probably repre- sent portions of the cervical myotomes of this region. The muscle masses migrate caudally with the septum transversum and develop chiefly in the dorsal portion of the diaphragm (Bardeen, Johns Hopkins Hospital Report, vol. 9, 1900). Keith (Jour. Anat. and Physiol., vol. 39, 1905) derives the muscle of the diaphragm also from the rectus and transversalis muscles of the abdominal wall. The cavities of the mesodermic segments are regarded as portions of the ccelom, but in man they disappear early. The development of the vaginal sacs which grow out from the inguinal region of the peritoneal cavity into the scrotum will be described in Chapter VIII. BODY CAVITIES, DIAPHRAGM AND MESENTERIES 189 The Omental Bursa or Lesser Peritoneal Sac.—According to Broman, the omental bursa is represented in 3 mm. embryos by a peritoneal pocket which extends cranially into the dorsal mesentery to the right of the esophagus. A similar pocket present on the left side has disappeared in 4 mm. embryos. Lateral to the opening of the primitive lesser peritoneal sac, a lip-like fold of the mesentery ay Body wall Falciform ligament Coronary attachment of liver to diaphragm Inferior vena cava Sup. recess of lesser peritoneal sac Pleuro-peritoneal foramen Pleuro-peritoneal Pleuro-peritoneal membrane membrane Lesser omentum Inferior vena cava Plica vene cave Mesonephric fold Genital fold Lesser peritoneal sac Aorta Fic. 200.—A diagrammatic ventral view of the middle third of a human embryo 12 to 15 mm. long. The figure shows the caudal surface of a section through the stomach and spleen, a ventral view of the stomach, the liver having been cut away to leave the sectioned edges of the lesser omentum and plica ven cave, and the caudal surface of the septum transversum and pleuro-peritoneal membrane. Upon the surface of the septum is indicated diagrammatically the attachment of the liver. (Based on figures of Mall and F. T. Lewis and model by H. C. Tracy.) is continued caudally along the dorsal body wall into the mesonephric fold as the plica vene cave, in which the inferior vena cava later develops (Fig. 199). The liver, it will be remembered, grows out into the ventral mesentery from the fore- gut, and, expanding laterally and ventrally, takes the form of a crescent. Its right lobe comes into relation with the plica vene cave, and, growing rapidly caudad, forms with the plica a partition between the lesser sac and the peritoneal Igo THE ENTODERMAL CANAL AND THE BODY CAVITIES cavity. Thus the cavity of the lesser peritoneal sac is extended caudally from a point opposite the bifurcation of the lungs to the level of the pyloric end of the stomach. In 5 to 10 mm. embryos it is crescent-shaped in cross-section (cf. Fig. 111) and is bounded mesially by the greater omentum (dorsal mesentery) and the right wall of the stomach, laterally by the liver and plica vene cave, and ven- trally by the lesser omentum (ventral mesentery). It communicates to the right with the peritoneal cavity through an opening between the liver ventrally and the plica venz cave dorsally (Fig. 201). This opening is the epiploic fora- Suprarenal gland OD Mesone phros F Greater omentum Liver Lesser peritoneal sac Stomach Duodenum Vitelline vei - Intestinal loop— Left umbilical vein Fic. 201.—An obliquely transverse section through a 10 mm. human embryo at the level of the epiploic foramen (of Winslow). X 33. men (of Winslow). When the dorsal wall of the stomach rotates to the left the greater omentum is carried with it to the left of its dorsal attachment. Its tissue grows actively to the left and caudally and gives the omentum an appearance of being folded on itself between the stomach and the dorsal body wall (Fig. 200). The cavity of the lesser peritoneal sac is carried out between the folds of the greater omentum as the inferior recess of the omental bursa. From the cranial end of the sac there is constricted off a small closed cavity which is frequently persistent in the adult. This is the bursa infracardiaca and may be regarded as a third pleural cavity. It lies at the right of the esophagus in the mediastinum. BODY CAVITIES, DIAPHRAGM AND MESENTERIES Ig! When the stomach changes its position and form so that its mid-ventral line becomes the lesser curvature and lies to the right, the position of the lesser omentum is also shifted. From its primitive location in a median sagittal plane with its free edge directed caudally, it is rotated through 90° until it lies in a cor- onal plane with its free margin facing to the right (Fig. 194). The epiploic fora- men now forms a slit-like opening leading from the peritoneal cavity into the ves- tibule of the omental bursa. The foramen is bounded ventrally by the edge of the lesser omentum, dorsally by the inferior vena cava, cranially by the caudate process of the liver, and caudally by the wall of the duodenum. During fetal life the greater omentum grows rapidly to the left and caudad in the form of a sac, flattened dorso-ventrally. It overlies the intestines ven- Fic. 202.—Diagrams showing the development of the mesenteries (Hertwig). A illustrates the beginning of the great omentum and its independence of the transverse mesocolon; in B the two come into contact; in C they have fused; A, stomach; B, transverse colon; C, small intestine; D, duodenum; E, pancreas; F, greater omentum; G, greater sac; H, omental bursa. trally and contains the inferior recess of the omental bursa (Fig. 202). The dor- sal wall of the sac during the fourth month usually fuses with the transverse colon where it overlies the latter (Fig. 202 B). Caudal to this attachment the walls of the greater omentum may be fused and its cavity is then obliterated. The inferior recess of the omental bursa thus may be limited in the adult chiefly to a space between the stomach and the dorsal fold of the greater omentum, which latter is largely fused to the peritoneum of the dorsal body wall. The spleen develops in the cranial portion of the greater omentum and that portion of the omentum which extends between the stomach and spleen is known as the gastro- lienic ligament (Fig. 200). The dorsal wall of the omentum between the spleen and kidney is the /ieno-renal ligament. Further Differentiation of the Mesenteries.— Ligaments of the Liver —We 192 THE ENTODERMAL CANAL AND THE BODY CAVITIES have seen (p. 179) that the cranial portion of the ventral mesentery forms the mesocardium of the heart. In the ventral mesentery caudal to the septum trans- versum the liver develops. From the first, it is enveloped in folds of the splanch- nic mesoderm which give rise to its capsule and ligaments as the liver increases in size (Fig. 190 B). Wherever the liver is unattached, the mesodermal layers of the ventral mesentery form its capsule (of Glisson), a fibrous layer covered by mesothelium, continuous with that of the peritoneum (Fig. 190 B). Along its mid-dorsal and mid-ventral line the liver remains attached to the ventral mesentery. The dorsal attachment between the liver, stomach, and duodenum is the lesser omentum. This in the adult is differentiated into the duodeno-hepatic and gastro-hepatic ligaments. The attachment of the liver to the ventral body wall extends caudally to the umbilicus and forms the falciform ligament. In its early development the liver abuts upon the septum transversum, and in 4 to 5 mm. embryos is attached to it along its cephalic and ventral surfaces. Soon dorsal prolongations of the lateral liver lobes, the coronary appendages, come into relation with the septum dorsally and laterally. The attachment of the liver to the septum transversum now has the form of a crescent, the dorsal horns of which are the coronary appendages (Fig. 200). This attachment be- comes the coronary ligament of the adult liver. The dorso-ventral extent of the coronary ligament is reduced during development and its lateral extensions upon the diaphragm give rise to the triangular ligaments of each side. The right lobe of the liver, as we have seen, comes into relation along its dorsal surface with the plica vene cave in 9 mm. embryos (Figs. 199 and 200). This attachment extends the coronary ligament caudally on the right side and makes possible the connection between the veins of the liver and mesonephros which contributes to the formation of the inferior vena cava. The portion of the liver included between the plica venz cave and the lesser omentum is the caudate lobe (of Spigelius). In a fetus of five months the triangular ligaments mark the position of the former lateral coronary appendages. The umbilical vein courses in a deep groove along the ventral surface of the liver, and, with the portal vein and gall bladder, bounds the guadrate lobe. Changes in the Dorsal Mesentery.—That part of the digestive canal which lies within the peritoneal cavity is suspended by the dorsal mesentery, which at first forms a simple attachment extending in the median sagittal plane between body wall and primitive gut. That portion of it connected with the stomach forms the greater omentum, the differentiation of which has been described (p. 191). BODY CAVITIES, DIAPHRAGM AND MESENTERIES 193 The mesentery of the intestine is carried out into the umbilical cord between the limbs of the intestinal loop. When the intestine elongates and its loop rotates, the caecal end of the large intestine comes to lie cranially and to the left, the small intestine caudally and to the right, the future duodenum and colon crossing in close proximity to each other (Fig. 179). On the return of the intestinal loop into the abdomen from the umbilical cord, the cecal end of the colon lies to the right and the transverse colon crosses the duodenum ventrally and cranially (Fig. 203 A). The primary loops of the small intestine lie caudal and to the left of the ascending colon (Fig. 203 B). There has thus been a torsion of the mesen- tery about the origin of the superior mesenteric artery as an axis. From this focal Lesser omentum Dorsal mesogastrium omentum Transverse mesocolon Iliac mesocolon Fic. 203.—Diagrams showing the development of the mesenteries in ventral view (modified after Tourneux). * Cut edge of greater omentum; a, area of ascending mesocolon fused to dorsal body wall; b, area of descending mesocolon fused to dorsal body wall. Arrow in omental bursa. point the mesentery of the small intestine and colon spreads out fan-like. The mesoduodenum is pressed against the dorsal body wall, fuses with its peritoneal layer, and is obliterated (Fig. 202). Since the transverse colon lies ventral to the duodenum it cannot come into apposition with the body wall; where its mesentery crosses the duodenum it fuses at its base with the surface of the latter and of the pancreas. Its fixed position now being transverse instead of sagittal, the mesen- tery is known as the transverse mesocolon. The mesentery of the ascending colon is flattened against the dorsal body wall on the right and fuses with the peritoneum (Fig. 203). Similarly, the descending mesocolon is applied to the body wall of the left side. There are thus left free: (1) the transverse mesocolon; (2) the mesen- 13 194 THE ENTODERMAIL CANAL AND THE BODY CAVITIES tery proper of the jejunum and ileum, with numerous folds corresponding to the loops of the intestine; (3) the iliac mesocolon; (4) the mesorectum, which retains its primitive relations. Anomalies of the diaphragm and mesenteries are not uncommon. The persistence of a dorsal opening in the diaphragm, more commonly on the left side, finds its explanation in the imperfect development of the pleuro-peritoneal membrane. Such a defect may lead to diaphragmatic hernia, the abdominal viscera projecting to a greater or less extent into the pleural cavity. The mesenteries also may show malformations, due to the persistence of the simpler embryonic conditions, usually correlated with the defective development of the intestinal canal. In about 30 per cent. of cases the ascending and descending mesocolon is more or less free, having failed to fuse with the dorsal peritoneum. The primary sheets of the greater omentum may also fail to unite, so that the inferior recess extends to the caudal end of the greater omentum. A striking anomaly is situs viscerum inversus, in which the various visceral organs are transposed right for left and left for right as in a mirror image. An independent transposi- tion of the thoracic or abdominal viscera alone may occur. The larger left great venous trunks are thought to be chiefly responsible for the usual positions of the viscera. CHAPTER VIII THE DEVELOPMENT OF THE UROGENITAL SYSTEM THE excretory and reproductive systems are intimately associated in develop- ment. Both arise from the mesoderm of the intermediate cell mass (nephrotome), which unites the primitive segments with the lateral somatic and splanchnic mesoderm (p. 52; Fig. 205). Vertebrates possess excretory organs of three distinct types. The pronephros is the functional kidney of amphioxus and certain lampreys, but appears only in immature fishes and amphibians, being replaced by the mesonephros. The em- bryos of amniotes (reptiles, birds, and mammals) possess first a pronephros, and then a mesonephros, whereas the permanent kidney is a new organ, the meta- nephros. Whether these glands represent modifications of an originally continu- ous organ, or whether they are three distinct structures, is undecided, but how- ever this may be, the pro-, meso-, and metanephroi of amniotes develop suc- cessively in the order named, both as regards time and place. THE PRONEPHROS The pronephros, when functional, consists of paired, segmentally arranged tubules, one end of each tubule opening into the ccelom, the other into a longitu- dinal pronephric duct which drains into the cloaca (Fig. 204 A). Near the nephrostome (the opening into the ccelom) knots of arteries project into the ccelom, forming glomeruli. Fluid from the ccelom and glomeruli and excreta from the cells of the tubules are carried by ciliary movement into the pronephric ducts. The human pronephros is vestigial. It consists of about seven pairs of rudi- mentary pronephric tubules, formed as dorsal sprouts from the nephrotomes (Fig. 205) in each segment, from the seventh to the fourteenth, and perhaps from more cranial segments as well. The nodules hollow out and open into the cclom. Dorsally and laterally, the tubules of each side bend backward and unite to form a longitudinal collecting duct (Fig. 204 B, A). The tubules first formed in the seventh segment begin to degenerate before those of the fourteenth segment have developed. Caudal to the fourteenth segment no pronephric tubules are devel- oped, but the free end of the collecting duct, by a process of terminal growth, ex- tends caudad beneath the ectoderm and lateral to the nephrogenic cord, until it 195 196 THE UROGENITAL SYSTEM A Pronephric duct B Mesodermal _] segments Neural tube Anlages of pronephric duct Nephrotome Somatic mesoderm Splanchnic mesoderm Pronephric tubule Celom Notochord Entoderm Fic. 204.—Diagrams showing the development of the pronephric duct and pronephric tubules (modi- fied from Felix). A shows a later stage than B. Neural tube. = ‘Mesodermal segment coe Cavity of segment Cavity of gut. Splanchnic mesoderm. Mesoderm of yolk sac. Fic. 205.—Transverse section of a 2.4 mm. human embryo showing the intermediate cell mass or nephrotome (Kollmann). reaches, and perforates, the lateral wall of the cloaca. Thus are formed the paired primary excretory (pronephric) ducts. The pronephric tubules begin to ra THE MESONEPHROS (197 appear in embryos of 1.7 mm., with nine or ten primitive segments (Felix, in Keibel and Mall, vol. 2); in 2.5 mm. embryos (23 segments) all the tubules have devel- oped and the primary excretory duct is nearly complete. In 4.25 mm. embryos the duct has reached the wall of the cloaca and soon after fuses with it. The pro- nephric tubules soon degenerate, but the primary excretory ducts persist and be- come the ducts of the mesonephroi, or mid-kidneys. THE MESONEPHROS The mesonephros, like the pronephros, consists essentially of a series of tubules, each of which at one end is related to a knot of blood vessels and at the other end opens into the primary excretory duct. Besides possessing an inter- nal glomerulus alone they differ from the pronephric tubules in that the nephro- tomes are transitory, never opening into the mesonephric chamber. The meso- nephric tubules arise just caudal to the pronephros and from the same general source, that is, the nephrotomes. Only a few of the more cranial tubules, how- ever, are formed from distinct intermediate cell masses, for caudal to the tenth pair of segments this mesoderm constitutes unsegmented, paired nephrogenic cords. These may extend caudally as far as the twenty-eighth segment. The primary excretory ducts lie lateral to the nephrogenic cords. When the developing mesonephric tubules begin to expand there is not room for them in the dorsal body wall and as a result this bulges ventrally into the coelom. ‘Thus there is produced on either side of the dorsal mesentery a longi- tudinal urogenital fold, which may extend from the sixth cervical to the third lumbar segment (Fig. 220). Later, this ridge is divided into a lateral mesonephric fold and into a median genital fold, the anlage of the genital gland. Differentiation of the Tubules.—The nephrogenic cord in 2.5 mm. embryos first divides into spherical masses of cells, the anlages of the mesonephric tubules. Four of these may be formed in a single segment. Appearing first in the 13th, 14th and 15th segments, the anlages of the tubules differentiate both cranially and caudally. In 5.3 mm. embryos the cephalic limit is reached in the sixth cervical segment, and thereafter degeneration begins at the cephalic end. Hence the more cranial tubules overlap those of the pronephros. In 7 mm. embryos the caudal limit is reached in the third lumbar segment. The spherical anlages of the tubules differentiate in a cranio-caudal direction (Fig. 206). First, vesicles with lumina are formed (4.25 mm.). Next, the vesicles elongate laterally, unite with the primary excretory ducts, and become S-shaped (4.9 mm.). The free, vesicular end of the tubule enlarges, becomes thin walled, 198 THE UROGENITAL SYSTEM and into this wall grows a knot of arteries to form the glomerulus (embryos of 5 to 7 mm.). The tubule, at first solid, hollows out and is lined with a low columnar epithelium. The outer wall of the vesicle about the glomerulus is Bowman’s capsule, the two constituting a renal corpuscle of the mesonephros (Fig. 206 D). ‘In the human embryo the tubules do not branch or coil as in pig embryos, consequently the mesonephros is relatively smaller. At 10 mm. about 35 Mesonephric duct Degenerating mesonephric cor puscle Degenerating mesonephri corpuscle and tubule Anlage of mesonephric tubule! a Glomerulus and Bowman’s, capsule Developing mesonephric cor puscle Urogenital sinus f esonephric duct AMetanephros Bowman’s capsule Fic. 206.—Diagrams showing the differentia- tion of the mesonephric tubules (modified after Felix). L., lateral; 1., median. Fic. 207.—Diagram showing the anlages of the urinary organs in about 10 mm. human embryos as seen from the left side (based on reconstructions by Keibel and Felix). tubules are present in each mesonephros and the glomeruli are conspicuous (Fig. 207). Each tubule shows a distal secretory portion and a proximal collect- ing part which connects with the duct (Fig. 208). The glomeruli form a single median column, the tubules are dorsal and the duct is lateral in position. Ventro-lateral branches from the aorta supply the glomeruli, while the posterior cardinal veins, dorsal in position, break up into a network of sinusoids about the tubules (see Chapter IX). THE METANEPHROS 199 The primary excretory duct, or mesonephric duct, is solid in 4.25 mm. em- bryos. A lumen is formed at 7 mm., wider opposite the openings of the tubules. The duct is important, as the ureteric anlage of the permanent kidney grows out from its caudal end, while the duct itself is transformed into the chief genital duct of the male, and its derivatives. The mesonephros is probably a functional ex- cretory organ in human embryos even though its tubules degenerate before the metanephros becomes functional (Bremer, Amer. Jour. Anat., vol. 19, 1916). Degeneration proceeds rapidly in embryos between 10 and 20 mm. long, begin- ning cranially. New tubules are formed at the same time caudally. In all, 83 pairs of tubules arise, of which only 26 pairs persist at 21 mm., and these are usu- ally broken at the angle between the collecting and secretory regions. They are Suprarenal gland Post. cardinal vein Collecting tubule Glomerulus Secretory tubule ? Beinn pepsi —Mesonephric duct v3 Miillerian duct Anlage of genital gland Fic. 208.—Reconstruction of the contents of the urogenital fold from transverse sections of a 12 mm. human embryo. X 95. divided into an upper group and a lower group. The collecting portions of the upper group, numbering 5 to 12, unite with the rete tubules of the testis or ovary. In the male they form the efferent ductules of the epididymis. In the female they constitute the epodphoron. Of the lower group a few tubules persist in the male, as the paradidymis with its canaliculus aberrans. In the female they form the paroophoron. t THE METANEPHROS ~ gh The essential parts of the permanent kidney are the renal corpuscles (glom- erulus with Bowman’s capsule), secretory tubules, and collecting tubules. The collecting tubules open into expansions of the duct, the pelvis and calyces. The duct itself is the ureter, which opens into the bladder. Like the mesonephros, the 200 THE UROGENITAL SYSTEM metanephros is of double origin. The ureter, pelvis, calyces, and collecting tubules are outgrowths of the mesonephric duct. The secretory tubules and the —Ouler zone Inner zone Bladder Fic. 209.—Reconstruction of the anlages of the metanephros in a human embryo of about 9 mm. (after Schreiner). The layers lettered Inner and Outer sone constitute the nephrogenic tissue of the metanephros. capsules of the renal corpuscles are differentiated from the isolated caudal end of the nephrogenic cord and thus have a similar origin as the mesonephric tubules. D Cranial pole tubule B Cranial Cranial pole tubule pole tubule Ventral central ) tubule Caudal pole Central ual Caudal tubule pole tubule Pelvis Secondary collecting ae tubules pole tubule Ureler Ureter Tertiary collecting tubule Fic. 210.—Diagrams showing the development of the primitive pelvis, calyces and collecting tubules of the metanephros (based on reconstructions by Schreiner and Felix). In embryos of about 5 mm. the mesonephric duct makes a sharp bend just before it joins the cloaca and it is at the angle of this bend that the ureteric evagi- THE METANEPHROS 201 nation appears, dorsal and somewhat median in position (Fig. 216 B, C). The bud grows at first dorsally, then cranially. Its distal end expands and forms the primitive pelvis. Its proximal elongated portion is the ureter. The anlage grows into the lower end of the nephrogenic cord (Fig. 209), which, in 4.6 mm. embryos, is separated from the cranial end of the cord at the twenty-seventh segment. The nephrogenic tissue forms a cap about the primitive pelvis, and, as the pelvis grows cranially, is carried along with it. In embryos of 9 to 13 mm. the pelvis, having advanced cephalad through three segments, attains a position in the retroperitoneal tissue dorsal to the mesonephros and opposite the second lumbar segment. Thereafter, the kidney enlarges both cranially and caudally without shifting its position. The ureter elongates as the embryo grows in length. The cranial growth of the kidney takes place dorsal to the suprarenal gland (Fig. 232). Primary collecting tubules grow out from the primitive pelvis in 10 mm. embryos. Of the first two, one is cranial, the other caudal in position, and between these there are usu- ally two others (Fig. 210 B, C). From an enlargement, the ampulla, at the end of each primary tubule grow out two, three, or four secondary tubules. These in turn give rise to tertiary tubules (Fig. 210 D) and the process is repeated until the fifth month of fetal life, when it is estimated that twelve generations of tubules have been developed. ‘The pelvis and Fic. 211.—Re- construction of the both primary and secondary tubules enlarge during develop- ureter, pelvis, caly- ces and their branch- es from the meta- calyces, and the secondary tubules opening into them form the _ nephros of a 16 mm. minor calyces (Fig. 211). The tubules of the third and fourth aera oe orders are taken up into the walls of the enlarged secondary tubules so that the tubules of the fifth order, 20 to 30 in number, open into the minor calyces as papillary ducts. The remaining orders of tubules constitute the ment. The first two primary tubules become the major collecting tubules which form the greater part of the medulla of the adult kidney. When the four to six primary tubules develop, the nephrogenic cap about the primitive pelvis is subdivided and its four to six parts cover the end of each pri- mary tubule. As new orders of tubules arise, each mass of nephrogenic tissue increases in amount and is again subdivided until finally it forms a peripheral layer about the ends of the branches tributary to a primary tubule. The con- verging branches of such a tubular “‘tree” constitute a primary renal unit, or pyramid, with its base at the periphery of the kidney and its apex projecting into 202 THE UROGENITAL SYSTEM the pelvis. The apices of the pyramids are termed renal papille and through them the larger collecting ducts open. The nephrogenic tissue forms the cortex of the kidney, and each subdivision of it, covering the tubules of a pyramid peripherally, is marked off on the surface of the organ by grooves or depressions. The human fetal kidney is thus distinctly lobated, the lobations persisting until after birth, a condition which is permanent in reptiles, birds, and some mammals (whale, bear, ox). The primary pyramids are subdivided into several secondary and tertiary pyramids. Between the pyramids the cortex of nephrogenic tissue dips down to the pelvis, forming the renal columns (of Bertin). The collecting tubules, on the other hand, extend out into the cortex as the cortical rays-or pars radiata of the cortex. In these rays, and in the medulla of the kidney, the collecting tubules run parallel and converge to the papille. 4 Fic. 212 —Semidiagrammatic figures of the anlage and differentiation of renal vesicles and early developmental stages of uriniferous tubules of mammals. 1 and 2, Anlage and successive stages in the differentiation of renal vesicles, as seen in sagittal sections; 3, section and outer form of tubular anlage before union with collecting tubule at the beginning of S-shaped stage; 4 and 5, successive stages in the development of the tubules, Bowman’s capsule, and glomerulus beginning with a tubular anlage showing a well-developed S shape (Huber). DIFFERENTIATION OF THE NEPHROGENIC TISSUE Os In stages from 13 to 19 mm., the nephrogenic tissue about the ends of the collecting tubules condenses into spherical masses which lie in the angles between DIFFERENTIATION OF THE NEPHROGENIC TISSUE 203, the buds of new collecting tubules and their parent stems (Fig. 212). One such metanephric sphere is formed for each new tubule. The spheres are converted into vesicles with eccentrically placed lumina. The vesicle elongates, its thicker outer wall forming an S-shaped tubule which unites with a collecting tubule, its thin inner wall becoming the capsule (Bowman’s) of a renal corpuscle. The uriniferous tubules of the adult kidney have a definite and peculiar structure and arrangement (Fig. 213 A). Beginning with a renal corpuscle, each tubule forms a proximal convoluted portion, a U-shaped loop (of Henle) with descending and Arch of collecting tubule A Arch of collecting tubule Distal convoluted tubule Stoerck’s loop Proximal convoluted Proximal convoluted tubule tubule Distal convoluted &, tubule fx" Renal cor puscle— Connecting piece Glomerulus Bowman’s capsule Connecting piece Ascending limb of. Henle’s loop Arch of collecting tubule Proximal convoluted tubule Distal convoluted tubule Descending limb of__| Connecting piece Henle’s loop Glomerulus Large collecting __| tubule | Fic. 213.—Diagrams showing the differentiation of the various parts of the uriniferous tubules of the metanephros (based on the reconstructions of Huber and Stoerck): A, From an adult human kid- ney; B, C, from human embryos. “— Bowman’s capsule Stoerck’s loop ascending limbs, a connecting piece, which lies close to the renal corpuscle, and a distal convoluted portion continuous with the collecting tubule. These parts are derived from the S-shaped anlage, which is composed of a lower, middle, and upper limb. The middle limb, somewhat U-shaped, bulges into the concavity of Bowman’s capsule (Fig. 213 B). By differentiation the lower portion of the lower limb becomes Bowman’s capsule, ingrowing arteries forming the glomerulus (Fig. 213 B, C). The upper part of the same limb by enlargement, elongation, and coiling becomes the proximal convoluted tubule. The neighboring portion of the middle limb forms the primitive loop (of Stoerck); the base of the middle ” 204 THE UROGENITAL SYSTEM Fic. 214.—Diagram showing the relation of Bowman’s capsule and the uriniferous tubules to the collecting tubules of the metanephros (Huber). c, Collecting tubules; e, end branches of collecting tubules; 7, renal corpuscles; ”, neck; fc, proximal convuluted tubule; di, descending limb of Henle’s loop, J; al, ascending limb of Henle’s loop; dc, distal convoluted tubule; j, junctional tubule. Fic. 215.—Several stages in the development of the uriniferous tubules and glomeruli of the human metanephros of the seventh month (reconstructions by Huber). x 160. limb gives rise to the connecting piece, and the rest of it, with the upper limb of the S, forms the distal convoluted tubule (intermediate piece of Felix). The prim- CLOACA, BLADDER, URETHRA AND UROGENITAL SINUS 205 itive loop of Stoerck includes both the ascending and descending limbs of Henle’s loop and a portion of the proximal convoluted tubule. Henle’s loop is differ- entiated during the fourth fetal month (Toldt) and extends from the pars radiata of the cortex into the medulla (Fig. 214). The concavity of Bowman’s capsule, into which grow the arterial loops of the glomerulus, is at first,shallow. Eventu- ally the walls of the capsule grow about and enclose the vascular knot, except at the point where the arteries enter and emerge (Fig. 212, 4 and 5). Renal cor- puscles are first fully formed in 28 to 30 mm. embryos. The new corpuscles are formed peripherally from persisting nephrogenic tissue until the tenth day after birth, hence in the adult the oldest corpuscles are those next the medulla. Recon- structions of the various stages in the development of the uriniferous tubules are shown in Fig. 215. Renal Arteries—One or more of the mesonephric arteries is transformed into the renal artery of the metanephros (Broman, 1906). As any one of the mesonephric arteries -may thus form the renal artery, and as they anastomose, the variation of the renal vessels both as to position and number is accounted for. Bremer (Amer. Jour. Anat., vol. 18, 1915) derives the renal arteries not from the mesonephric vessels but from a periaortic plexus of multiple aortic origin. \ Anomalies.—If the uriniferous tubules fail to unite with the collecting tubules, cystic degeneration may take place. The cystic kidneys of pathology may thus be produced. The nephrogenic tissue of the paired kidney anlagés may fuse, resulting in the union of their cortex (“horse-shoe kidney’’). Double or triple ureters and cleft ureters are sometimes present. DIFFERENTIATION OF CLOACA, BLADDER, URETHRA AND UROGENITAL SINUS In embryos of 1.4 mm. the cloaca, a caudal expansion of the hind-gut, is in contact ventrally with the ectoderm, and ectoderm and entoderm together form the cloacal membrane (Fig. 216 A). Ventro-cranially the cloaca gives off the allantoic stalk. At a somewhat later stage, the cloaca receives laterally the mesonephric ducts and caudally is prolonged as the tail-gut (Fig. 216 B). In embryos of 5 mm. the ureteric anlages of the metanephroi are present as buds of the mesonephric ducts (Fig. 216 C, D). Next, the saddle-like partition between the intestine and allantois grows caudally, dividing the cloaca into a dorsal rectum and ventral, primitive urogenital sinus. The division is complete in embryos of 11 to 15 mm., and at the same time the partition, fusing with the cloacal membrane, divides it into the anal membrane of the gut and the urogenital membrane. At 11 mm., according to Felix, the primitive urogenital sinus by elongation and constriction is differentiated into two regions: (1) a dorsal vesico-urethral anlage which receives the allantois and mesonephric duct, and 206 THE UROGENITAL SYSTEM A Hind-gut Hind-gut » Mesonephric duct ind-gut M. heric 5 Hind-gu ene Hindevik Allantois “» Cloacal membrane Tail-gut Fic. 216.—Four stages showing the differentiation of the cloaca into the rectum, urethra and bladder (after reconstructions by Pohlman). X about 50. A, from a human embryo of 3.5 mm.; B, at about 4 mm.; C, at 5mm.; D, at 7 mm. Mesonephric duct Intestine Fic. 217.—Reconstructions from a 12 mm. human embryo showing the partial subdivision of the cloaca into rectum and urogenital sinus (after Pohlman). X 65. CLOACA, BLADDER, URETHRA AND UROGENITAL SINUS 207 is connected by the constricted portion with (2) the phallic portion of the uro- genital sinus (Figs. 217 and 218). The latter extends into the phallus of both Celom Rectum Allantois Mesonephric ducts Vesico-urethral anlage Phallic portion of urogenital sinus | } HA an i ic Fic. 218.—Reconstruction of the caudal portion of an 11.5 mm. human embryo showing the differen- tiation of the rectum, bladder and urethra (after Keibel’s model). X 25. sexes and forms a greater part of the urethra (Fig. 219). The vesico-urethral anlage enlarges and forms the bladder and a portion of the urethra. In 7 mm. Genital gland Mesonephric fold Anlage of bladder, Vag Mesonephros Ureter Utero-vaginal anlage Mesonephric duct Rectum Anal membrane —“4rrrn 2 Rectum Fic. 219.—Reconstruction of the caudal end of a 29 mm. human embryo showing the complete separation of therectum and urogenital sinus and the relations of the urogenital ducts (after Keibel’s model). X 15. embryos the proximal ends of the mesonephric ducts are funnel shaped, and at 10 mm., with the enlargement of the bladder, these ends are taken up into 208 THE UROGENITAL SYSTEM its wall until the ureters and mesonephric ducts acquire separate openings. The ureters, having previously shifted their openings into the mesonephric ducts from a dorsal to lateral position, now open into the vesico-urethral anlage lateral to the mesonephric ducts. The lateral walls of the bladder anlage grow more rap- idly than its dorso-median urethral wall, hence the ureters are carried cranially and laterally upon the wall of the bladder, while the mesonephric ducts, now the male ducts, open close together on a hillock, Miiller’s tubercle, into the dorsal wall of the urethra (Fig. 219). The fate of the phallic portion of the urogenital - sinus is described on p. 226 in connection with the external genitalia. The apex of the bladder, continuous with the allantoic stalk at the umbilicus, is known as the urachus. Usually the epithelium of the urachus degenerates, but portions may persist and produce cysts. In some cases it forms after birth a patent tube opening at the umbilicus. Its connective tissue layers always persist-as the fibrous lig. wmbilicale medium. The transitional epithelium of the bladder appears at 60 mm. (C H). The outer longitudinal layer of smooth muscle develops in 22 mm. embryos, and, in 26 mm. embryos, the circular muscle appears. The inner Jongitudinal muscle layer is found at 55 mm. (C H) and the sphincter vesice in fetuses of 90 mm. (C H). Anomaly.—A conspicuous malformation is that of a persistent cloaca, due to the failure of the rectum and urogenital sinus to separate. THE GENITAL GLANDS AND DUCTS—INDIFFERENT STAGE In origin and early development, the ovary and testis are identical. The urogenital fold (p. 197) is the anlage of both the mesonephros and the genital gland (Figs. 122 and 220). At first two-layered, its epithelium in embryos of 5 mm. thickens over the ventro-median surface of the fold, becomes many- layered, and bulges into the ccelom ventrally, producing the longitudinal genztal fold. The genital fold thus lies mesial and parallel to the mesonephric fold. Large primitive sex cells are found in 2.5 mm. embryos in the entoderm of the future intestinal tract (Fuss). At 3.5 mm. they migrate into the dorsal mesen- teric epithelium and thence into the epithelium of the genital fold. At 10 to 12 mm. the genital epithelium shows no sexual differentiation (Fig. 221). There is a superficial epithelial layer and an inner epithelial mass of somewhat open structure. Owing to the great development of the suprarenal glands and metanephroi, the cranial portions of the urogenital folds, at first parallel and close together, are displaced laterally. This produces a double bend in each fold which, in 20 mm. embryos, shows a cranial longitudinal portion, a transverse middle portion between the bends, and a longitudinal caudal portion. In the last named segment, the mesonephric ducts course to the cloaca and here the right and left folds fuse, THE GENITAL GLANDS AND DUCTS—INDIFFERENT STAGE 209 Mesencephalon Prosencephalon Rhombencephalon Heart Right lung Esophagus Genital fold Mesonephric fold Genital eminence Lower extremity Tail Lateral body wall Post. cardinal vein Suprarenal gland Glomerulus Mesonephric duct Mesentery—* ‘ Fic. 221.—Transverse section through the mesonephros, genital gland and suprarenal gland of the right side; from a12mm.humanembryo. X 165. 14 210 ; THE UROGENITAL SYSTEM producing the genital cord (Fig. 232). As the genital glands increase in size they become constricted from the mesonephric fold by lateral and mesial grooves until the originally broad base of the genital fold is converted into a stalk (Figs. 225 to 227). This stalk-like attachment extends lengthwise and forms in the male the mesorchium, in the female the mesovarium. ‘The urogenital fold is, at the same time, constricted from the dorsal body wall until it is attached only by a narrow mesentery which eventually forms either the ligamentum testis or lig. ovarii. The Indifferent Stage of the Genital Ducts.—The mesonephric ducts, with the degeneration of the mesonephroi, become the male genital ducts. In both Mesonephric tubule Genital gland Fic. 222.—Transverse sections through the anlage of the right Miillerian duct from a 10 mm. human embryo. X 250. A, showing the groove in the urogenital epithelium; B, three sections caudad showing the tubular anlage of the duct. sexes there also develop a pair of female ducts (of Miiller). In embryos of 10 mm. the Miillerian ducts develop as ventro-lateral thickenings of the urogenital epithelium at the level of the third thoracic segment and near the cranial ends of the mesonephroi. Next, a ventro-lateral groove appears in the epithelium of the mesonephric fold (Fig. 222 A). Caudally, the dorsal and ventral lips of the groove close and form a tube which separates from, and lies beneath, the epithelium (Fig. 222 B). Cranially, the tube remains open as the funnel-shaped ostium abdominale of the Miillerian duct. The solid end of the tube grows caudalward beneath the epithelium, lateral to the mesonephric or male ducts (Figs. 223 to 225). Eventually, by way of the genital cord, the Miillerian THE GENITAL GLANDS AND DUCTS—INDIFFERENT STAGE 211 —— Pulmonary trunk Pulmonary artery Diaphragm Ostium abdominale Miillerian duct Esophagus Inferior vena cava Mesonephric duct Genital gland Mesonephros Colon Allantois Umbilical artery Trachea ere an oat / SS eee Cun Mesonephros Miutllerian duct Colon Umbilical artery Fic. 224.—Ventral dissection of a 24 mm. pig embryo showing the anlages of the Miillerian ducts at a later stage of development than in Fig. 223. X 6. 212 THE UROGENITAL SYSTEM ducts reach the median dorsal wall of the urogenital sinus and open into it (Figs. 219 and 238 A). Their further development into uterine tubes, uterus, and vagina is described on page 219. Embryos not longer than 12 mm. are thus character- ized by the possession of indifferent genital glands and of both male and female genital ducts. There is as yet no sexual differentiation. The development and position of the Miillerian ducts is well shown in ventral dissections of pig em- bryos (Figs. 223 and 224); the mesonephroi of the pig are of enormous size. In the lowest vertebrates the Miillerian duct arises by a longitudinal splitting of the mesonephric duct. Mesentery Mesone phric tubule Mesonephric duct Mesorchium Anlage of rete testis Intermediate cord Testis cord Epithelium Tunica albuginea Fic. 225.—Transverse section through the left testis and mesonephros of a 20 mm. human embryo. x 250. Differentiation of the Testis.—In the male embryos of 13 mm. the genital glands show two characters which mark them as testes: (1) the occurrence of branched, anastomosing cords of cells, the ¢estis cords: (2) the occurrence between epithelium and testis cords of a layer of tissue, the anlage of the tunica albuginea (Fig. 225). According to Felix, the testis cords are developed suddenly from the loose, inner epithelial mass by a condensation of its cells. The cords converge and grow smaller towards the mesorchiurh, where they form the dense, epi- thelial anlage of the rete testis. Two or three layers of loosely arranged cells between the testis cords and the epithelium constitute the anlage of the tunica albuginea. According to Allen (Amer. Jour. Anat., vol. 3, 1904), the testis cords THE GENITAL GLANDS AND DUCTS—TESTIS 213 of the rabbit and pig are formed as active ingrowths of cellular cords from the epithelium. The testis cords soon become rounded and are marked off by connective tissue sheaths from the intermediate cords, columns of undifferentiated tissue which lie between them (Fig. 226). Toward the rete testis the sheaths of the testis cords unite to form the anlage of the mediastinum testis. The testis cords are composed chiefly of indifferent cells with a few larger genital cells. The cells gradually arrange themselves radially about the inside of the connective tissue sheath as a many-layered epithelium, in which, during the seventh month, a lumen appears. The lumina appear in the peripheral ends of the testis cords, and, extending toward the rete testis, meet lumina which have formed there. Thus the solid cords of both are converted into tubules. The distal portions of Ductus deferens 5 Epithelium Mesorchium Intermediate cords Tunica albuginea {_ Testis cord Genital cell Fic. 226.—Section through the testis of a 100 mm. human fetus. X 44. the testis tubules anastomose and form the éubulz contorti. Their proximal por- tions remain straight as the tubuli recti. The rete testis becomes a network of small tubules which finally unite with the collecting tubules of the mesonephros (see p. 218). The primitive genital cells of the testis cords form the spermatogonia of the spermatic tubules and from these at puberty are developed the later generations of spermatogonia (p. 14). The indifferent cells of the tubules become the sus- tentacular cells (of Sertoli) of the adult testis. Primitive genital cells of the inter- mediate cords are transformed into large pale cells, which, after puberty, are numerous in the interstitial connective tissue and hence are called inéerstitial cells. The intermediate cords themselves are resorbed, but the connective tissue sheaths of the tubules unite to form septula which extend from the mediastinum 214 THE UROGENITAL SYSTEM testis to the tunica albuginea. The latter becomes a relatively thick layer in the adult testis and is so called because of its whitish appearance. Anomalies.-—The testis may be congenitally absent; the glands may be fused; or they may fail to descend into the scrotum (cryptorchism). Duplication of the testis is rare. The Differentiation of the Ovary.—The primitive ovary, like the testis, consists of an inner epithelial mass bounded by the parent peritoneal epithelium. The ovarian characters appear much more slowly than in the testis. In fetuses of 50 to 80 mm. (C H) the inner epithelial mass, composed of indifferent cells and primitive genital cells, becomes less dense centrally and bulges into the mesovarium (Fig. 227). There may be distinguished a dense, outer cortex beneath Tubules of mesonephros (Paroiphoron) Uterine (Miil- lerian) tube © Rete ovarii Genital cells Epithelium Medulla Cortex Fic. 227.—Section of an ovary from a 65 mm. human fetus. X 44, the epithelium, a clearer medullary zone containing large genital cells, and a dense, cellular anlage in the mesovarium, the primitive rete ovarii, which is the homologue of the rete testis. No epithelial cords and no tunica albuginea are developed at this stage, as in the testis. Later, three important changes take place: (1) There is an ingrowth of connective tissue and blood vessels from the hilus, resulting in the formation of a mediastinum and of septula. (2) Most of the cells derived from the inner epithelial mass are transformed into young cva, the process extending from the rete ovarii peripherally (Fig. 227). (3) In fetuses of from 80 to 180 mm. (C R) length the ovary grows rapidly, owing to the formation of a new peripheral zone of cells, perhaps derived in part from the peritoneal epithelium. At the end of this period the septule line the epithelium with a fibrous sheath, the anlage of the tunica albuginea. Hereafter, although THE GENITAL GLANDS AND DUCTS—OVARY 215 folds of the epithelium are formed, these do not penetrate beyond the tunica albuginea, and all cells derived from this source subsequently degenerate. This new peripheral zone, according to Felix, is always a single cellular mass in man, cords or “Pfliiger’s tubes” never growing in from the epithelium. Generally it has been believed that the primary follicles are derived from the subdivision of such cords. Coincident with the origin of a new zone of cells at the periphery of the ovary goes the degeneration of young ova in the medulla. By the ingrowth into this Primordial egg oe Germinal epithelium p Tunica albuginea Primordial ovum a, Phitiger’s egg tubes Blood vessel Primordial ova ~ Fic. 228.—Ovary of five-months’ fetus, showing primordial follicles (De Lee). region of connective tissue septa, the ova are separated into clusters or cords, the genital cells of which all degenerate, leaving in the medulla only a stroma of con- nective tissue. Late in fetal life indifferent cells, by surrounding the young ova of the cortex, produce primordial follicles (Fig. 229 A). During the first year after birth the primitive follicles are transformed into the vesicular (Graafian) follicles. By cell division the follicle cells form a zone many layers deep about the young ovum (Fig..229 B). Next a cavity appears in the sphere of follicle cells, enlarges, and produces a vesicle filled with fluid (Figs. 3 and 230). The 216 THE UROGENITAL SYSTEM ES FSAOt oN a ~“ \ SS We ‘ Ws Wen 5, t a Theca folliculi Z > Ect. Fig. 256) and shows three regions: a om : (1) the atrium, which receives the blood from the primitive veins; (2) the ventricle; (3) the bulb, from which is given off the ventral aorta. Ms. spl. End. B Fic. 255.—Diagrams to illustrate the origin of Fic. 256.—The heart of a 2 mm. human the mammalian heart. ct., Ectoderm; End., endo- embryoin ventral view (Mall). X65. The thelial tubes; Eni., entoderm; Fg.,-fore-gut; Msc.d., open tube is the fore-gut. dorsal mesocardium; Ms.spl., splanchnic mesoderm (epi- and myocardium). As the cardiac tube grows faster than the pericardial cavity in which it lies it bends to the right, the bulbus and ventricle forming a U-shaped loop (Fig. 257). Four regions may now be distinguished: (1) the sinus venosus; (2) the atrium, also thin walled and lying cranial to the sinus; (3) the thick-walled ventricu- lay limb, ventrad and caudad in position; (4) the bulbar limb, cranial to the ventric- ular limb and separated from it by the bulbo-ventricular cleft. Next, in embryos 250 THE DEVELOPMENT OF THE VASCULAR SYSTEM of 3 to4 mm., the bulbo-ventricular loop shifts its position until its base is directed caudad and ventrad (Fig. 257 B). At the same time the sinus venosus is brought dorsal to the atrium, which in turn is cranial with relation to the bulbo-ventricular A B Fic. 257.—A, Heart of human embryo of 2.15 mm.: a, Bulbus cordis; b, primitive ventricle; c, atrial portion. B, Heart of human embryo of about 3 mm.: a, Bulbus cordis; 6, atrial portion (behind); c, primitive ventricle (in front). Ventral views (His). loop, and the bulbar limb is pressed against the ventral surface of the atrium and constricts it (Fig. 258 A). In embryos of 4 to 5 mm. the right portion of the sinus venosus grows more rapidly than the left, this being due to the fact that the blood flow of the left A Fic. 258.—A, Heart of human embryo of about 4.3 mm.: «, Atrium; 6, portion of atrium corre- sponding to auricular appendage; c, bulbus cordis; d, atrial canal; c, primitive ventricle. B, Heart of human embryo of about 10 mm.: a, Left atrium; , right atrium; c, bulbus cordis; d, interventricular groove; ¢, right ventricle; f, left ventricle. Ventral views (His). umbilical vein is shifted to the right side through the liver. As a result, the en- larged right horn of the sinus opens into the right dorsal wall of the atrium through a longitudinally oval foramen, which is guarded on the right by a vertical fold. EARLY DEVELOPMENT OF THE HEART AND PAIRED BLOOD VESSELS 251 This fold, which projects into the atrium, is the right valve of the sinus venosus. Later, a smaller fold forms the left valve of the sinus venosus (Fig. 260 B). The atrium is constricted dorsally by the gut, ventrad by the bulbus. It therefore must enlarge laterally and in so doing forms the right and left atria (Fig. 258 A, B) with the distal portion of the bulb between them. The deep external groove between the atria and the bulbo-ventricular part of the heart is the coronary sulcus. As the bulbo-ventricular region increases in size, the duplication of the wall between the two limbs lags behind in development and finally disappears (Fig. 259), leaving the proximal portion of the bulb and the ventricular limb to form a single chamber, the primitive ventricle. In an embryo of 5 mm. the heart is thus composed of three undivided chambers: (1) the sinus venosus, opening dorsad into the right dilation of the atrium; (2) the bilaterally dilated atrium, Pulmonary artery Aorta } a Atrium Bulbus---% (/ -- L. ventricle R. ventricle .. . R. ventricle.- Fic. 259.—Diagrams to show the reduction of the bulbo-ventricular fold (represented by diagonal lines) due to its retarded development. (Modified after Keith.) opening by the single transverse atrial canal into (3) the primitive undivided ven- tricle. The three-chambered heart is persistent in adult fishes, but in birds and mammals a four-chambered heart is developed in which venous blood circulates on the right, and arterial blood on the left. In amphibians and reptiles transi- tional types occur. The important changes leading to the formation of the four-chambered heart are: (1) the complete division of the atrium and ventricle, each into right and left chambers; (2) the division of the bulb and its distal continuation, the truncus arteriosus, into the aorta and pulmonary artery; (3) the incorporation of the sinus venosus into the wall of the right atrium; (4) the development of the semilunar and atrio-ventricular valves. The first of these changes is completed only after birth. Endocardial Cushions and Atrial Septa.—In embryos of 5 to 7 mm. there 252 THE DEVELOPMENT OF THE VASCULAR SYSTEM develops a thin sickle-like membrane from the mid-dorsal wall of the atrium (Figs. 260 and 261). This is called the atrial septum primum (I). Simultaneously, endothelial thickenings appear in the dorsal and ventral walls of the atrial canal (Figs. 261 A, B). There are the endocardial cushions, which later fuse, thus ; Valves of sinus venosus Valves of sinus venosus Septum I x oramen ovale L Atrium Sept I Atrio-ventricular canal Atrio-ventric- ular canal Interventricular sepium Sinus venosus R. valve of sinus venosus Fic. 260.—Horizontal sections through the chambers of the human heart: A, 6 mm.; B,9mm.; C, 12 mm. (A and B are based on figures of Tandler.) about 50. dividing the single atrial canal into right and left atrio-ventricular canals (Fig. 266). The atrium is now partly divided into right and left atria, which, how- ever, communicate ventrad through the interatrial foramen. Next, in embryos of 9mm., the septum I thins out dorsad and cephalad and asecond opening appears, EARLY DEVELOPMENT OF THE HEART AND PAIRED BLOOD VESSELS 253 the foramen ovale (Figs. 260 and 261 B). The atria are now connected by two openings, the interatrial foramen and the foramen ovale. Soon (embryos of 10 to 12 mm.) the ventral and caudal edge of septum I fuses with the endocardial cushions, which have in turn united with each other (Figs. 260 and 261 C). The interatrial foramen is thus obliterated, but the foramen ovale persists until after birth. In embryos of 9 mm. the septum secundum (IT) is developed from the dorsal and cephalic wall of the atrium, just to the right of the septum primum (Fig. 260 C). It is important, as it later fuses with the left valve of the sinus venosus and with it forms a great part of the atrial septum of the late fetal and adult heart. L.atr. Fic. 261.—Lateral dissections of the human heart viewed from the left side: A,6mm.; B, 9 mm.; C,12mm. (B is based on a reconstruction by Tandler.) X about 38. Cor. sin., Coronary sinus; D. end. c., dorsal endocardial cushion; For. ov., foramen ovale; Int. for., interatrial foramen; I. v. ¢., inferior vena cava; L. aér., left atrium; L. va.s.v., left valve of sinus venosus; L. vent., left ventricle; Pul.a., pulmonary artery; Pul.v., pulmonary vein; Sept. I, Sept. II, septum primum, septum secundum; Sup. v. v., superior vena cava; V. end. c., ventral endocardial cushion. Sinus Venosus and its Valves.—The opening of the sinus venosus into the dorsal wall of the right atrium is guarded by two valves (Fig. 260). Along the dorsal and cephalic wall of the atrium these unite to form the septum spurium. Caudally the valves flatten out on the floor of the atrium, but, as stated pre- viously, the left valve later fuses with the atrial septum II. In embryos of 10 to 20 mm. the atria increase rapidly in size and the lagging right horn of the sinus venosus is taken up into the wall of the right atrium. By this absorption the superior vena cava now opens directly into the cephalic wall of the atrium, the inferior vena cava into its caudal wall (Fig. 261 C). The transverse portion of the sinus venosus, persisting as the coronary sinus in part, opens into the pos- terior wall of the atrium. 254 THE DEVELOPMENT OF THE VASCULAR SYSTEM The right valve of the sinus venosus is very high in 10 to 65 mm. embryos (first to third month) and nearly divides the atrium into two chambers (Fig. 262). It becomes relatively lower during the third and fourth months. Its cephalic portion becomes the rudimentary crista terminalis (Fig. 263); the remainder is divided by a ridge into two parts, of which the larger cephalic division persists as the valve of the inferior vena cava (Eustachian valve) located at the right of the opening of the vein, and the smaller caudal portion becomes the valve of the coro- nary sinus (Thebesian valve). Foramen ovale ZL <“——~€& Sup. vena cava a Seplum II R. valve of sinus venosus Inf. vena cava- Semilunar valve of pulmonary artery Septum I R. ventricle Fic. 262.—Lateral dissection of the heart of a 65 mm. human fetus viewed from the right side. xX 12. The Jeft valve of the sinus venosus becomes continuous with the septum se- cundum, and, in embryos of 20 to 22 mm. or larger, the two bound an oval opening (Figs. 263 to 265). The bounding wall of the oval aperture is the limbus ovalis. Closure of the Foramen Ovale.—The free edge of septum I is, in embryos of 10 to 15 mm., directed dorsad and cephalad (Fig. 261 C). Gradually, in later stages (Figs. 264 and 265), its caudal and dorsal prolongation grows cephalad and ventrad until its free edge is so directed. Coincident with this change the septum II, with its free edge directed at first ventrad and caudad, shifts until its free edge is directed dorsad and cephalad, and overlaps the septum I (Figs. 261 C, EARLY DEVELOPMENT OF THE HEART AND PAIRED BLOOD VESSELS 255 264 and 265). The opening between these septa persists until after birth as the foramen ovale. During fetal life the left atrium receives little blood from the lungs, so that the pressure is much greater in the right atrium. As a result, the septum I is pushed to the left and the blood flows from the right into the left atrium through the foramen ovale. After birth,-the left atrium receives from the expanding lungs as much blood as the right atrium, the septum I is pressed against the limbus of Crista terminalis Sept. II+-L. valve of SINUS VENOSUS Septum I Inf. vena cava Valve of inf. vena cava. Semilunar valves Valve of coronary sinus of pulmonary artery , ; R. ventricle Tricuspid valve Katherine Hills Fic. 263.—Lateral dissection of the heart of a 105 mm. human fetus viewed from the right side. X 7. septum II, and soon fuses with it. The depression formed by the thinner walled septum I is the fossa ovalis. The foramen ovale may fail to close soon after birth and the mixed blood produces a purplish hue in the child which is known popularly as a “blue baby.” This condition may be persistent in adult life. Incomplete closure occurs in about one in four cases, but actual mingling of the blood is rare, due to an approximation of the overlapping septal folds during atrial systole. ; Pulmonary Veins.—In embryos of 6 to 7 mm. a single vein (arising in the cat from a peripulmonary plexus, Brown, Anat. Rec., vol. 7, 1913) drains into THE DEVELOPMENT OF THE VASCULAR SYSTEM Septum II Foramen ovale Sup. vena cava Seplum I Aorta | (ode Pulmonary trunk > G4 on Coronary sinus (A Bicus pid valve oO | est entricle mao L. atrium Fic. 264.—Lateral dissection of the heart of a 65 mm. human fetus viewed f om the left ide, showing the septa and the foramen ovale. X 8. Sup. v. c. For. ov. For. ov. Sup. v. C. Aorta L. atr. vent. C. L. vent.A Fic. 265.—Lateral dissections of the human heart viewed from the left side: 4, from a 22 mm. embryo; B, froma 105 mm. fetus. Bic. va., Bicuspid valve; Cor. sin., coronary sinus; For. ov., foramen ovale; I.v.c., inferior vena cava; L. atr. vent. «., left atrio-ventricular canal; L. ven., left ventricle; Pu. a., pulmonary artery; Sept. I, Sept. 17, septum primum and septum secundum. EARLY DEVELOPMENT OF THE HEART AND PAIRED BLOOD VESSELS 257 the caudal wall of the left atrium at the left of the septum I (Fig. 261.C). This vein bifurcates into right and left pulmonary veins which divide again before Pulmonary arlery —— Aorla Incomplete bulbar septum Dorsal endocardial cushion Atrio-ventricular Ventral endocardial foramen cushion : WA Interventricular (|) septum mt Interventricular sulcus é C= Aorta oa iY > \\ yp Pulmonary artery Arrow in pulmonary artery B faba ase of aorta Proximal bulbar septum Arrow in aorta Interventricular foramen ' NL. atrio-ventricular R. atrio-ventricular foramen foramen ! | Interventricular Y] R. ventricle \— septum Fic. 266.—Ventral views of stages in the development of the heart to show the differentiation of the bulbus cordis into the aorta and pulmonary trunk (Kollman): A, Heart of a5 mm. human embryo; B, of a 7.5 mm. human embryo. entering the lungs. As the atrium grows, the proximal portion of the pulmonary vein is taken up into the atrial wall. As a result, at first two, then four pul- monary veins open into the left atrium. 17 258 THE DEVELOPMENT OF THE VASCULAR SYSTEM Origin of the Right and Left Ventricles.—In embryos of 5 to 6 mm. there appears at the base of the primitive ventricular cavity a sagittally placed eleva- tion, the interventricular septum (Fig. 260 B). It later grows cephalad and dorsad toward the endocardial cushions, and forms an incomplete partition be- tween the right and left ventricles, which still communicate through the persisting interventricular foramen (Fig. 266 B). Corresponding to the internal attach- ment of the septum there is formed externally the interventricular sulcus (Fig. 266 A) which marks the external line of separation between the large left ven- tricle and the smaller right ventricle. Origin of Aorta and Pulmonary Artery from Bulbus.—Coincident with the formation of the interventricular septum there arise in the aortic bulb (including its distal truncus arteriosus) longitudinal thickenings, four in the distal half, two in the proximal half. Of the four distal thickenings (Fig. 267), two, which may be OD: a Pulmonary artery Fic. 267.—Scheme showing division of bulbus cordis and its thickenings into aorta and pulmonary artery with their valves. (Explanation in text.) designated a and c, are larger than the other thickenings, b and d. Thickenings a and ¢, which distally occupy left and right positions in the bulb, meet, fuse, and divide the bulb into a dorsally placed aorta and ventrally placed pulmonary trunk (Fig. 266). Traced proximally they pursue a clockwise, spiral course, a shifting from left to ventral, and c from right to dorsal, both becoming con- tinuous with the proximal swellings. Thickenings b and d are also prominent at one point proximally; when the bulb in this region is divided by ingrowing con- nective tissue into the aorta and pulmonary artery, the aorta contains the whole of the thickenings } and half of a and c, while the pulmonary trunk contains the whole of d and half of a and ¢ (Fig. 267). Distally the three thickenings now pres- ent in each vessel disappear, but proximally they enlarge, hollow out on their distal surfaces, and eventually form the thin-walled semilunar valves (Fig. 267). The anlages of these valves are prominent in embryos of 10 to 15 mm. as plump swellings projecting into the lumina of the aorta and pulmonary artery. THE PRIMITIVE BLOOD VASCULAR SYSTEM 259 The two proximal bulbar swellings fuse and continue the spiral division of the bulb toward the interventricular septum in such a way that the base of the pul- monary trunk, now ventrad and to the right, opens into the right ventricle, while the base of the aorta, now lying to the left and dorsad, opens into the left ven- tricle close to the interventricular foramen, through which the two ventricles still communicate (Fig. 266 B). Closure of the Interventricular Foramen.—The interventricular foramen in embryos of 15 to 16 mm. is bounded: (1) by the interventricular septum; (2) by the proximal bulbar septum; and (3) by the dorsal portion of the fused endo- cardial cushions (Fig. 266). Soon these structures are approximated and fuse, thereby forming the septum membranaceum, which closes the interventricular foramen. The atrio-ventricular valves arise as thickenings of the endocardium and endocardial cushions of the atrio-ventricular foramina (Figs. 260 and 261). Three such thickenings are formed on the right, two on the left. The anlages of the valves are at first thick and project into the ventricles. Later, as the ven- tricular wall differentiates, the valvular anlages are undermined, leaving their edges attached to the ventricular walls by muscular trabecule, or cords. The muscle tissue of both the valves and trabecule soon degenerates and is replaced by connective tissue, forming the chorde tendinee of the adult valves. ‘Thus there are developed the three cusps of the tricuspid valve between the right chambers of the heart, and the two flaps of the bicuspid, or mitral valve, between the left atrium and left ventricle. Differentiation of the Myocardium.—The myocardium, at first uniformly spongy, becomes compact at the periphery. The inner bundles remain trestle-like, forming the trabecule carne and the papillary and moderator muscles around all of which the originally simple endocardial sac is wrapped. The myocardial layers, at first continuous over the sur- face of the heart, become divided by connective tissue at the atrio-ventricular canal, leaving a small bridge alone. This connecting strand, located behind the posterior endocardial cushion, forms the atrio-ventricular bundle. Descent of the Heart.—At first the heart lies far cephalad in the cervical region, but it gradually recedes during development until it assumes its permanent position in the thorax. PRIMITIVE BLOOD VASCULAR SYSTEM The first paired vessels of human embryos are formed as longitudinal anas- tomoses of capillary networks which, however, originate first in the angioblast of the yolk sac and chorion. In the Eternod embryo of 1.3 mm., in which the somites are still undeveloped the paired vessels are already formed (cf. Fig. 268). They are the umbilical veins which emerge from the chorion, fuse in the body stalk, then, separating, course in the somatopleure to. the paired tubular heart. From the 260 THE DEVELOPMENT OF THE VASCULAR SYSTEM heart tubes paired vessels, the ventral aorte, extend cephalad, then bend dorsad as the first aortic arches and extend caudad as the dorsal or descending aorte. These, as the umbilical arteries, bend sharply ventrad into the belly stalk aad branch Dorsal intersegmental arteries Descending aorte Umbilical veins Primitive aortic arch Primitive heart Fiody site Vitello-wmbilical trunk Umbilical vein as . Yolk sac Vitelline arteries Frc. 268.—Diagram, in lateral view, of the primitive blood vessels in human embryos of 1.5 to 2 mm. in the wall of the chorion. The chorionic circulation is thus the first to be es- tablished. In embryos 2 to 2.5 mm. long (5 to 8 somites) the heart has become a single tube (Fig. 269). From the yolk sac numerous veins converge cephalad and form a pair of vitelline veins. These join the umbilical veins, and, as the vitello-umbili- Dorsal intersegmental arteries Ant. cardinal veins Descending aorte Umbilical arteries Aortic arch 1 Heart Vitello-umbilical trunk oe . Vitelline veins Vitelline arteries Yolk sac Fic. 269.—Diagram, in lateral view, of the primitive blood vessels in human embryos of 2 to 2.5 mm. cal trunk, traverse the septum transversum and open into the sinus venosus. The descending aortz give off, dorsally and cranially, several pairs of dorsal intersegmental arteries, and, ventrad and caudad, a series of non-segmental vitelline arteries to the yolk sac. The umbilical arteries now take their origin from a DEVELOPMENT OF THE ARTERIES 261 plexus of ventral vessels in series with the vitelline arteries. At this stage the vitelline circulation of the yolk sac is established. In embryos of 15 to 23 somites (Fig. 270) the vezms of the embryo proper de- velop as longitudinal anastomoses of branches from the segmental arteries. The paired anterior cardinal veins of the head are developed first, and, coursing back on either side of the brain, they join the vitello-umbilical trunk. In embryos of 23 somites the posterior cardinals are present. They lie dorsal to the nephrotomes, and, running cranially, join the anterior cardinal veins to form the common cardinal veins. Owing to the later enlargement of the sinus venosus, the proximal portions of the common venous trunks are taken up into its wall and thus three veins open into each horn of the sinus venosus: (1) the wmbilical veins from the chorion; (2) the vitelline veins from the yolk sac; (3) the common cardinal veins from the body of the embryo. Posterior cardinal veins Ant. cardinal veins Vitelline artery Descending aorta Umbilical arteries, Aortic arches 1 and 2 Sinus venosus Vitelline veins Fic. 270.—Diagram of the blood vessels of human embryos of 2.6 mm. The descending aorte have now fused caudal to the seventh intersegmental arteries and form the single dorsal aorta as far caudad as the origins of the um- bilical arteries. Of the numerous vitelline arteries one pair is prominent; these fuse into a single vessel which courses in the mesentery and later becomes the superior mesenteric artery. By the enlargement of capillaries connecting the ventral and dorsal aortz a second pair of aortic arches is formed at this stage (Fig. 270): DEVELOPMENT OF THE ARTERIES Transformation of the Aortic Arches.—In embryos 4 to 5 mm. in length five pairs of aortic arches are successively developed, the first, second, third, fourth, and sixth (Fig. 271). An additional pair of transitory vessels which extend from 262 THE DEVELOPMENT OF THE VASCULAR SYSTEM the ventral aorta to the sixth arch appear later in embryos of 7 mm., but soon degenerate (Fig. 272 B). They are interpreted as being the fifth pair in the series. From each dorsal or descending aorta there develop cranially the internal carotid arteries. These extend toward the optic stalks where they bend dorsad and caudad, connecting finally with the first intersegmental arteries of each side (Fig. 271). The descending aortz are now fused to their extreme caudal ends and the umbilical arteries take their origin ventrally. Twenty-seven pairs of dorsal 3 ‘ Vertebral artery First cervical artery Otocyst 4 ( ) IN, a) Pulmonary artery Ant. cardinal vein Vena capitis medialis aw ers Post. cardinal vein - Bulbus cordis Subclavian artery | Ophthalmic artery Celiac artery Ant. cerebral artery Common cardinal vein Vitelline artery (Superior mesenteric) Caudal artery Umbilical artery Inf. mesenteric artery Fic. 271.—Arteries and cardinal veins of the right side in a 4.9 mm. human embryo (modified after Ingalls). XX 20. H, Heart; I-VI, aortic arches. intersegmental arteries are present. From the seventh cervical pair of these the subclavian arteries of the upper limbs arise. Of the ventral vitelline vessels three are now prominent, the celiac artery in the stomach-pancreas region, the vitelline or superior mesenteric in the small intestine region, and the inferior mesen- teric of the large intestine region. Of the aortic arches the third pair is largest at 5 mm. (Fig. 272, A). From the sixth pair are given off the small pulmonary arteries to the lungs. At 7 mm. the first and second aortic arches are obliterated (Figs. 272 B and 273), but the DEVELOPMENT OF THE ARTERIES 263 dorsal and ventral aorte cranial to the third arch persist as parts of the internal and external carotid arteries respectively. The third arches form the stems of the internal carotids, while the ventral aorte between the third and fourth arches become the common carotids. In embryos of 15 mm. the bulbus cordis has been divided into the aortic and pulmonary trunks, so that the aorta opens into the left ventricle and the pulmonary trunk into the right ventricle. The dorsal * aorte between the third and fourth arches disappear, but the fourth arch on the Dorsal aorta Aortic arch 4 Aortic arch 6 Esophagus Trachea Pulmonary artery Ventral aorta Bulbus cordis B Aortic arch 3 Int. carotid artery Aortic arch 2 External carotid Aortic arch 6 Pulmonary artery Bulbus cordis SS \ Fic. 272.—Aortic arches of human embryos: A, of 5mm.; B, of 7 mm. (after Tandler). I-JV, pharyn- geal pouches. left side persists as the aortic arch of the adult. On the right side, the fourth aortic arch persists with the descending aorta as far as the seventh intersegmental artery and forms part of the right subclavian artery, which is thus longer than the left. The segment of the fourth arch proximal to the right common carotid becomes the innominate artery. On the right side, the sixth arch between the origin of the right pulmonary artery and descending aorta is early lost; on the left side, it persists as the ductus arteriosus and its lumen is only obliterated after birth. The . 264. THE DEVELOPMENT OF THE VASCULAR SYSTEM proximal portion of the right sixth arch forms the stem of the right pulmonary artery, but the proximal portion of the Jeft arch is incorporated in the pulmonary trunk. The aortic arches of the embryo are of especial importance comparatively. Five arches are formed in connection with the gills of adult fishes. In adult tailed amphibia, three or four arches, and in some reptiles two arches, are represented on either side. In birds the right, in mammals the left fourth arch persists as the arch of the aorta. The different courses of the recurrent laryngeal nerves are easily explained. The vagus early gives off paired branches which reach the larynx by passing caudal to the primitive fourth aortic arches. When the latter, through growth changes, descend into the chest, loops of both nerves are carried with them. Hence, after the transformation of the fourth arches, the left recurrent nerve remains looped around the arch of the aorta, the right around the right subclavian artery (cf. Fig. 273). External carotid Internal carotid Innominate Common carotid artery Aortic arch Right sub- clavian artery Right pul- Sag monary artery f Ductus arteriosus Vertebral artery Subclavian artery Trunk of pul- Left pul jane bees oft pulmonary artery Ventral aorta Fic. 273.—Diagram showing the aortic arches and their derivatives in human embryos. Branches of the Dorsal Aorta—From the primitive aorte arise: (1) dorsal, (2) lateral, and (3) ventral branches (Fig. 274). 1. The dorsal branches are intersegmental and develop small dorsal and large ventral rami. From the dorsal rami are given off neural branches which bifurcate and form dorsal and ventral spinal arteries. Origin of the Vertebral Arteries and Basilar Artery.—As we have seen (Fig. 271), the internal carotids are recurved cranially in the 5 mm. embryo and anas- tomose with the first two pairs of dorsal intersegmental arteries. By longitudinal postcostal anastomoses (Fig. 274) of the dorsal rami of the first seven pairs of dor- sal intersegmental arteries the vertebral arteries arise (Fig. 275). The original trunks of the first six pairs are lost so that the vertebrals take their origin with the . DEVELOPMENT OF THE ARTERIES 205 Postcostal anastomosis Precostal anastomosis Dorsal ramus Venibal eaanis Dorsal (intersegmental) artery Aorta Lateral (visceral) artery Ventral (splanchnic) artery Ventral anastomosis Fic. 274.—A diagram of the trunk, in transverse section, showing the arrangement of the aortic branches. ADCD. a Fic. 275.—The development of the vertebral and subclavian arteries and the costo-cervical trunk in a young rabbit embryo (modified after Hochstetter). III AB.—IV AB., Aorticarches; Ap, pulmonary artery; A.v.c.b. and A.v.c.v., cephalic and cervical portions of vertebral artery; A.s., subclavian artery; C.c., costo-cervical trunk; C.d. and C.v., internal and external carotid arteries; [.S.G., spinal ganglion. subclavians from the seventh pair of intersegmental arteries (Fig. 276). In embryos of 9 mm. the vertebrals in the region of the metencephalon fuse to form a single 266 THE DEVELOPMENT OF THE VASCULAR SYSTEM median ventral vessel, the basilar artery, which thus is connected cranially (by way of the circulus arteriosus) with the internal carotids, caudad with the verte- bral arteries. Fic. 276.—Arterial system of a human embryo of 10 mm. (His). > 18. Jc, Internal carotid artery; P, pulmonary artery; Ve, vertebral artery; 17 J-VI, persistent aortic arches. The internal carotids (Fig. 271), after giving off the ophthalmic arteries, give rise cra- nially to the anterior cerebral artery, from which arise later the middle cerebral artery and the anterior chorioidal artery, all of which supply the brain. Caudalward many small branches to the brain wall are given off and quite late in develop- ment (48 mm. C R fetuses) these form a true pos- terior cerebral artery (Mall). The ventral rami of the dorsal interseg- mental arteries become prominent in the thoracic and lumbar regions and persist as the intercostal and lumbar arteries, segmentally arranged in the adult. Longitudinal precos- tal anastomoses (Fig. 274) constitute the costo-cervical and thyreo-cervical trunks (Fig. 275). The subclavian and a portion of the internal mammary artery are derived from the ventral ramus of the seventh cervical seg- mental artery. The remainder of the internal Fic. 277.—The development of the : ; 2 2 internal mammary and deep epigastric ™ammary and the superior and inferior epi- arteries in a human embryo of 13mm. gastric arteries are formed by longitudinal (Mall in McMurrich). ventral anastomoses (Fig. 274) between the extremities of the ventral rami from the thoracic and lumbar intersegmental arteries, beginning with the second or third thoracic (Fig. 277). DEVELOPMENT OF THE ARTERIES 267 2. The lateral (visceral) branches of the descending aorte are not segmentally arranged. They supply structures arising from the nephrotome region (meso- nephros, sexual glands, metanephros, and suprarenal glands). From them later arise the renal, suprarenal, inferior phrenic, and internal spermatic or ovarian arteries. 3. The ventral (splanchnic) branches are at first rather definitely intersegmen- tal. Primitively they form the paired vitelline arteries to the yolk sac (Figs. 268 to 270). Coincident with the degeneration of the yolk sac the prolongations of the ventral vessels to its walls disappear, and the paired persisting arteries, passing in the mesentery to the gut, fuse to form unpaired vessels from which Seventh segmental artery Celiac arter > Tenth dorsal segmental artery V. pancreas Dorsal aorta Celiac axis Yolk stalk Vitelline artery Mesonephric arteries t Vitelline artery Dorsal aorta R. umbilical artery (¢ ae Cloaca pe Inf. mesenteric ad yg arlery Common iliac artery A B Fic. 278.—Reconstructions showing the development of the umbilical and iliac arteries (after Tandler): A, 5 mm. human embryo; B, 9 mm. human embryo. three large arteries are derived, the celiac artery, the superior mesenteric, and the inferior mesenteric (Fig. 271). The primitive cceliac axis arises opposite the seventh intersegmental artery. Together with the mesenteric arteries, it migrates caudalward until eventually its origin is opposite the twelfth thoracic segment (Mall). This migration, according to Evans, is due to the un- equal growth of the dorsal and ventral walls of the aorta. Similarly, the superior mesenteric artery is displaced caudad ten segments, the inferior mesenteric artery three segments. The Umbilical and Iliac Arteries.—As previously described, the umbilical arteries arise in young human embryos of 2 to 2.5 mm. from the primitive aorte opposite the fourth cervical segment. They take origin from a plexus of ventral 268 THE DEVELOPMENT OF THE VASCULAR SYSTEM vessels of the vitelline series (Fig. 270), and are gradually shifted caudalward until they arise from the dorsal aorta opposite the twenty-third segment (fourth lum- bar). In 5 mm. embryos the umbilical arteries develop secondary Jateral con- nections with the aorta (Fig. 278 A). The new vessels pass lateral to the mes- onephric ducts, and, in 7 mm. embryos, the primitive ventral stem-artery has disappeared. The segment of this new trunk, proximal to the origin of the exter- nal iliac artery which soon arises from it, becomes the common iliac. The re- mainder of the umbilical trunk constitutes the hypogastric artery. When the placental circulation ceases at birth, the distal portion of the hypogastric arteries, from pelvis to umbilicus, atrophy, forming the solid obliterated hypogastric arteries of adult anatomy. The middle sacral artery is the direct caudal continuation of the aorta. Its dorsal position is the result of secondary growth changes. Arteries of the Extremities.—It is assumed that in man, as in observed birds and mammals, the first vessels of the limb buds form a capillary plexus. Upper Extremity.—The capillary plexus takes origin by several lateral branches from the aorta. In human embryos of 5 mm. but one connecting vessel remains and this takes its origin secondarily from the seventh dorsal intersegmental artery, forming the ventral ramus of this artery and its lateral offset (Fig. 274). The portion of this vessel in what will become the free arm is plexiform at first, but later becomes a single stem which forms successively the subclavian, axillary, brachial, and interosseous arteries. Subsequently the median, radial, and ulnar arteries of the arm are formed. Arteries of the Lower Extremity.—In embryos of 7 mm. there is given off from the second- ary lateral trunk of the umbilical artery (i. e. from the future common iliac) a small branch which forms the chief arterial stem of the lower extremity, the future popliteal and peroneal arteries. This, the arteria ischiadica, is superseded in embryos of 15.5 mm. by the external iliac and femoral arteries, of which the latter annexes the branches of the ischiadic distal to the middle of the thigh. The arteria ischiadica persists proximally as the inferior gluteal artery. DEVELOPMENT OF THE VEINS We have seen that in embryos of 23 somites three systems of paired veins are present, the umbilical veins from the chorion, the vitelline veins from the yolk sac, and the cardinal veins, anterior and posterior, which unite in the common cardinal veins, from the body of the embryo. Thus three veins open into the right horn, and three into the left horn, of the sinus venosus (Fig. 270). Changes in the Vitelline and Umbilical Veins —Vena porte.—With the in- crease in size of the liver anlages there is an intercrescence of the hepatic cords and the endothelium of the vitelline veins. As a result, these veins form in the liver a network of sinusoids (Fig. 279), and each vein is divided into a distal portion which passes from the yolk sac to the liver, and into a proximal portion which DEVELOPMENT OF THE VEINS 269 carries blood from the liver sinusoids to the sinus venosus. The proximal portion of the left vitelline vein soon is largely absorbed into the sinusoids of the liver and shifts its blood flow into the right horn of the sinus venosus. In the mean- time the liver tissue grows laterally, comes into contact with the umbilical veins, and taps them so that their blood flows more directly to the heart through the sinusoids of the liver (Fig. 280). As the channel of the right proximal vitelline is larger, the blood from the left umbilical vein flows diagonally to the right horn of the sinus venosus. When all the umbilical blood enters the liver, as in embryos of Atrium. Common cardinal vein Left umbilical vein Sinusoids of liver. Left vitelline vein Right vitelline vein: Fic. 279.—Reconstruction of the blood vessels of a 4.2 mm. human embryo in ventral view (His). 5 to 6mm., the proximal portions of the umbilical veins atrophy and disappear (Fig. 281). In 5 mm. embryos the vitelline veins have formed three cross anas- tomoses with each other (Figs. 280 and 281): (1) a cranial transverse connec- tion in the liver, ventral to the duodenum; (2) a middle one, dorsal to the duode- num; and (3) a caudal one, ventral to it. There are thus formed about the gut a cranial and a caudal venous ring. In embryos of 7 mm. the left umbilical vein has enlarged, while the corresponding right vein has degenerated. Of the two venous loops, only the right limb of the cranial ring and the left limb of the 270 THE DEVELOPMENT OF THE VASCULAR SYSTEM caudal ring, together with the median dorsal anastomosis, persist. A new vein the superior mesenteric, develops in the mesentery of the intestinal loop and joins the left vitelline vein just caudal to its dorsal middle anastomosis with the right vitelline vein. Subsequently, with the atrophy of the yolk sac, the left vitelline vein degenerates caudal to its junction with the superior mesenteric vein. The persisting trunk between the superior mesenteric vein and the liver is the vena porte, and thus represents: (1) a portion of the left vitelline vein in the left limb of the caudal ring; (2) the middle transverse anastomosis between the vitelline veins; (3) the portion of the right vitelline vein which forms the right limb of the cranial ring. Ductus venosus v Left horn sinus venosus Right horn sinus venosus Left vitelline vein Cranial anastomosis of vitelline veins Middle anastomosis of vitelline veins Right umbilical vein Left umbilical vein Caudal anastomosis of vitelline veins Right vitelline vein Frc. 280.—Reconstruction of the veins of the liver in a 4.9 mm. human embryo (after Ingalls). In the liver the portal vein through its cranial anastomosis between the vitel- line veins is connected with the left umbilical vein. As the right lobe of the liver grows, the course of the umbilical and portal blood through the intrahepatit portion of the right vitelline vein becomes circuitous, and hence a new direct channel to the sinus venosus is formed through the hepatic sinusoids. This is the ductus venosus (Fig. 281), which is obliterated after birth and forms the ligamentum venosum of the postnatal liver. According to Mall, the intrahepatic portion of the right vitelline vein persists proxi- mally as the right ramus of the hepatic vein, and distally as the ramus arcuatus of the portal vein. The intrahepatic portion of the left vitelline vein drains secondarily into the right horn of the sinus venosus, and proximally forms later the /eft hepatic ramus. Distally, where it is connected with the left umbilical vein, it becomes the ramus angularis of the vena porte. In this way two primitive portal, or supplying trunks, and two hepatic, or draining trunks, \ DEVELOPMENT OF THE VEINS 271 originate. Later there are differentiated first four, then six, such opposed trunks within the liver, and the six primary lobules supplied and drained by these trunks may be recognized in the adult liver. Of the umbilical veins the right disappears early; the left persists during fetal life, shifts to the median line, and courses in the free edge of the falciform ligament. After birth its lumen is closed and from the umbilicus to the liver it forms the ligamentum teres. In early stages veins from the body wall drain into the umbilical veins. The Anterior Cardinal Veins and the Origin of the Superior Vena Cava.— The anterior cardinal veins consist each of two parts (Fig. 271): (1) The true anterior cardinals, located laterad in the segmented portion of the head and neck Efferent Common Ductus Efferent Portal vein fy Obliterated L. vitelline vein 4 enteric vein [ g ED Vitelli eo : Raahilizabien a a L. umbilical vein Fic. 281.—A diagram showing the development of the portal vein as illustrated ina human embryo of about 7 mm. (modified after His). and draining into the common cardinal veins; (2) the vena capitis medialis, ex- tending into the unsegmented head proper and running ventro-lateral to the brain wall. In embryos of 20 mm. there has formed by anastomosis a large con- nection between the right and left anterior cardinals, which carries the blood from the left side of the head into the right vein (Fig. 282 C). Soon the left anterior cardinal loses its connection with the common cardinal on the left side (Fig. 282 D). The proximal portion of the left common cardinal, with the trans- verse portion of the sinus venosus, persists as the coronary sinus. The right com- mon cardinal and the right anterior cardinal vein as far as its anastomosis with the left anterior cardinal become the superior vena cava. The anastomosis itself forms. the /eft vena anonyma, while that portion of the right anterior cardinal be- 272 THE DEVELOPMENT OF THE VASCULAR SYSTEM R. ant. cardinal vein- R. post. cardinal vein R. com. cardinal vein Inf. vena cava Mesonephros R. ischiadic vein R. ischiadic vein B cantieh ae Caudal vein Int. jugular vein L. vena anonyma Ext. jugular vein Ant. hemi- Subclavian vein azygos vein Azygos vein Sup. vena 298 cava Ext. jugular vein Int. jugular vein Subclavian vein Com. cardinal vein \V Coronary sinus aed O Inf. vena cava Hepatic vein Hemi-azygos vein 5 5 Post. card 7 = . card. “i eth R. suprarenal vein : Inf. vena , R. renal vein cava L. renal vein Post. cardinal _ A ) Spermatic veins Ext. iliac vein Com. iliac vein Hypogastric vein Cc Median sacral vein D Fic. 282.—Four diagrams showing the development of the superior and inferior vene cave and the fate of the cardinal veins (modified after Kollmann). X in A, anastomosis between hepatic and sub- cardinal vein; *, anastomosis between subcardinal veins; X in C, anastomosis between anterior car- dinal veins which forms the left vena anonyma; * in C, cranial anastomosis between the posterior car- dinal veins; z, caudal anastomosis between the same veins; A, kidney; S, suprarenal gland; T, testis. tween the left vena anonyma and the right subclavian vein is known as the right vena anonyma. The distal portions of the anterior cardinals become the internal DEVELOPMENT OF THE VEINS 273 jugular veins of the adult, while the external jugulars are new veins which develop somewhat later. The vena capitis medialis (Fig. 271) is the continuation of the anterior cardinal vein into the head of the embryo where at first it lies mesial to the cerebral nerves. Later itis partly shifted by anastomoses lateral to the cerebral nerves and forms the vena capitis lateralis (Figs. 283 and 284). In 11mm. embryos this emerges with the n. facialis, and, caudal to the n. hypoglossus, becomes the internal jugular. Cranially, in the region of the fifth nerve, the median vein of the head persists as the sinus cavernosus and receives the ophthalmic vein from the eye and the anterior cerebral vein from the fore- and mid-brain regions (Fig. 284 C). Between the n. trigeminus and the facialis, the middle cerebral vein from the metencephalon (cerebellum) joins the v. capitis lateralis before it leaves the cranium. More caudally the Middle cerebral vein Posterior cerebral vein : N. hypoglossus , V. capitis lateralis Sinus cavernosus—_\\ = Anterior cerebral vein iii Fic. 283.—Veins of the head of a 9 mm. human embryo (after Mall). x 9. posterior cerebral vein from the myelencephalon emerges through the jugular foramen and is drained with the others by the v. capitis lateralis into the internal jugular (Fig. 284 B). Soon the cerebral veins reach the dorsal median line (Fig. 284 C), and longitudinal anas- tomoses are formed: (1) between the anterior and middle cerebral veins, giving rise to the superior sagittal sinus; and (2) between the middle and posterior cerebral veins forming the greater part of the transverse sinuses. In embryos of 33 mm. the v. capitis lateralis disappears and the blood from the brain passes through the superior sagittal and lateral sinuses and is drained by way of the jugular foramen into the internal jugular vein (Fig. 284 C, D). The middle cerebral vein becomes the superior petrosal sinus, but the inferior petrosal sinus is formed as a new channel median to the internal ear. The anterior cerebral vein becomes the superficial middle cerebral of adult anatomy. A more detailed account of these changés may be found in the original work of Mall (Amer. Jour. Anat., vol. 4, 1905). 18 274 THE DEVELOPMENT OF THE VASCULAR SYSTEM The Posterior Cardinal Veins and the Origin of the Inferior Vena Cava.— The posterior cardinal veins course cephalad along the dorsal side of the meso- nephroi and open into the common cardinal veins (Fig. 282 A). Each receives an ischiadic vein from the posterior extremities, mesonephric branches from the mid-kidney and dorsal intersegmental veins from the body wall (Fig. 282 B). Median and ventral to the mesonephros are developed the subcardinal veins which are connected at intervals with the posterior cardinal veins by mesonephric sinu- soids, and with each other by anastomoses ventral to the aorta. Thus all the blood from the mesonephroi, posterior extremities, and dorsal body wall is in early stages drained by the posterior cardinal veins alone. The development of the unpaired vena cava inferior begins when communica- tion is established between the right hepatic vein of the liver and the right sub- cardinal vein of the mesonephros, primarily a tributary of the posterior cardinal vein (Lewis, 1902). The liver on the right side becomes attached to the dorsal body wall and from its point of union a ridge, the plica vene cave (Fig. 199), extends caudalward. According to Davis (1910), capillaries from the subcardinal vein invade the plica vene cave, and, growing cranially, meet and fuse with capillaries extending caudad from the liver sinusoids. Thus is formed the vein of the plica vene cave (Fig. 282 A), which is already present in human embryos of 2.6 mm. (Kollmann). This vein rapidly enlarges, as also do the sinusoidal connections between the subcardinals and posterior car- dinals at one point. Thus the blood from both lower posterior cardinals is soon carried to the heart, chiefly by way of the right subcardinal and right hepatic veins. (Fig. 282 B). Soon the posterior cardinals just cranial to their enlarged anasto- moses with the subcardinals become small and are interrupted (Fig. 282 C). Cranial to their interruption these veins communicate by a cross anastomosis. and were formerly believed to persist as the vv. azygos and hemiazygos of the adult. In the pig the posterior cardinal veins develop along the sides of the large mesonephroi and completely disappear with that organ. Sabin (Carnegie Publ. No. 223, 1915) has thus been able to confirm and extend the conclusion of Parker and Tozier that the vv. azygos and hemiazygos are entirely new veins derived from a. prevertebral capillary plexus. The more caudal portions of the posterior cardinal -veins likewise atrophy completely and are replaced by new prevertebral vessels. having essentially similar topographical relations. Caudal to their lowest trans- verse connection (z, Fig. 274 C), the new right vessel becomes the right common iliac DEVELOPMENT OF THE VEINS 275 vein: The corresponding portion of the new left vein with the transverse anas- tomosis. becomes the left common iliac vein. The blood from these veins is now drained by the unpaired inferior vena cava which is composed of the following veins: (1) the common hepatic and right hepatic veins (primitive right vitelline) ; (2) the vein of the plica vene cave; (3) an inter-renal portion of the right subcar- dinal vein with its great mesial anastomosis; (4) the new vein which replaces the right posterior cardinal. The permanent kidneys take up their positions opposite the great anastomosis between the subcardinals and at this point the renal veins are developed (Fig. A Confluence of the sinuses Middle cerebral vein Posterior cerebral Auditory vesicle i = aan, bs Superior Primitive jugular sagittal vein Vena capitis medialis Trigeminal nerve Ophthalmic vein sinus Superior sagit- ) tal sinus Vena capi- tis lateralis Vena ca pilis Anterior cerebral vein |_| | lateralis Ophthalmic vein | i ; Trigeminal nerve Auditory vesicle B D Anterior cerebral vein Inferior sagittal sinus Straight sinus Confluence of the Middle cerebral vein Sore ae Mpal 26k Confluence sinuses | Auditory vesicle Superior Sagittal SINUS of the sinuses Superior sagittal : sinus Posterior Superior pelrosal A SINUS | Trigeminal nerve DS Jugular Anterior cere- Trans- & vein bral vein verse O \phihalmic vein Vena capitis S ‘D henop ari- Sinus lateralis etal sinus ao"! . Auditory vesicle Ophthalmic vein | -Inf. petrosal sinus Trigeminal nerve Fic. 284.—Four diagrams showing the development of the veins of the head (after Mall). A, At four weeks; B, at five weeks; C, at the beginning of the third month; D, from an older fetus. 282 B); the longer left renal vein differs from the right in that proximally it rep- resents a left portion of the anastomosis itself (Fig. 282 D). A cephalic portion of the left subcardinal vein persists as the left suprarenal vein, which thus opens into the left renal instead of joining the inferior vena cava as does the right suprarenal vein of similar origin. The left spermatic or ovarian vein early drains into the-left caudal border of the great subcardinal anastomosis, which as we have seen contributes to the left renal vein. The right spermatic or ovarian vein opens into the right border of that portion of the subcardinal anastomosis which is in- 276 THE DEVELOPMENT OF THE VASCULAR SYSTEM corporated into the inférior vena cava. The /umoar veins develop from the same prevertebral plexus that gives rise to the caudal segment of the inferior vena cava. . Begg (Anat. Rec., vol. 10, 1916), on the contrary, finds that in the rat, where the meso- nephroi are diminutive, the posterior cardinal veins are not incorporated into the mesonephroi to disappear with that organ, but the right posterior cardinal persists as the segment of the inferior vena cava below the subcardinal contribution. A B = V. linguo-facialis V. linguo-facialis Dorsal subclavian vein, 4 . . kK 33— Ant. cardinal vein 4—Com. cardinal vein Dorsal subclavian vein Vena ulnaris prima Niwungiasss V .ulnaris prima oS V. thoraco-epigastrica Post. cardinal, vein V. thoraco- Ventral sub- epgastrica clavian vein V. jugularis interna V. linguo-facialis V. jugularis externa V. cephalica V Unnuo facials V. card. ant. V. jug. anterior V. anonyma V. card. com. dextra V. card post. a V. anonyma 7 Sinistra V. mammaria int, V. brachialis : Fic. 285.—Four reconstructions of the veins of the human right arm (after F. T. Lewis). > about 15. A, 10 mm. embryo; B, 11.5 mm. embryo; C, 16 mm. embryo; D, 22.8 mm. embryo. The Veins of the Extremities.—The primitive capillary plexus of the upper and lower - limb buds gives rise to a border vein (Figs. 285 and 321), which courses about the periphery of the flattened limb buds (Hochstetter). In the upper extremity, the ulnar portion of the border vein persists, forming at different points the subclavian, axillary, brachial, and basilic veins. The border vein at first opens into the dorsal wall of the posterior cardinal vein (em- bryos of 10 mm.), but, as the heart shifts its position caudalward, it finally drains by a ventral connection into the anterior cardinal or internal jugular vein (Lewis). The cephalic vein FETAL CIRCULATION 277 develops secondarily in connection with the ulnar border vein; later, in embryos of 23 mm., it anastomoses with the external jugular and finally drains into the axillary vein as in the adult. With the development of the digits, the vv. cephalica et basilica become distinct, as in embryos of 35 mm., but later are again connected by a plexus on the dorsum mani, as in the adult (Evans in Keibel and Mall, vol. 2). In the lower extremity the fibular portion of the primitive border vein persists. Later the v. saphena magna arises separately from the posterior cardinal, gives off the wv. femoralis and tibialis posterior, and annexes the fibular border vein at the level of the knee. Distal to this junction the border vein persists as the v. tibialis anterior and probably the v. saphena parva; proximally it becomes greatly reduced, forming the v. glutea inferior. Anomalies.—Anomalous blood vessels are of common occurrence. They may be due: (1) to the choice of unusual. paths in the primitive vascular plexuses; (2) to the persist- ence of vessels usually obliterated, e. g., double superior vene cave; right aortic arch; per- manent ductus arteriosus; (3) to incomplete development, e. g., double (unfused) heart or double dorsal aorte. FETAL CIRCULATION During fetal life oxygenated placental blood enters the embryo by way of the large umbilical vein and is conveyed to the liver (Fig. 286). There it mingles with the small amount of venous blood brought in by the portal vein. It is carried to the inferior vena cava either directly, through the ductus venosus, or indirectly through the liver sinusoids and hepatic vein. The impure blood of the inferior vena cava and portal vein affects but slightly the greater volume of pure placental blood. Entering the right atrium it mingles somewhat with the venous blood returned through the superior vena cava. It is said that the blood from the inferior vena cava is directed by the valve of this vein through the foramen ovale into the left atrium (following the path of the sounds in Figs. 262 to 264) which, before birth, receives little venous blood from the lungs. This purer blood of the left atrium enters the left ventricle, and is driven out through the aorta to be dis- tributed chiefly to the head and upper extremities. The venous blood of the superior vena cava, slightly mixed, is supposed to pass from the right atrium into the right ventricle, whence it passes out by the pulmonary artery. A small amount of this blood is conveyed to the lungs by the pulmonary arteries, but, as the fetal lungs do not function, most of it enters the dorsal aorta by way of the ductus arteriosus. Since the ductus is caudal to the origin of the subclavian and carotid arteries, its less pure blood is distributed to the trunk, viscera, and lower extremities. The placental circuit is completed by the hypogastric, or umbilical, arteries by way of the umbilical cord. Pohlman (Anat. Rec., vol. 2, 1908) interprets ..s experiments to indicate that, con- trary to the generally accepted view, there is a mingling of the blood which enters the right atrium through the two caval veins. If this occurs there would be no difference in the quality of blood distributed to the various parts of the body. 278 THE DEVELOPMENT OF THE VASCULAR SYSTEM Changes at Birth.—At birth the umbilical vessels are ruptured and the lungs become functional. The umbilical arteries and veins, no longer used, contract Fic. 286.—Diagrammatic outline of the organs of circulation in the fetus of six months (Allen Thomson).! RA, Right atrium of the heart; RV, right ventricle; LA, left atrium; Eo, valve of inf. vena cava; LV, left ventricle; L, liver; K, left kidney; J, small intestine; a, arch of the aorta; a’, its dorsal part; a’’, lower end; vcs, superior vena cava; vci, inferior vena cava where it joins the right atrium; zw?" its lower end; s, subclavian vessels; j, right jugular vein; c, common carotid arteries; four curved dotted arrow lines are carried through the aortic and pulmonary opening and the atrio-ventricular orifices; da, opposite to the one passing through the pulmonary artery, marks the place of the ductus arteriosus; a similar arrow line is shown passing from the vena cava inferior through the fossa ovalis of the right atrium and the foramen ovale into the left atrium; /v, the hepatic veins; »p, vena porte; x to vci, the duc- tus venosus; #v, umbilical vein; va, umbilical arteries; «c, umbilical cord cut short; 7, i’, iliac vessels. and their lumina are obliterated by the thickening of the inner coat (tunica in- tima). The lumen of the umbilical artery is occluded after four days, that of 1Jn this diagram the arteries are conventionally colored red and the veins blue, but these colors are not intended to indicate the nature of the blood conveyed by the respective vessels. THE LYMPHATIC SYSTEM 279 the umbilical vein within a week. The cord-like vein is persistent as the liga- mentum teres of the liver; the arteries become the obliterated hypogastrics. The ductus venosus atrophies because after birth only the blood from the por- tal vein enters the liver, and this is all drained into the liver sinusoids, forming the portal circulation. The ductus venosus is persistent as the fibrous ligamentum venosum, embedded in the wall of the liver. The ductus arteriosus ceases to function after birth, as all the blood from the pulmonary arterial trunk is conveyed to the expanded lungs. The ductus be- comes impervious from ten to twenty days after birth and persists as a solid, fibrous cord, the ligamentum arteriosum. After birth, the large amount of blood now returned to the left atrium from the functional lungs equalizes the pressure in the two atria. Asa result, both dur- ing diastole and systole, the septum primum, or valve of the foramen ovale, is pressed against the septum secundum, closing the foramen ovale. Eventually the two septa fuse, though they may be incompletely united during the first year after birth, or even longer (p. 255). ~™ ‘THE LYMPHATIC SYSTEM The lymphatic system originates in a plexus of lymphatic capillaries distrib- uted along the primitive main venous trunks. By the dilation and coalescence of this network at definite regions five lymph sacs appear (Fig. 287). Paired jugular sacs arise in 10 to 11 mm. embryos lateral to the internal jugular veins. In embryos of 23 mm. the unpaired retroperitoneal sac develops at the root of the mesentery adjacent to the suprarenal bodies, and the cisterna chyli also appears. Paired posterior sacs arise in relation to the sciatic veins in embryos 24 mm. long. These sacs at first contain blood which they soon discharge into neighboring veins, thereupon losing their venous connections. With relation to the lymph sacs as centers, the thoracic duct (at 30 mm.) and the peripheral lymphatics develop. The jugular sacs alone acquire with the internal jugular veins secondary con- nections which are later utilized by the thoracic and right lymphatic ducts. The various sacs themselves are eventually transformed into chains of lymph nodes. Two discordant views exist as to the origin of the lymphatics. According to Sabin (Amer. Jour. Anat., vols. 1, 1901; 9, 1909) and Lewis (Amer. Jour, Anat., vol. 5, 1906), sprouts arising from the endothelium of veins form the single and paired sacs already described. From these five sacs the thoracic duct and peripheral lymphatics develop as endothelial outgrowths. Thus lymphatic vessels grow to the head, neck, and arm from the jugular sacs; to the hip, back, and leg from the 280 THE DEVELOPMENT OF THE VASCULAR SYSTEM posterior sacs; and to the mesentery from the retroperitoneal sac. According to this view, then, endothelium can arise only from pre-existing endothelium. Other investigators (Huntington, Amer. Jour. Anat., vol. 16, 1914; Mem. Wistar Inst., 1911; and McClure) hold that the lymph sacs are formed in situ by the fusion of discrete mesenchymal spaces which become lined with an endothe- Fic. 287.—Flat reconstruction of the primitive lymphatic system in a human embryo 30 mm. long (Sabin). X about 3.5. C.c., Cisterna chyli; Lg., lymph gland; S.J.jug., jugular lymph sac; S.l.mes., retroperitoneal lymph sac; S./.p., posterior lymph sac; S./.s., subclavian lymph sac; V.c., cephalic vein; V.c.i., inferior vena cava; V.f., femoral vein; V.j.7., internal jugular vein; V/I.p., deep lymphatics; V.l.s., superficial lymphatics; V.r., renal vein; V.s., sciatic vein; V.w.(p.), primi- tive ulnar vein. lium of transformed, bordering mesenchymal cells. Venous connections are purely secondary. The thoracic duct and the peripheral vessels develop similarly by the progressive fusion of separate clefts; hence endothelium can differentiate continually from young mesenchyma. The further growth of endothelium, already formed, is not denied. A Afferent lyinphatic vessels “A=. Pewee of Peripheral lymph sinus Network of lymphatic. eripnerat Lymph st vessels — Capsule ‘— Trabecula Reticular tissue cells Lym phatic vessel Blood vessels Lymphatic vessel B Afferent lymphatic vessels ee A Se — » : Peripheral sinus iad 6 Secondary nodule Pes fa eee Lymph sinus a ‘Si Medullary cord Capsule’ Ox Trabecula Efferent lymphatic vessels Fic. 289.—Diagrams representing four stages in the development of lymph glands. The earlier stages : are shown on the left side of each figure (Lewis and Stohr). THE LYMPHATIC SYSTEM 281 Rapidly accumulating evidence seems to favor the latter view. The method of injection, upon which Miss Sabin and her followers have largely relied, has its limitations, for it obviously can furnish no information regarding discrete spaces prior to their linkage into continuous channels. Concise summaries of these views are given by Sabin (Anat. Rec., vol. 5, 1911) and by McClure (Anat. Rec., vols. 5, 1912; 9, 1915). Lymph Glands.—Paired lymph glands appear during the third month, first in the axillary, iliac, and maxillary regions. Those from the lymph sacs develop later. Plexuses of lymphatics first form either as ordinary networks of peripheral vessels or as secondary networks produced by a connective tissue invasion of the primitive lymph sacs. In either case a capillary plexus, with simple connective ay -- M esogastrium : yw --Spleen anlage A B Fic. 288.—Two stages in the early development of the human spleen (dorsal is below). A, from an em- bryo of 10.5 mm. (Kollmann); B, from a 20 mm. embryo (Tonkoff). tissue septa, marks the first stage of development. Next (Fig. 289 A), lympho- cytes collect in the connective tissue, forming follicles which become associated with blood capillaries. Finally, the lymphoid tissue is channeled by sinuses formed from lymphatic capillaries. The peripheral sinus develops afferent and efferent vessels. The central sinuses cut the lymphoid tissue into cords. In the larger lymph glands (Fig. 289 B) the connective tissue forms a definite capsule from which trabecule dip into the gland. Hemolymph glands, according to Schumacher (Arch. f. mik. Anat., Bd. 81, 1912), begin their development like lymph glands, but soon after the formation of the peripheral sinus the lymphatic connections degenerate and blood escapes from the blood capillaries into what are henceforth blood sinuses. Spleen.—This appears in embryos of about 10 mm. as a swelling on the left 282 THE DEVELOPMENT OF THE VASCULAR SYSTEM side of the dorsal mesogastrium near the dorsal pancreas (Fig. 288 A). The thickening is due to a temporary proliferation and invasion of mesothelial cells into the underlying mesenchyme, which, meanwhile, has also undergone local enlargement and vascularization. Contrary to the older view, the cells from the peritoneal epithelium probably give rise to a large part, if not all, of the future spleen. The splenic anlage becomes pinched off from the mesogastrium (Fig. 288 B) with which it is ultimately joined by a narrow band only. At first the blood vessels constitute a closed system. The peculiar adult circulation is acquired relatively late. Lifschitz has shown that, in human fetuses between 150 and 300 mm. long, red blood cells are actively formed in the splenic pulp as clusters around the giant cells. The lymphoid tissue of the spleen first appears as ellipsoids about the smallest arteries in fetuses of four months. At seven months the ovoid splenic corpuscles appear as lymphoid nodules about the larger arteries. Glomus Coccygeum.—The coccygeal gland is present in 150 mm. (C H) fetuses as an encapsulated cluster of polyhedral cells at the apex of the coccyx. Later it becomes lobulated by the ingrowth of connective tissue trabecule and receives a rich vascular supply. According to Stoerck (1906) its tissue at no time resembles the chromaffin bodies, although this has commonly been believed. CHAPTER X HISTOGENESIS THE primitive cells of the embryo are alike in structure. The protoplasm of each exhibits the fundamental properties of irritability, contractility, reproduc- tion, and metabolism (the absorption, digestion, and assimilation of nutritive sub- stances and the excretion of waste products, processes through which growth and reproduction are made possible). As development proceeds, there is a gradual differentiation of the cells into tissues, each tissue being composed of like cells, the structure of which has been adapted to the performance of a certain special function. In other words, there is division of labor and adaptation of cell structure to the function which each cell performs. The differentiation of tissue cells from the primitive cells of the embryo is known as histogenesis. On page 54 the derivatives of the germ layers are given. We shall take up briefly the histo- genesis of the tissues derived from the entoderm, mesoderm, and ectoderm in the order named. THE HISTOGENESIS OF THE ENTODERMAL EPITHELIUM The cells of the entoderm are little modified from their primitive structure. From the first they are concerned with the processes of absorption, digestion, assimilation, and excretion. They form always epithelial layers, lining the di- gestive and respiratory canals and the glandular derivatives of these. In the pharynx, esophagus, and trachea the cells are early of columnar form and ciliated. The epithelium of the pharynx and esophagus becomes stratified and the surface layers flatten to form squamous cells. The stratified epithelium is developed from a basal germinal layer like the epidermis of the integument (see p. 294). Throughout the rest of the digestive canal the simple columnar epithelium of the embryo persists. At the free ends of the majority of the cells a cuticular mem- brane develops. Other cells are converted into unicellular mucous glands or goblet cells. As outgrowths of the intestinal epithelium, are developed the simple tu- bular glands of the stomach and intestine, and the liver and pancreas. In the respiratory tract the entoderm forms at first a simple columnar epi- thelium. Later, in the trachea and bronchi this is differentiated into a pseudo- stratified, ciliated epithelium. The columnar epithelium of the alveoli and alveo- 283 284 HISTOGENESIS lar ducts of the lungs is converted into the flattened respiratory epithelium. The development of the thymus and thyreoid glands, liver and pancreas has been described in Chapter VII. HISTOGENESIS OF THE MESODERMAL ‘TISSUES The differentiation of the mesoderm has been described on p. 51, Fig. 53. It gives rise to the mesodermal segments, intermediate cell masses, somatic and splanchnic layers, all of which are epithelia, and to the diffuse mesenchyme. The somatic and splanchnic layers of the mesoderm form on their coelomic surfaces a single layer of squamous cells termed the mesothelium. This is the covering layer Mesodermal segment Central cells of segment Intermediate cell mass Urogenital ridge. - Somatic mesoderm Splanchnic mesoderm 3 4 Hy Splanchnic ee a og mesoderm _ Fic. 290.—Transverse section of a 4.5 mm. human embryo showing the development of the sclerotomes (Kollmann). X about 300. of the pericardium, pleure, peritoneum, mesenteries, serous layer of the viscera, and lining of the vaginal sac in the scrotum. From this mesothelium is derived the spleen and also the epithelia of the genital glands and the Miillerian ducts. The intermediate cell masses or nephrotomes are the anlages of the pro- nephros, mesonephros, metanephros, and their ducts (p. 195). The Sclerotomes and Mesenchyme.—The cavities of the mesodermal seg- ments become filled with diffuse, spindle-shaped cells derived from the adjacent walls; their median walls are next converted into similar tissue and the whole migrates mesially towards the neural tube and notochord, and eventually sur- rounds these structures (Figs. 290 and 323). This diffuse tissue is mesenchyme (see p. 53), and that derived from a single mesodermal segment constitutes a sclerotome. THE SUPPORTING TISSUES 285 The sclerotomes ultimately are converted into connective tissue, into the ver- tebre, and into the basal portion of the cranium. The persisting lateral plate of the mesodermal segment becomes a dermo-myotome, from which the voluntary muscle is differentiated and probably the corium of the integument. In the head region, cranial to the otocysts, no mesodermal segments are formed, but the primitive mesoderm is converted directly into mesenchyme. Mesenchyme is derived also from the somatic and splanchnic mesoderm and from the primitive streak tissue. From the mesenchyme a number of tissues are developed (see p. 54). The origin of the blood and primitive blood vessels and lymphatics has been described; it remains to trace the development of the sup- porting tissues (connective tissue, fat, cartilage, and bone) and of the muscle fibers. THE SUPPORTING TISSUES The supporting tissues are peculiar in that during their development from the mesenchyme a fibrous, hyaline, or calcified matrix is formed which becomes greater in amount than the persisting cellular elements of the tissue. Connective Tissue.—Different views are held as to the differentiation of con- nective tissue fibers. According to Laguess and Merkel, the fibers arise in an intercellular matrix derived from the cytoplasm of mesenchymal cells. Szily holds that fibers are first formed as processes of epithelial cells and that into this fibrous network mesenchymal cells later migrate. The view generally accepted, that of Fleming, Mall, Spalteholz, and Meves, is that the primitive connective tissue fibers are developed as part of the cell, z. e., are zntracellular in origin. The mésenchyme is at first compact, the cell nuclei predominating. Soon a syncytium is developed, the cytoplasm increasing in amount and forming an open network. Next the cytoplasm is differentiated into a perinuclear granular endoplasm and an outer distinct hyaline layer of ectoplasm (Fig. 291 A) (Mall, Amer. Jour. Anat., vol. 1, 1902). In the ectoplasm fibrils appear, derived from coarse filaments known as chondrioconta (Meves, 1910). Reticular Tissue.—Fine fibers arise in the ectoplasm of the mesenchymal syncytium. The nuclei and endoplasm persist as reticular cells. According to Mall, reticular fibers differ chemically from white connective tissue fibers. White Fibrous Connective Tissue.—The differentiation of this tissue may be divided into two stages: (1) a prefibrous stage during which the ectoplasm is formed rapidly by the endoplasm of the cells, and fibrils resembling those of reticular tissue appear in the ectoplasm (Fig. 291 A); (2) the anastomosing fibers take the form of parallel bundles and are converted through a chemical change 286 Fibrille in ectoplasmic matrix Cell of syncytium Elastic fiber HISTOGENESIS Cc Mesenchymal cell Cartilage matrix Cartilage cell Fic. 291.—The differentiation of the supporting tissues (after Mall). 270. 4, White fibers forming in the corium of a 5 cm. pig embryo; B, elastic fibers forming in the syncytium of the umbilical cord from a 7 cm. embryo; C, developing cartilage from the occipital bone of a 20 mm. pig embryo. into typical white fibers. The spindle-shaped cells are transformed into the connective tissue cells characteristic of the adult. In tendons, the bundles of Fic. 292.—Develop- ing fat cells, the fat black- ened with osmic acid (after Ranvier). n., Nucleus; g., fat globules. é plasmic granules, but white fibers are arranged in compact parallel fascicles, in areolar tissue they are interwoven to form a meshwork. The cells of the tendons are compressed between the bundles of fibers and this accounts for their peculiar form and arrangement. In the cornea of the eye the cells retain their processes. The corneal tissue is thus embryonic in character and is without elastic fibers or blood vessels. Elastic Tissue.—With the exception of the cornea and tendon, yellow elastic fibers develop in connection with all white fibrous connective tissue. Like the white fibers they are produced in the ectoplasm of the mesenchymal syncytium (Fig. 291 B). They are de- veloped as single fibers, but may coalesce to form the fenestrated membranes of the arteries. According to Ranvier, elastic fibers are produced by the union of ecto- this view is not supported by either Mall or Spalteholz. CARTILAGE 2847 Adipose Tissue.—Certain of the mesenchymal cells give rise not to fibro- blasts but to fat cells. They secrete within their cytoplasm droplets of fat which increase in size and become confluent (Fig. 292). Finally, a single fat globule fills the cell of which the nucleus-and cytoplasm are pressed to the periphery. The fat cells are most numerous along the course of the blood vessels in areolar con- nective tissue and appear first during the fourth month. CARTILAGE Cartilage has been described as developing in two ways: (1) The mesen- chymal cells increase in size and form a compact cellular precartilage. Later the hyaline matrix is developed be- tween the cells from their cyto- ‘ plasm (Fig. 293 A). The matrix may in this case be regarded as Precartilage Cartilage -- 5 ONY cise the ectoplasm of the cartilage cells. (2) According‘to Mall, mes- enchymal cells give rise first to an ectoplasm in which fibrille de- velop. Next, the cells increase in size and are gradually extruded Fic. 293.—Diagrams of the development of car- until they lie in the spaces of the _ tilage from mesenchyma (Lewis and Stéhr). A, Based upon Studnicka’s studies of fish; B, upon Mall’s study of mammals. Mes., mesenchyma. ectoplasmic matrix (Figs. 291 C and 293 B). Simultaneously, the ectoplasm is converted into the hyaline matrix peculiar to cartilage, undergoing both a chemical and structural change. About the cartilage cells the endo- plasm produces capsules of hyaline substance. The interstitial growth of cartilage is due: (1) to the direct production of new hyaline matrix; (2) to the formation of capsules about the cells and their transformation into mattix; (3) to the proliferation of the cartilage cells, which may separate or occur iri clusters within a single capsule. ‘ Perichondral growth also takes place about the periphery of the cartilage and is due to the activity of persisting mesenchymal cells, which, with an outer sheath of connective tissue, constitute the perichondrium. When cartilage is replaced by bone the perichondrium becomes the periosteum. In hyaline cartilage the matrix remains hyaline. In fibro-cartilage the fibrillations of the primitive ectoplasm are converted into white fibers. In elastic cartilage yellow elastic fibers are formed in the hyaline matrix, according to Mall; before the hyaline matrix is differentiated, according to Spalteholz. Most of the bones of the skeleton are laid down first in the form of cartilage. Later, this is gradually replaced by the development of bone tissue. 288 HISTOGENESIS BONE Bone is a tissue appearing relatively late in the embryo. There are de- veloped two types, the membrane bones of the face and cranium and the cartilage bones which replace the cartilaginous skeleton. Cartilage bones are not simply cartilage transformed into bone by the deposition of calcium salts, but represent a new tissue which is developed as the cartilage is destroyed. Membrane Bone.—The flat bones of the face and skull are not preformed as cartilage. The form of a membrane bone is determined by the development of a Osteoblast A Bone matrix\ Katharine Wilh Bone cell Bone Osteoclast Fibrille in bone matrix Fic. 294.—Two stages in the development of bone. A, Section through the frontal bone of a 20 mm. pig embryo (after Mall). > 270. B, Section through the periosteum and bone lamelle of the mandible of a 65 mm. human fetus. X 325. periosteal membrane from the mesenchyma. ‘The bone matrix is differentiated within the periosteum from enlarged cells, the osteoblasts (bone formers). Osteo- blasts appear in clusters and from their cytoplasm is differentiated a fibrillated ectoplasmic matrix like that which precedes the formation of connective tissue and cartilage (Fig. 294 A). This fibrillated matrix, by a chemical change apparently, is converted into a homogeneous bone matrix, which first takes the form of spicules. Others view the fibrillated matrix as an intercellular product and the bone matrix as an interfibrillar deposit. Howéver this may be, the spicules Fic. 295.—A longitudinal section of the two distal phalanges from the finger of a five-months’ hu- man fetus (Sobotta). XX 15. Kn, Cartilage showing calcification and resorption; eK, endochrondral bone; M, marrow cavity; pK, periosteal bone. BONE 289 coalesce, form a network of bony plates, and constitute the bone matrix upon the surfaces of which osteoblasts are arranged in a single layer like the cells of an epithelium (Fig. 294 B). These cells may be cuboidal, columnar, or may flatten out as bone formation ceases. As the matrix of the bone is laid down, osteoblasts Lecome engulfed and form bone cells. The bone cells are lodged in spaces termed lacune. These are connected by microscopic canals, the canaliculi, in which delicate cell processes course and anastomose with those of neighboring cells. The plates of the spongy membrane bone are formed about blood vessels as centers. As the bone grows at the periphery, the bone matrix is resorbed centrally. At this time large multinucleated cells (43 to 91 « long) appear upon the surfaces of the bone matrix. These cells are known as osteoclasts (bone destroyers). There is, however, no positive evidence that the osteoclasts are active in dissolving the bone. They may be interpreted also as degenerating, fused osteoblasts (Arey, Anat. Rec., vol. 11, 1917). The cavities in which they are frequently lodged are known as Howship’s lacune. The bone lamelle of the cen- tral portion of the membrane bone are gradually resorbed and this portion of the bone is of a spongy texture. Some time after birth, compact bone lamella are laid down by the inner osteoblast cells of the periosteum. In the case of flat bones, compact inner and outer plates or tables are thus developed with spongy bone between them. The spaces in the spongy bone are filled by derivatives of the mesenchyme: reticular tissue, blood vessels, fat cells, and developing blood cells. These together constitute the red bone marrow. The ossification of mem- brane bone begins at the middle of the bone and proceeds in all directions from this primary center. Cartilage Bone.—The form of the cartilage bone is determined by the pre- formed cartilage and its surrounding membrane, the perichondrium (Fig. 296). Bone tissue is developed as in membrane bones, save that the cartilage is first destroyed and the new bone tissue develops (1) in, and (2) about it. In the first case, the process is known as endochondral bone formation. In the second case, it is known as perichondral or periosteal bone formation. Endochondral Bone Formation.—The cartilage cells enlarge, become ar- ranged in characteristic rows, and lime is deposited in the matrix (Fig. 295). The perichondrium becomes the periosteum. From its inner or osteogenic layer, which is densely cellular, ingrowths invade and resorb the cartilage and fill the primary marrow cavities. The invading osteogenic tissue gives rise to osteoblasts and bone marrow. By the osteoblasts bone is differentiated directly upon persisting portions of the cartilage. As new bone is developed peripherally, it is 19 290 HISTOGENESIS resorbed centrally to form large marrow spaces. Eventually, all of the cartilage matrix, and probably the cartilage cells as well, are destroyed. Perichondral Ossification——Compact bone is developed after birth by the osteogenic layer of the periosteum and thus are produced the periosteal lamelle. In the ribs this is said to be the only method of ossification. The bone lamelle deposited about a blood vessel are concentrically arranged and form the concentric lamelle of a Haversian system. The Haversian canal of adult bone is merely the space occupied by a blood vessel. Growth of Cartilage Bones.—In cartilage bones there is no interstitial growth as in cartilage. Most of the cartilage bones have more than one center of ossi- fication and growth is due to the expansion of the interven- ing cartilage. Flat bones grow at the periphery; ring like bones, such as the vertebre, have three primary centers of ossification, between which the cartilage continues to grow (Fig. 296 A). In the case of the numerous long bones of the skeleton, the primitive ossi- fication center forms the shaft or diaphysis (Fig. 296 C-F). The cartilage at either end of the diaphysis grows rapidly and thus the bone increases Frc. 296.—Diagrams to show the method of growth of in length. Eventually, osteo- A, a vertebra; B, of sacrum; C-F, of a long bone (the 2 genic tissue invades these car- tibia). tilages and new ossification centers, the epiphyses, are formed, one at either end. When the growth of the bone in length is completed, the epiphyses, by the ossification of the intervening cartilage, are united to the diaphysis. The shaft of the long bones grows in diameter by the peripheral deposition of bone lamella and the central resorption of the bone. In the larger long bones spongy, or cancellated, bone tissue persists at the ends, but in the middle portion a large medullary, or marrow cavity, is developed. This is filled chiefly with fat cells and constitutes the yellow bone marrow. THE HISTOGENESIS OF MUSCLE 2g1 Regeneration of Bone.—If bone is injured or fractured, new bone is developed by osteoblasts derived either from the periosteum or from the bone marrow. The repair of a fracture is usually preceded by the formation of cartilage which unites the ends of the bones and is later changed to bone. In adults, the periosteum is regarded as especially important in the regeneration of bone tissue. Macewen (1912), however, rejects this view. Joints.—In joints of the synarthrosis type in which little movement is allowed the mesenchyma between the ends of the bones differentiates into connective tissue or cartilage. This persists in the adult. In joints of the dzarthrosis type the bones are freely movable. The mesen- chyma between the bones develops into an open connective tissue in which a cleft appears, the joint cavity. The cells lining this cavity flatten out and form a more or less continuous layer of epithelium, the synovial membrane. From the con- nective tissue surrounding the joint cavity are developed the various fibrous ligaments typical of the different joints. Ligaments or tendons apparently cours- ing through the adult joint cavities represent secondary invasions, which are covered with reflexed synovial membrane, and hence are really external to the cavity. THE HISTOGENESIS OF MUSCLE The muscular system is composed of muscle fibers which form a tissue in which contractility has become the predominating function. The fibers are of three types: (1) smooth muscle cells found principally in the walls of the viscera and blood vessels; (2) striated skeletal muscle, chiefly attached to the elements of the skeleton and producing voluntary movements; (3) striated cardiac muscle, form- ing the myocardium of the heart. All three types are derived from the meso- derm. The only exceptions are the smooth muscle of the iris, and the smooth muscle of the sweat glands, which are derived from the ectoderm. Smooth Muscle in general may be said to arise from the mesenchyme, or from embryonal connective tissue. Its development has been studied by McGill (Internat. Monatschr. f. Anat. u. Physiol., vol. 24, 1907) in the esophagus of pig embryos. The stellate cells of the mesenchyma enlarge, elongate, and their cytoplasm becomes more abundant. The resulting spindle-shaped cells remain attached to each other by cytoplasmic bridges and develop in the superficial layer of their cytoplasm coarse non-contractile myoglia fibrils (Fig. 297) similar to the primitive fibrille of connective tissue. The myoglia fibrils may extend from cell to cell, thus connecting them. These fibrils are the products of coa- lesced granules found within the cytoplasm of the myoblasts. In embryos of 30 mm. fine myofibrille are differentiated in the cytoplasm of the myoblasts 292 HISTOGENESIS and give it a longitudinally striated appearance. The cytoplasmic processes of the muscle cells, the cytoplasmic bridges, later give rise to white connective tissue fibers which envelop the muscle fibers and bind them together. Smooth muscle increases in amount: (1) by the formation of new fibers from the mesen- chyme of the embryo; (2) by the transformation into muscle fibers of interstitial Fic. 297.—Two stages in the development of smooth muscle fibers (after McGill). A, from the esophagus of a 13 mm. pig (X 550); coalescing granules give rise to coarse myoglia fibrils. B, from the esophagus of a 27 mm. pig (X 850); both coarse myoglia fibrils and fine myofibrils are present. cells; (3) by the multiplication of their nuclei by mitosis in the more advanced fetal stages. Striated Skeletal Muscle.—All striated voluntary muscle is derived from the mesoderm, either from the myotomes of the segments (muscles of the trunk) or from the mesenchyma (muscles of the head). According to Bardeen (in Keibel and Mall, vol. 1), after the formation of the sclerotome (Fig. 290), which Fic. 298.—Stages in the histogenesis of skeletal muscle (after Godlewski). A, from 13 mm. sheep embryo; B, homogeneous myofibrils in myoblast from 10 mm. guinea pig embryo; C, myoblast from 8.5 mm. rabbit embryo with longitudinally splitting striated myofibrils. gives rise to skeletal tissue, the remaining portion of the primitive segment con- stitutes the myotome. All the cells of the myotome give rise to myoblasts. Wil- liams (Amer. Jour. Anat., vol. 11, 1910), working on the mesodermal segments of the chick, finds that only the dorsal and mesial cells are myoblasts. By multi- plication they form a mesial myotome, while the lateral cells of the original THE HISTOGENESIS OF MUSCLE 293 mesodermal segment persist as a dermatome and give rise only to the connective tissue of the corium (Fig. 323). The dermatome lies lateral to the myotome (Fig. 47) and the two together constitute the dermo-myotome (Williams). As to the origin of the striated voluntary muscle fibers, there is also a differ- ence of opinion. It is generally believed that the myoblasts elongate, and, by the repeated mitotic division of their nuclei, become multinucleated. (God- lewski, however, holds that several myoblasts unite to form a single muscle fiber.) The nuclei lie at first centrally, surrounded by the granular sarcoplasm (Fig. 298 A). The sarcoplasmic granules become arranged in rows and constitute the myofibrille which increase in number by longitudinal splitting (Fig. 298 B, C). The myofibrille soon differentiate alternating dark and light bands, due to differ- ences in density, and the individual fibrilla become so grouped that their dark and light bands coincide (Fig. 298 C). During development the muscle fibers increase enormously in size, the nuclei migrate to the surface, and the myofibrille are arranged in bundles or muscle columns (sarcostyles). The fibrils of each col- umn are said to arise by the longitudinal splitting of single primitive myofibrils. According to Baldwin (Zeitschr. f. allg. Physiol., vol. 14, 1912), the nucleus and perinu- clear sarcoplasm is separated from the rest of the muscle fiber by the sarcolemma. With Apathy, he would therefore regard the myofibrille as a differentiated product of the muscle cells and to be homologized with connective tissue fibers. The extrusion of the muscle cell from the muscle fiber may be compared to the extrusion of cartilage cells from the pre- cartilage matrix, as described by Mall (see p. 287). During the later stages in the development of striated voluntary muscle there is, accord- ing to many observers, an active degeneration of the muscle fibers. While smooth muscle fibers form a syncytium and the enveloping connective tissue is developed directly from the muscle cells, in the case of striated skeletal muscle each fiber is a multinucleated entity which is bound together with others by connective tissue of independent origin. Striated Cardiac Muscle.—This is developed from the splanchnic mesoderm which forms both the epicardium and the myocardium (Fig. 255). The cells of the myocardium at first form a syncytium in which myofibrille develop from chondrioconta, or cytoplasmic granules. The myofibrille are developed at the periphery of the syncytial strands of cytoplasm and extend long distances in the syncytium. They multiply rapidly and form dark and light bands as in skeletal muscle. The syncytial character of cardiac muscle persists in the adult and the nuclei remain central in position. The intercalated discs, typical of adult cardiac muscle, appear relatively late, just before birth in the guinea pig (Jordan and Steele, 1912). 2904 HISTOGENESIS ‘THE HISTOGENESIS OF THE ECTODERMAL DERIVATIVES Besides forming the enamel of the teeth and the salivary glands (cf. p. 161), the ectoderm gives rise: (1) to the epidermis and its derivatives (subcutaneous glands, nails, hair, and the lens and conjunctiva of the eye); (2) to the nervous sys- tem and sensory epithelia; (3) to parts of certain glands producing internal secre- tions such as the pituitary body, suprarenal glands, and chromaffin bodies. We shall describe here the histogenesis of the epidermis, the development of its derivatives, and the histogenesis of the nervous tissues, reserving for final chap- ters the development of the nervous organs and the glands formed in part from them. THE EPIDERMIS The single-layered ectoderm of the early embryo by the division of its cells becomes differentiated into a two-layered epidermis composed of an inner layer of cuboidal or columnar cells, the stratum germinativum, and an outer layer of flattened cells, the epitrichium or periderm (Fig. 299 A). The stratum germinativum is the reproducing layer of the epidermis. As development proceeds, its cells by division gradually give rise to new layers above it until the epidermis becomes a many-layered or stratified epithelium. The periderm is always the outermost layer of the epidermis. In embryos of 25 to 121 mm. (C R) the epidermis is typically three-layered, the outer flattened layer forming the periderm, a middle layer of polygonai cells, the intermediate layer, and the inner columnar layer, the stratum germinativum (Fig. 299 B). After the fourth month the epidermis becomes many layered. The inner layers of cells now form the stratum germinativum and are actively dividing cells united with each other by cytoplasmic bridges. The outer layers of cells become cornified, the cornification of the cells proceeding from the stratum germinativum toward the surface. Thus, next the germinal layer are cells containing keratohyalin, which constitute the double-layered stratum granulosum. A thicker layer above the stratum granulosum shows cells in which drops of a substance called eleidin are formed. These droplets, which are supposed to represent softened keratohyalin, give these cells a clear appearance when examined unstained. Hence the layer is termed the stratum lucidum. In the outer layers of the epidermis the thickened walls of the cells become cornified and in the cells themselves a fatty substance collects. These layers of cells constitute the stratum corneum. The cells of this layer are also greatly flattened, especially at the surface. When the hairs develop they do not penetrate the outer periderm layer of the epidermis, but, as they grow out, lift it off (sixth month). Hence this layer THE HAIR 205 is known also as the epitrichium (layer upon the hair). Desquamated epitrichial and epidermal cells mix with the secretion of the sebaceous glands to form the cheesy vernix caseosa which covers the fetal skin. Pigment granules appear soon after birth in the cells of the stratum germinativum. ‘These granules are prob- ably formed im situ. Negro children are quite light in color at birth, but within six weeks their integument has reached the normal degree of pigmentation. The derma or cortum of the integument is developed from mesenchyme, perhaps from that of the dermatomes (Fig. 323) of the mesodermal segments (p. 292). At about the end of the third month a differentiation into the compact Epitrichium =e pec = ae % 2 @ —S= SSS = Sore Se oS S Saye Corium = Se See = Beas SS <8 oS Ss se = 2S SSS SS rt Stratum germinatioum—= Epitrichium Intermediate layer Stratum germinativum = =~ es ae Wa oS ie =e Hi Fic. 299.—Sections of the integument from a 65 mm. human fetus. > 440. A, Section through the integument of the neck showing a two-layered epidermis and the beginning of a third intermediate layer; B, section from the integument of the chin in which three layers are well developed in the epidermis. corium proper and the areolar subcutaneous tissue occurs. From the corium papille project into the stratum germinativum. Anomalies.—Dermoid cysts, resulting from epidermal inclusions, are not infrequent along the lines of fusion of embryonic structures, e. g., branchial clefts, mid-dorsal and mid- ventral body wall. THE HAIR Hairs are derived from thickenings of the epidermis and begin to develop at the end of the second month on the eyebrows, upper lip, and chin. The hair of the general body integument appears at the beginning of the fourth month. The first evidence of a hair anlage is the elongation of a cluster of epidermal cells in the inner germinal layer (Fig. 300 A). The bases of these cells project into the corium, and, above them, cells of the epidermis are arranged parallel to the 296 HISTOGENESIS surface. The elongated cells continue to grow downward until a cylindrical hair anlage is produced (Fig. 300 B, C). This consists of an outer wall formed of a single layer of columnar cells, continuous with the basal layer of the epidermis. This wall bounds a central mass of irregularly polygonal epidermal cells. About the hair anlage the mesenchyma forms a sheath, and at its base a condensation of mesenchyme produces the anlage of the hair papilla, which projects into the enlarged base of the hair anlage. As development proceeds, the hair anlage grows deeper into the corium and its base enlarges to form the hair bulb (Fig. 300 C). The hair differentiates from the basal epidermal cells surrounding the hair papilla. These cells give rise to a central core which grows toward the surface, Epitrichium “Central cells Epidermal anlage of. hair A Epidermal anlage of hair B EEE ONGC BIIBO LLY Epidermal anlage of hair C Mesenchymal sheath Hair bulb Yer et Hair papilla Fic. 300.—Section through the integument of the face of a 65 mm. human fetus showing three stages in the early development of the hair. X 330. distinct from the peripheral cells which form the outer sheath of the hair (Fig. 301). The central core of cells becomes the inner hair sheath and the shaft of the hair. At the sides of the outer hair sheath two swellings appear on the lower side of the obliquely directed hair anlage. The more superficial of these is the anlage of the sebaceous gland (Fig. 301). The deeper swelling is the “epithelial bed,” a region where the cells by rapid division contribute to the growth of the hair follicle. Superficial to the bulb, the cells of the hair shaft become cornified and differentiated into an outer cuticle, middle cortex, and central medulla. The hair grows at the base and is pushed out through the central cavity of the anlage, the cells of which degenerate. When the hair projects above the surface of the epidermis it breaks and carries with it the epitrichial layer. The mesenchymal MAMMARY GLANDS 207 tissue which surrounds the hair follicle in the neighborhood of the epithelial bed gives rise to the smooth fibers of the arrector pili muscle. Pigment granules de- velop in the basal cells of the hair and give it its characteristic color. — Sebaceous gland Epithelial bed Root of hair Frc. 301.—Longitudinal section through a developing hair from a five and one-half months’ human fetus (after Stéhr). -xX 220 ; The first generation of hairs are short-lived, all except those covering the face being cast off soon after birth. The coarser replacing hairs develop, at least in part, from new follicles. Thereafter hair is shed periodically throughout life. SWEAT GLANDS The sweat or sudoriparous glands begin to develop in the fourth month from the epidermis of the finger tips, the palms of the hands, and the soles of the feet. They are formed as solid downgrowths from the epidermis, but differ from hair anlages in having no mesenchymal papilla at their bases. During the sixth month the tubular anlages of the gland begin to coil and in the seventh month their lumina appear. The inner layer of cells forms the gland cells, while the outer cells become transformed into smooth muscle fibers which here arise from the ectoderm. In the axillary region sweat glands occur which are large and branched. MAMMARY GLANDS The tubular mammary glands peculiar to mammais are regarded as modified sweat glands. In embryos of 9 mm. (Figs. 94 and 118) an ectodermal thickening 298 HISTOGENESIS extends ventrolaterally between the bases of the limb buds on either side. This linear epidermal thickening is the milk line. In the future pectoral region of this line, by the thickening and downgrowth of the epidermis there is formed the papilla-like anlage of the mammary gland (Fig. 302 A). From this epithelial anlage buds appear (B) which elongate and form solid cords 15 to 20 in number, the anlages of the milk ducts (C). These branch in the mesenchymal tissue of the corium and eventually produce the alveolar end pieces of the mammary glands. In the region where the milk ducts open on the surface the epidermis is evagi- Gland anlage Epidermis - ! * Nipple Ea A 4 Epidermis Gland anlage : ON" of areola 4 Z \ Panniculus ~ adiposus aw). _ Pectoral muscle Fic. 302.—Sections representing three successive stages of development of the human mammary gland (Tourneux). A, fetus of 32 mm.; B, of 102 mm.; C, of 244 mm. *, Groove limiting glandular area. nated to form the nipple. The glands enlarge rapidly at puberty and are further augmented during pregnancy, while after parturition they become functionally active. The mammary glands are homologised with sweat glands because their development is similar, and because in the lower mammals their structure is the same. Rudimentary mam- mary glands (of Montgomery), which also resemble sweat glands, occur in the areola about the nipple. In many mammals numerous pairs of mammary glands are developed along the milk line (pig, dog, etc.); in some a pair of glands is developed in the pectoral region (primates, elephants); in others glands are confined to the inguinal region (sheep, cow, horse). In man supernumerary mammary glands developed along the milk line are of not infrequent occur- rence. THE NAILS The anlages of the nails proper are derived from the epidermis and may be recognized in fetuses of 45 mm. (CR). A nail anlage forms on the dorsum of each digit and extends from the tip of the digit almost to the articulation of the terminal phalanx. At the base of the anlage, that is, proximally, the epidermis is folded inward to form the proximal nail fold (posterior nail fold of the adult) (Fig. 303 THE NAILS 299 C). The nail fold also extends laterally on either side of the nail anlage and forms the lateral nail fold of the adult (A, B). The material of the nail is developed in the lower layer of the proximal nail fold (C). In certain of the epidermal cells, which according to Bowen represent a modified stratum lucidum, there are developed keratin or horn fibrils during the fifth month of fetal life. These appear without the previous formation of kerato- hyalin granules as is the case in the cornification of the stratum corneum. The cells flatten and form the plate-like structure of which the solid substance of the nail is composed. Thus the nail substance is formed in the proximal nail fold as Sole plate ~ Nail A -~ Lunula eo E hiv Eponychiwm vn = ape “Nail plate Sole plate... ae Nail fold fm Nail bed Fic. 303.—Figures showing the development of the nail. A, From a 40 mm. human fetus (X 20); B, from a 100 mm. fetus (X 13); C, longitudinal section through the nail anlage of a 100 mm. fetus (X 24). (Kollmann.) far distad as the outer edge of the Junula (the whitish crescent at the base of the adult nail). The underlying epidermis distal to the lunula takes no part in the development of the nail substance. The corium throws its surface of contact with the nail into parallel longitudinal folds which produce the longitudinal ridges of the nail. The nail is pushed toward the tip of the digit by the development of new nail substance in the region of the nail fold. The stratum corneum and the epitrichium of the epidermis for a time completely cover the nail matrix and are termed the eponychium (Fig. 303 C). Later, this is thrown off, but a portion of the stratum corneum persists during life as the curved fold of epidermis which adheres to the base of the adult nail. During life the nail constantly grows at its 300 HISTOGENESIS base (proximally), is shifted distally over the nail bed, and projects at the tip of the digit. The nails of man are the homologues of the claws and hoofs of other mammals. During the third month thickenings of the integument over the distal ends of the metacarpals and metatarsals become prominent. These correspond to the touch-pads on the feet of clawed mammals. Similar pads are developed on the under sides of the distal phalanges. THE HISTOGENESIS OF THE NERVOUS TISSUES The primitive anlage of the nervous system consists of the thickened layer of ectoderm along the mid-dorsal line of the embryo. This is the neural plate (Fig. 304 A, B) which is folded to form the newral groove (Figs. 77 A and 78). The edges Neural groove Neural plate Neural groove Neural plate 1 Ectoderm Neural groove Neural tube Neural cavity D Fic. 304.—Four sections showing the development of the neural tube in human embryos. 4, An early embryo (Keibel); B, at 2 mm. (Graf Spee); C, at 2 mm. (Mall); D, at 2.7 mm. (Kollmann). of the neural plate come together and form the neural tube (Fig. 304 C, D). The cranial portion of this tube enlarges and is constricted into the three primary vesicles of the brain (Fig. 324). Its caudal portion remains tubular and con- stitutes the spinal cord. From the cells of this tube, and the ganglion crest con- nected with it, are differentiated the nervous tissues, with the single exception of the nerve cells and fibers of the olfactory epithelium. The Differentiation of the Neural Tube.—The cells of the neural tube dif- ferentiate along two lines. There are formed: (1) nerve cells and fibers, in which irritability and conductivity have become the predominant functions; (2) meu- roglia cells and fibers which constitute the supporting or skeletal tissue peculiar to THE HISTOGENESIS OF THE NERVOUS TISSUES 301 the nervous system. The differentiation of these tissues has been studied by Hardesty in pig embryos (Amer. Jour. Anat., vol. 3, 1904). The wall of the neural tube, consisting at first of a single layer of columnar cells, becomes many- layered and finally three zones are differentiated (Fig. 305 A-D). As the wall becomes many-layered the cells lose their sharp outlines and form a compact, Marginal layer Manile layer Ependymal layer 4 he Marginal layer ‘Ependymal layer Internal limiting membrane M esoderm M arginal layer Ependymal layer } \Germinal -“ cell External limiting membrane Mantle layer Internal limiting membrane External limiting membrane Germinal cell , nternal limiting membrane ’ 4 Ay? vie D pe ee Ves ee oe si Mesoderm Marginal layer = Manile layer Ependymal layer Fic. 305.—Three stages in the early development of the neural tube showing the origin ot the syn- cytial framework (after Hardesty). > 690. A, From rabbit before the closure of neural tube; B, from 5 mm. pig after closure of tube; C, froma 7mm. pig embryo; D, from a 10 mm. pig embryo. * Boundary between nuclear layer and marginal layer. cellular syncytium which is bounded, on its outer and inner surfaces, by an exter- nal and internal limiting membrane (B). Ina10mm. embryo the cellular strands of the syncytium are arranged radially and nearly parallel (D). The nuclei are now so grouped that there may be distinguished three layers: (1) an inner epen- dymal zone with cells abutting on the internal limiting membrane, their processes 302 HISTOGENESIS extending peripherally; (2) a middle mantle or nuclear zone, and (3) an outer or marginal zone, non-cellular, into which nerve fibers grow. The ependymal zone contributes cells for the development of the mantle layer (D). The cellular mantle layer forms the gray substance of the central nervous system, while the fibrous marginal layer constitutes the white substance »f the spinal cord. The primitive germinal cells of the neural tube divide by mitosis and give rise to the ependymal cells of the ependymal zone and to indifferent cells of the mantle layer. From these latter arise spongioblasts and neuroblasts (Fig. 306). The spongioblasts are transformed into ewroglia cells and fibers, which form the supporting tissue of the central nervous system; the neuroblasts are primitive nerve cells, which, by developing cell processes, are converted into neurones. The neurones are the structural units of the nervous tissue. A Germinal cells Ependymal cells Indifferent cells Mitotic indifferent cells oO Pn eco SAP 242 805 Seg tS 09 0 Neuroblasts Neuroglia cells Fic. 306.—Diagrams showing the differentiation of the cells in the wall of the neural tube and the theo- retical derivation of the ependymal cells, neuroglia cells and neuroblasts (after Schaper). The Differentiation of the Neuroblasts into Neurones.—The nerve fibers are developed as outgrowths from the neuroblasts, and a nerve cell with all its pro- cesses constitutes a neurone or cellular unit of the nervous system. The origin of the nerve fibers as processes of the neuroblasts is best seen in the development of the root fibers of the spinal nerves. The Efferent or Ventral Root Fibers of the Spinal Nerves.—At the end of the first month clusters of neuroblasts separate themselves from the syncytium in the mantle layer of the neural tube. The neuroblasts become pear-shaped and from the small end of the cell a slender primary process grows out (Figs. 307 and 308). The process becomes the axis cylinder of a nerve fiber. The primary processes may course in the marginal layer of the neural tube, or, converging, may penetrate the marginal layer ventro-laterally and form the ventral roots of the THE UHISTOGENESIS OF THE NERVOUS TISSUES 303 Fic. 307.—A, Transverse section through the spinal cord of a chick embryo of the third day show- ing neuraxons (F) developing from neuroblasts of the neural tube and from the bipolar ganglion cells, d. B, Neuroblasts from the spinal cord of a seventy-two-hour chick. The three to the right show neuro- fibrils; C, incremental cone (Cajal). ‘Ventral root Fic. 308.—Transverse section of the spinal cord from human fetus of five weeks showing pear- shaped neuroblasts giving rise to ventral root fibers (His in Marshall). X 150. NC, Central canal of spinal cord. 304 HISTOGENESIS spinal nerves. Similarly, the efferent fibers of the cerebral nerves grow out from neuroblasts of the brain wall. Within the cytoplasm of the nerve cells and their primary processes strands of fine fibrils are early differentiated. These, the neurofibrille, are the conducting elements of the neurones. The cell bodies of the efferent neurones soon become multipolar by the development of branched secondary processes, the dendrites. The Development of the Spinal Ganglia.—A{ter the formation of the neural plate and groove a longitudinal ridge of cells appears on each side where the ecto- derm and neural plate are continuous (Fig. 309 A). This ridge of ectodermal Neural crest a O7 oS) ~ Neural crest a: Sad Ono ae SS 8 & Mesodermal segment Fic. 309.—Three stages in the development of the ganglion crest in human embryos (after von Len- hossek in Cajal). cells is the neural or ganglion crest. When the neural tube is formed and the ectoderm separates from it, the cells of the ganglion crest overlie the neural tube dorso-laterally (Fig. 309 C). As development continues they separate into right and left linear crests, distinct from the neural tube, and migrate ventro-laterally to a position between the neural tube and myotomes. In this position the ganglion crest forms a band of cells extending the whole length of the spinal cord and as far cranially as the otic vesicles. At regular intervals in its course along the spinal cord the proliferating cells of the crest give rise to enlargements, the spinal ganglia (Fig. 358). The spinal ganglia are arranged segmentally and are THE HISTOGENESIS OF THE NERVOUS TISSUES 305 connected at first by bridges of cells which later disappear. In the hind-brain region certain ganglia of the cerebral nerves develop from the crest but are not seg- mentally arranged. The Differentiation of the Afferent Neurones.—The cells of the spinal ganglia differentiate into (1) ganglion cells, and (2) supporting cells, groups which are comparable to the neuroblasts and spongioblasts of the neural tube. The neuro- blasts of the ganglia become fusiform and develop a primary process at either pole; thus these neurones are of the bipolar type (Fig. 307 d). The centrally directed processes of the ganglion cells converge and by elongation form the dorsal roots. They penetrate the dorso-lateral wall of the neural tube, bifurcate, and course cranially and caudally in the marginal layer of the spinal cord. By means of branched processes they come in con- tact with the neurones of the mantle layer. The peripheral processes of the ganglion cells, as the dorsal spinal roots, join the ventral roots, and, together with them, constitute the trunks of the spinal nerves (Fig. 325). The Differentiation of the Unipolar Ganglion Cells.—At first bipolar, the h ee majority of the ganglion cells become yy, Me Uy Ur unipolar either by the fusion of the two primary processes or by the bifurcation My Fic. 310.—A portion of a spinal ganglion from a of a single process (Fig. 310). The pro- ye Ge tsar Cale mated (Ga. cess of the unipolar ganglion is now T-shaped. Many of the bipolar ganglion cells persist in the adult, while others develop several secondary processes and thus become multipolar in form. In addition to forming the spinal ganglion cells, neuroblasts of the ganglion crest are believed to migrate ventrally and form the sympathetic ganglia (Fig. 325). The Neurone Theory.—The above account of the development of the nerve fibers is the one generally accepted at the present time. It assumes that the axis cylinders of all nerve fibers are formed as outgrowths, each from a single cell, an hypothesis first promulgated by His. The embryological evidence is supported by experiment. It has long been known from the work of Waller that if nerves are severed, the fibers distal to the point of section, and thus isolated from their nerve cells, will degenerate; also, that regeneration will take place from the central stumps of cut nerves, the fibers of which are still connected with their 20 306 HISTOGENESIS cells. More recently Harrison (Amer. Jour. Anat., vol. 5, 1906), experimenting on amphibian larve, has shown: (1) that no peripheral nerves develop if the neural tube and crest are re- moved; (2) that isolated ganglion cells growing in clotted lymph will give rise to long axis cylinder processes in the course of four or five hours. A second theory, supported by Schwann, Balfour, Dohrn, and Bethe, assumes that the nerve fibers are in part differentiated from a chain of cells, so that the neurone would represent a multicellular, not a unicellular structure. Apathy and O. Schulze modified this cell-chain theory by assuming that the nerve fibers differentiate in a syncytium which intervenes between the neural tube and the peripheral end organs. Held further modified this theory by assum- ing that the proximal portions of the nerve fibers are derived from the neuroblasts and ganglion cells and that these grow into a syncytium which by differentiation gives rise to the peripheral portion of the fiber. The Differentiation of the Supporting Cells of the Ganglia and Neural Tube. —The supporting cells of the spinal ganglia at first form a syncytium in the meshes of which are found the neuroblasts. They differentiate (1) into flattened capsule cells which form capsules about the ganglion cells, and (2) into sheath cells which ensheath the axis cylinder processes and are continuous with the capsules of the ganglion. It is probable that many of the sheath cells migrate peripherally along with the developing nerve fibers (Harrison). They are at first spindle- shaped, and, as primary. sheaths, enclose bundles of nerve fibers. Later, by the proliferation of the sheath cells, the bundles are separated into single fibers, each with its sheath (of Schwann), or newrilemma. Each sheath cell forms a segment of the neurilemma, the limits of contiguous sheath cells being indicated by con- strictions, the nodes of Ranvier. The Myelin or Medullary Sheath.—During the fourth month an inner mvelin sheath appears about many nerve fibers. This consists of a spongy framework of neurokeratin in the interstices of which a fatty substance, mvelin, is deposited. The origin of the myelin sheath is in doubt. By some (Ranvier) it is believed to be a differentiation of the neurilemma, the myelin being deposited in the substance of the nucleated sheath cell. By others (Kolliker, Bardeen) the myelin is regarded as a direct or indirect product of the axis cylinder. Its integrity is dependent at least upon the nerve cell and axis cylinder, for, when a nerve is cut, the myelin very soon shows degenerative changes. Furthermore, it may form where the sheath is absent. In the central nervous system there is no distinct neurilemma sheath invest- ing the fibers. Sheath cells are said to be present and most numerous during the period when myelin is developed. Hardesty derives the sheath cells in the central nervous system of the pig from a portion of the supporting cells, or spongioblasts, of the neural tube, and finds that these cells give rise to the myelin of the fibers. THE HISTOGENESIS OF THE NERVOUS TISSUES 307 Those fibers which are first functional receive their myelin sheaths first. The myelination of nerve fibers is only completed between the second and third year (Westphal). Many of the peripheral fibers, especially those of the sympa- thetic system, remain unmyelinated and supplied only with a neurilemma sheath. The myelinated fibers, those with a myelin sheath, have a glistening white ap- pearance and give the characteristic color to the white substance of the central nervous system and to the peripheral nerves. Ranson (Amer. Jour. Anat., vol. 12, 1911) has shown that large numbers of unmyelinated fibers occur in the peri- pheral nerves and spinal cord of adult mammals and man. Those found in the spinal nerves arise from the small cells of the spinal ganglia. B ot Fic. 311 —Ependymal cells from the neural tube of chick embryos. A, of first day; B, of third day. Golgi method (Cajal). The Development of the Supporting Cells—The spongioblasts of the neural tube (p. 302) differentiate into the supporting tissue of the central nervous system. ‘This includes the ependymal cells, which line the neural cavity, forming one of the primary layers of the neural tube, and neuroglia cells and their fibers. We have described how the strands of the syncytium formed by the spongio- blasts become arranged radially in the neural tube of early embryos (Fig. 305 D). As the wall of the neural tube thickens, the strands elongate pari passu and form a radiating branched framework (Fig. 302). The group of spongioblasts which line the neural cavity constitutes the ependymal layer. Processes from these 308 HISTOGENESIS cells radiate and extend through the whole thickness of the neural tube to its periphery. The cell bodies are columnar and persist as the lining of the central canal and ventricles of the spinal cord and brain (Fig. 312). Near the median line of the spinal cord, both dorsally and ventrally, the supporting tissue retains its primitive ependymal structure in the adult. Else- where the supporting framework is differentiated into mewroglia cells and fibers. The neuroglia cells form part of the spongioblastic syncytium and are scattered through the mantle and marginal layers of the neural tube. By proliferation wl ae Fic. 312.—Ependymal cells of the lumbar cord from a human fetus of 44 mm. (Golgi method, Cajal). A, Floor plate; B, central canal; C, line of future fusion of walls of neural cavity; E, ependy- mal cells; *, neuroglia cells and fibers. they increase in number and their form depends upon the pressure of the nerve cells and fibers which develop around them. Neuroglia fibers are differentiated (in a manner comparable to the formation of connective tissue fibers, Fig. 291) from the cytoplasm and cytoplasmic proc- esses of the neuroglia cells, and, as the latter primarily form a syncytium, the neuroglia fibers may extend from cell to cell. The neuroglia fibers develop late in fetal life and undergo a chemical transformation into meurokeratin, the same myelinated substance which is found in the sheaths of medullated fibers. CHAPTER XI THE MORPHOGENESIS OF THE SKELETON AND MUSCLES I. THE SKELETAL SYSTEM THE skeleton comprises (1) the axial skeleton (skull, vertebre, ribs, and ster- num), and (2) the appendicular skeleton (pectoral and pelvic girdles and the limb bones). Except for the flat bones of the face and skull, which develop directly in membrane, the bones of the skeleton exhibit first a blastemal or membranous stage, next a cartilaginous stage, and finalty a permanent osseous stage. For a detailed account of the development of the various bones of the skele- ton the student is referred to Bardeen, Keibel and Mall, vol. 1. AXIAL SKELETON The primitive axial skeleton of all vertebrates is the notochord or chorda dor- salis, the origin of which has been traced on pp. 33 and 35. The notochord con- stitutes the only skeleton of Amphioxus, whereas in fishes and amphibians it is replaced in part, and in higher animals almost entirely, by the permanent axial M yotome--$- aM otochord 4 Sclevol i> Anlage of vertebra => Sclerotome _Intersegmental Ectoderm..§ § 4 ...Intervertebral fissure artery ; --. Notochord 4 — I ntersegmental artery A Z FAR A B Fic. 313.—Frontal sections through the mesodermal segments of the left side of human embryos. A, at about 4 mm. showing the differentiation of the sclerotomes into less dense and denser regions; B, at about 5 mm. illustrating the union of the halves of successive sclerotomes to form the anlages of the vertebre. skeleton. In the development of mammals, this transient elastic rod disappears early except in the intervertebral discs where it persists as the nuclei pulposi. Vertebra and Ribs.—The mesenchyme derived from the sclerotomes grows mesad (Figs. 290 and 323) and comes to lie in paired segmental masses on either side of the notochord, separated from similar masses before and behind by the intersegmental arteries. In embryos of about 4 mm. each sclerotome soon differ- entiates into a caudal compact portion and a cranial less dense half (Fig. 313 A). 309 310 THE MORPHOGENESIS OF THE SKELETON AND MUSCLES From the caudal portions, horizontal tissue masses now grow toward the median line and enclose the notochord, thus establishing the body of each vertebra. Similarly, dorsal extensions form the vertebral arch, and ventro-lateral outgrowths, the costal processes. The looser tissue of the cranial halves also grows mesad and fills in the intervals between successive denser regions. The denser caudal half of each sclerotomic mass presently unites with the less dense cranial half of the sclerotome next caudad to form the anlages of the definitive vertebre (Fig. 313 B). Tissue bordering the cranial and caudal portion of the original sclerotome gives rise to the intervertebral discs. Since a vertebra is formed from parts of two adjacent sclerotomes, it is evident that the interseg- mental artery must now pass over the body of a vertebra and the myotomes and vertebre alternate in position. Following this blastemal stage centers of chondrification appear, two centers in the vertebral body, one in each half of the vertebral arch, and one in each costal process. These centers enlarge and fuse to form a cartilaginous vertebra; the union of the costal processes, which will give rise to ribs, with the body is, how- ever, temporary, an articulation forming later. Transverse and articular processes grow out from the vertebral arch, and the rib cartilages, having in the meantime formed tubercles, articulate with the transverse processes somewhat later. The various ligaments of the vertebral column arise from mesenchyme surrounding the vertebre. Finally, at the end of the eighth week, the stage of ossification sets in. A single center appears in the body, one in each half of the arch, and one near the angle of each rib (Fig. 296 A). The replacement of cartilage to form a solid mass is not completed until several years after birth. At about the seventeenth year secondary centers appear in the cartilage still covering the cranial and caudal ends of the vertebral body and form the disc-like, bony epiphysis. These unite with the vertebra proper to constitute a single mass at about the twentieth year. While the foregoing account holds for vertebre in general, a few deviations occur. When the ailas is formed a body differentiates as well, but it is appropri- ated by the body of the epistropheus (axis), thereby forming the tooth-like dens of the latter. The sacral and coccygeal vertebra represent reduced types. At about the twenty-fifth year the sacral vertebre unite to form a single bony mass, and a similar fusion occurs between the rudimentary coccygeal vertebrz. The ribs, originating as ventro-lateral outgrowths from the vertebral bodies, reach their highest development in the thoracic region. In the cervical region they are short; their tips fuse with the transverse processes and their heads with AXIAL SKELETON 311 the vertebral bodies, thus leaving intervals—the transverse foramina—through which the vertebral vessels course. In the lumbar region the ribs are again dimin- utive and are fused to the transverse processes. The rudimentary ribs of the sacral vertebra are represented by flat plates which unite on each side to form a pars lateralis of the sacrum. With the exception of the first coccygeal vertebra, ribs are absent in the most caudal vertebre. Sternum.—The sternal anlages arise as paired mesenchymal bands, with which the first eight or nine thoracic ribs fuse secondarily (Whitehead and Wad- dell, Amer. Jour. Anat., vol. 12, 1911). After the heart descends into the thorax, these cartilaginous sternal bars, as they may now be termed, unite in a cranio-cau- dal direction to form the sternum, at the same time incorporating a smaller mesial sternal anlage (Fig. 314). Ultimately one or two pairs of the most caudal ribs . Episternal Clavicle cartilage Fic. 314.—Formation of the sternum in a Fic. 315.—Sternum of a child, showing centers of human fetus during the third month (modified ossification. after Ruge). lose their sternal connections, the corresponding portion of the sternum consti- tuting the xiphoid process in part. At the cranial end of the sternum there are two imperfectly separated episternal cartilages with which the clavicles articulate. These usually unite with the longitudinal bars and contribute to the formation of the manubrium. Variations in the ossification centers are not uncommon, al- though a primitive, bilateral, segmental arrangement is evident (Fig. 315). In the two cranial segments, however, unpaired centers occur. The Skull.—The earliest anlage of the skull consists in a mass of dense mesen- chyme which envelops the cranial end of the notochord and extends cephalad into the nasal region. Laterally it forms wings which enclose the neural tube. Except in the occipital region, where there are indications of the incorporation into the skull of three or four vertebree, the skull is from the first devoid of segmentation. 312 THE MORPHOGENESIS OF THE SKELETON AND MUSCLES Chondrification begins in the future occipital and sphenoidal regions, in the median line, and extends cephalad and to a slight extent dorsad. At the same time, the internal ear becomes invested with a cartilaginous periotic capsule which eventually unites with the occipital and sphenoidal cartilages (Fig. 316). The chondrocranium, as it is termed, is thus confined chiefly to the base of the skull, the bones of the sides, roof, and the face being of membranous origin. Chondrification also occurs more or less extensively in the branchial arches, and, as will appear presently, the first two pairs contribute substantially to the forma- tion of the skull. In the period of ossification, which now ensues, it becomes evident that some bones which are separate in adult lower animals fuse to form compound bones in - Inter parietal Supra-occi pital ~-- Exocci pital --Cond yle { \ of ~Basi-occi pital Fic. 316.—Reconstruction of the chondro- Fic. 317.—Occipital bone of a human fetus cranium of a human embryo of 14 mm. (Levi in of four months (after Sappey). The portions still McMurrich). as, Alisphenoid; 60, basi-occipital; cartilaginous are shown as a background. _bs, basisphenoid; eo, exoccipital; m, Meckel’s car- tilage; os, orbitosphenoid; ~, periotic; ps, pre- sphenoid; so, sella turcica; s, supra-occipital. the human skull. The sphenoid and temporal bone} for example, represent five primitive pairs each. As such components may arise either in membrane or cartilage the mixed origin of certain adult bones is explained. Ossification of the Chondrocranium.—Occipital Bone.—Ossification begins i in the occipital region during the third month. Four centers appear at right angles about the foramen magnum (Fig. 317). From the ventral center arises the basilar (basi-occipital) part of the future bone; from the lateral centers the lateral (exoc- cipital) parts which bear the condyles, and from the dorsal, originally paired center the squamous (supra-occipital) part below the superior nuchal line. The squamous (interparietal) part above that line is an addition of intramembranous origin. These several components do not fuse completely until about the seventh year. AXIAL SKELETON 313 Sphenoid Bone.—Ten principal centers arise in the cartilage that corre- sponds to this bone (Fig. 318): (1 and 2) in each ala magna (alisphenoid) ; (3 and 4) in each ala parva (orbitosphenoid); (5 and 6) in the corpus between the ale magne (basisphenoid); (7 and 8) in each lingula; (9 and 10) in the corpus between the ale parvee (presphenoid). Intramembranous bone also enters into its compo- “t= Nasal septum 3\.... Perpendicular plate caeeCrista gallt Ala magna Ala parva (Alisphenoid) Presphenoid (Orbitosphenoid) My Le yy wi Lingula “Bi KC -- Pterygoid Basis phenoid process Fic. 318.—Sphenoid bone of a human fetus Frc. 319.—Ethmoid bone of a human fetus of of nearly four months (after Sappey). Parts still four months (modified after Kollmann). cartilaginous are represented in stipple. ? Cribriform plate A--~ Labyrinth sition, forming the orbital and temporal portion of each ala magna and the mesial lamine (Fawcett) of each pterygoid process (except the hamulus). Fusion of the various parts is completed during the first year. Ethmoid Bone.--The ethmoid cartilage consists of a mesial mass, which extends from the sphenoid to the tip of the nasal process, and of paired masses lateral to the olfactory fossa. The lower part Squamosum of the mesial mass persists as the cartilaginous nasal septum, but ossification of the upper por- tion produces the lamina perpendicularis and the crista galli (Fig. 319). The lateral masses ossify at first into the spongy bone of the eth- e ; moidal labyrinths. From this the definitive 7”?7"""" (A.g} honeycomb structure (ethmoidal cells) and the Big: 900. Gila et deapoeal Bone conche are formed through evaginations of the at birth. The portion of intracarti- laginous origin is represented in nasal mucous membrane and the coincident re- sGcéle sorption of bone. (Similar invasions of the mu- cous membrane and dissolution of bone produce the frontal, sphenoidal, and maxillary sinuses.) Fibers of the olfactory nerve at first course between the unjoined mesial and lateral masses. Later cartilaginous, and finally bony trabeculae surround these bundles of nerve fibers, and, as the cribriform plates, interconnect the three masses. Temporal Bone.—Several centers of ossification in the periotic capsule unite 314 THE MORPHOGENESIS OF THE SKELETON AND MUSCLES to form a single center from which the whole cartilage is transformed into the petrous and mastoid portions of the temporal bone (Fig. 320). The mastoid process is formed after birth by a bulging of the petrous bone, and its internal cavi- ties, the mastoid cells, are formed and lined by the evaginated epithelial lining of the middle ear. The squamosal and tympanic portions of the temporal bone are of intramembranous origin, while the styloid process originates from the proximal end of the second, or hyoid, branchial arch. Membrane Bones of the Skull.—From the preceding account it is evident that although the bones forming the base of the skull arise chiefly in cartilage, they receive substantial contributions from membrane bones. The remainder of the sides and roof of the skull is wholly of intramembranous origin, each of the parietals Incus Styloid process Tympanic ring Stylo-hyoid lig. Cricoid cartilage By Hyoid cartilage (greater horn) ‘Thyreoid cartilage Fic. 321.—Lateral dissection of the head of a human fetus, showing the derivatives of the branchial arches (after Kollmann). forming from a single center, the frontal from paired centers. At the incomplete angles between the parietals and their adjacent bones union is delayed for some time after birth, These membrane-covered spaces constitute the fontanelles. The vomer forms from two centers in the connective tissue flanking the lower border of the lamina perpendicularis of the ethmoid. The cartilage of the eth- moid thus invested undergoes resorption. Single centers of ossification in the mesenchyme of the facial region give rise to the nasal, lacrimal, and zygomatic, all pure membrane bones. Branchial Arch Skeleton.—The first branchial arch forks into an upper mawil- lary and a lower mandibular process (Fig. 119). Cartilage fails to appear in the maxillary processes, due to accelerated development, hence the palate bones and APPENDICULAR SKELETON 315 the mawille arise directly in membrane. Each palate bone develops from a single center of ossification. According to one view five centers contribute to the for- mation of each maxilla; Mall, however, maintains that there are but two centers, one giving rise to the portion bearing the incisor teeth, the other to the remainder of the maxilla. The entire core of the mandibular process becomes a cartilaginous bar, Meckel’s cartilage, which extends proximally into the tympanic cavity of the ear (Fig. 321). Membrane bone developing distally in the future body encloses Meckel’s cartilage and the inferior alveolar nerve, whereas proximally in the ramus the membrane bone merely lies lateral to these structures—hence the posi- tion of the adult mandibular foramen. The portion of Meckel’s cartilage enclosed in bone disappears, while the cartilage proximal to the mandibular foramen be- comes in order, the spheno-mandibular ligament, the malleus, and the incus (p. 389 and Fig. 387). Each second branchial arch comes into relation proximally with the periotic capsule. This upper segment of the cartilage becomes the stapes and the styloid process of the temporal bone (Figs. 321 and 387). The succeeding distal portion is transformed into the stylo-hyoid ligament and connects the styloid process with the distal end of the arch, which also undergoes intracartilaginous ossification to form the lesser horn of the hyoid bone. The cartilage of the third branchial arches ossifies and gives origin to the greater horns of the hyoid bone, while a plate connecting the two arches becomes its body. The fourth and fifth branchial arches co-operate in the formation of the thyreoid cartilage of the larynx. APPENDICULAR SKELETON Whereas the axial skeleton originates chiefly from the sclerotomes of the mesodermal segments, the appendicular skeleton is apparently derived from the unsegmented somatic mesenchyme. In embryos of 9 mm. mesenchymal conden- sations have formed definite blastemal cores in the primitive limb buds (Fig. 323). Following this blastemal stage the various bones next pass through a cartilagi- nous stage and finally an osseous one. Upper Extremity.—The clavicle is the first bone of the skeleton to ossify, centers appearing at each end. Prior to ossification it is compased of a peculiar tissue which makes it difficult to decide whether the bone is intramembranous or intracartilaginous in origin. 316 THE MORPHOGENESIS OF THE SKELETON AND MUSCLES The scapula arises as a single plate in which there are two chief centers of ossification. One center early forms the body and spine. The other, after birth, gives rise to the rudimentary coracoid process, which in lower vertebrates extends from the scapula to the sternum. Union between the coracoid process and the body does not occur until about the fifteenth year. The humerus, radius, and ulna ossify from single primary centers and two or more epiphyseal centers (Fig. 296 C-F). In the cartilaginous carpus there is a proximal row of three, and a distal row of four elements. Other inconstant cartilage may appear and subsequently dis- appear or become incorporated in other carpal bones. The pisiform is regarded as a sesamoid bone which develops in the tendon of the flexor carpi ulnaris; in the same category is the patella which forms in the tendon of the quadriceps extensor cruris. Lower Extremity.—The cartilaginous plate of the os coxe is at first so placed that its long axis is perpendicular to the vertebral column (Fig. 322). Later it rotates to a position parallel with the vertebral column and shifts slightly caudad to come into relation with the first three sacral vertebra. A retention of the membranous condition in the lower half of each primitive cartilaginous plate accounts for the obturator membrane which closes the foramen of the same name. Three centers of ossification appear, forming the ilium, ischium, and pubis. The three bones do not fuse completely until about puberty. The general development of the femur, tibia, fibula, tarsus, metatarsus, and phalanges is quite similar to that of the corresponding bones of the upper extremity. Anomalies.—Variations in the number of vertebra (except cervical) are not infre- quent. The last cervical and first lumbar vertebre occasionally bear ribs, due to the con- tinued development of the primitive costal processes. Cleft sternum or cleft xiphoid process represents an incomplete fusion of the sternal bars. Additional fingers or toes (polydactyly) may occur; the cause is obscure. Hare lip and cleft palate have already been mentioned (pp. 146, 149). II. THE MuscULAR SYSTEM The skeletal muscles, with the exception of those attached to the branchial arches, originate from the myotomes of the mesodermal segments (pp. 51, 292 and Fig. 323). Although the primitive segmental arrangement of the myotomes is, for the most part, soon lost, their original innervation by the segmental spinal nerves is retained throughout life. For this reason the history of adult muscles formed by fusion, splitting, or other modifications may be traced with consider- able certainty. THE MUSCULAR SYSTEM 317 The development of the human musculature is fully described by W. H. Lewis in Keibel and Mall, vol. 1. Fundamental Processes.—The changes occurring in the myotomes during the formation of adult muscles are referable to the operation of the following fun- damental processes: (1) A change in direction of the muscle fibers from their original cranio-caudal orientation in the myotome. The fibers of but few muscles retain this initial orientation. (2) A migration of myotomes, wholly or in part, to more or less remote regions. Thus the /atissimus dorsi originates from cervical myotomes, but finally attaches to the lower thoracic and lumbar vertebre and to the crest of the ilium. Other examples are the serratus anterior and the trapezius. (3) A fusion of portions of successive myotomes. The rectus abdominis illus- trates this process. (4) A longitudinal splitting of myotomes into several portions. Examples are found in the sterno- and omo-hyoid and in the trapezius and sterno-mastoid. (5) A tangential splitting into two or more layers. The oblique and the trans- verse muscles of the abdomen are formed by this common process. (6) A degeneration of myotomes, wholly or in part. In this way fascias, liga- ments, and aponeuroses may be produced. Muscles of the Trunk.—Ventral extensions grow out from the cervical and thoracic myotomes and a fusion that is well advanced superficially occurs between all the myotomes in embryos of 10 mm. A dorsal, longitudinal column of fused myotomes, however, can still be distinguished from the sheet formed from the combined ventral prolongations (Fig. 322). From the superficial portions of the dorsal column there arise by longitudinal and tangential splitting the various long muscles of the back which are innervated by the dorsal rami of the spinal nerves. The deep portions of the myotomes do not fuse, but give rise to the several intervertebral muscles, which thus retain their primitive segmental arrangement. The muscles of the neck, other than those innervated by the dorsal rami and those arising from the branchial arches, differentiate from ventral extensions of the cervical myotomes. Reference has already been made to the probable con- tribution from cervical myotomes to the formation of the diaphragm (p. 188). In the same way the thoraco-abdominal muscles arise from the more pronounced ventral prolongations of the thoracic myotomes which grow into the body wall along with the ribs (Fig. 322). 318 THE MORPHOGENESIS OF THE SKELETON AND MUSCLES The ventral extensions of the lumbar myotomes (except the first) and of the first two sacral myotomes do not participate in the formation of the body wall. If they persist at all, it is possible that they contribute to the formation of the lower limb. The ventral portions of the third and fourth sacral myotomes give rise to the muscles of the perineal region. Fic. 322.—Reconstruction of a 9 mm. human embryo to show the partially fused myotomes and the premuscle masses of the limbs (Bardeen and Lewis). X 13. Distally, in the upper extremity, the radius, ulna and hand plate are disclosed; in the lower extremity the os coxe anlage and the border vein show. Muscles of the Limbs.—It has generally been believed that the muscles of the extremities are developed from buds of the myotomes which grow into the anlages of the limbs. In sharks this is clearly the case, and in man the segmental nerve supply is suggestive, but not proof, of a myotomic origin. According to THE MUSCULAR SYSTEM 319 Lewis, “there are no observations of distinct myotome buds extending into the limbs.” A diffuse migration of cells from the ventral portion of the myotomes has been recorded by various observers, recently by Ingalls. These cells soon lose their epithelial character and blend with the undifferentiated mesenchyma of the limb buds (Fig. 323). From this diffuse tissue, which at about 10 mm. forms premuscle masses, the limb muscles are differentiated, the proximal muscles being the first to appear (Fig. 322). Spinal ganglion Dermatome Ventral rovt Myotome Spinal nerve Arm bud Proliferating cells of myotome oF Mesonephric duct Mesonephric tubule and glomerulus Celom Somatic mesoderm Frs. 323.—Transverse section of a 10.3 mm. monkey embryo showing the myotome and the mesenchyma of the arm bud (Kollmann). A, aorta; *, sclerotome. Muscles of the Head.—Distinct mesodermal segments do not occur in the head region. It is possible, however, that a premuscle mass, from which the eye muscles of man are developed, is comparable to three myotomic segments having a similar fate in the shark (cf. p. 366). The remaining muscles of the head differ from all other skeletal muscles in that they arise from the splanchnic mesoderm of the branchial arches and are innervated by nerves of a different category than those which supply myotomic muscles. The mesoderm of the first branchial arch gives rise to the muscles of mastication and to all other muscles innervated by the trigeminal nerve. Simi- 320 THE MORPHOGENESIS OF THE SKELETON AND MUSCLES larly the muscles of expression, and other muscles supplied by the facial nerve, originate from the second, or hyoid arch. The third arch probably gives origin to the pharyngeal muscles, and the third and fourth arches to the intrinsic muscles of the larynx. The muscles of the tongue are supplied by the n. hypoglossus, and therefore it has been assumed that they are derived from myotomes of the occipital region. According to Lewis, “there is no evidence whatever for this statement, and we are inclined to believe from our studies that the tongue musculature is derived from the mesoderm of the floor of the mouth.” Anomalies.—Variations in the form, position, and attachments of the muscles are common. Most of these anomalies are referable to the variable action of the several develop- mental factors listed on p. 317. CHAPTER XII THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM In discussing the histogenesis of the nervous tissue the early development of the neural tube has been described as an infolding of the neural plate (Fig. 78) and a closure of the neural groove (Fig. 304). The groove begins to close along the mid-dorsal line, near the middle of the body, in embryos of 2 mm. and the Mesencephalon Rhombencephalon Myelencephalon Amnion (cut) Mesodermal segment I4 Neural tube (not closed) “Ho Body stalk Fic. 324.—Human embryo of 2.4 mm. showing a partially closed neural tube and the brain vesicles (after Kollmann). X 36. closure extends both cranially and caudally (Fig. 324). Until the end of the third week there still persists an opening at either end of the neural tube, somewhat dor- sad. These openings are the neuropores (Fig. 330). Before the closure of the neuropores, in embryos of 2 to 2.5 mm. the cranial end of the neural tube has en- 2z 321 322 THE MORPHOGENESIS OF THE CENTRAI NERVOUS SYSTEM larged and is constricted at two points to form the three primary brain vesicles. The caudal two-thirds of the neural tube, which remains smaller in diameter, con- stitutes the anlage of the spinal cord. THE SPINAL CORD The spinal portion of the neural tube is at first nearly straight, but is bent with the flexure of the embryo into a curve which is convex dorsally. Its wall gradually thickens during the first month and the diameter of its cavity is di- Neural cavity Dorsal root Ependymal layer Spinal ganglion Manile layer Dorsal ramus Ventral root ? Roe! Syoss Nerve trunk Sympathetic ganglion Fic. 325.—Transverse section through a 10 mm. human embryo at the level of the arm buds showing the spinal cord and a spinal nerve of the right side. X 44. minished from side to side. By the end of the first month three layers have been developed in its wall as described in Chapter X, p. 301 (Fig. 325). These layers are the inner ependymal layer, which forms a narrow zone about the neural cavity, the middle mantle layer, cellular, and the outer marginal laver, fibrous. The Ependymal Layer is differentiated into a dorsal roof plate and a ventral floor plate (Fig. 326). Laterally, its proliferating cells contribute neuroblasts and neuroglia cells to the mantle layer. The proliferation of cells ceases first in the THE SPINAL CORD 323 ventral portion of the layer, which is thus narrower than the dorsal portion in 10 to 20 mm. embryos (Figs. 325 and 326). Consequently, the ventral portion Roof plate Dorsal funiculus Dorsal column Dorsal root Neural cavity Mantle layer + Ventral column Marginal layer Ependymal layer Floor plate Ventral median fissure Fig. 326.—Transverse section of the spinal cord from a 20 mm. human embryo. X 44. of the mantle layer is differentiated first. The neural cavity is at first somewhat rhomboidal in transverse section, wider dorsally than ventrally. Its lateral angle Dorsal funiculus Dorsal column Dorsal median Dorsal root septum Lat. funiculus Dura mater Central canal Ventral column Spinal ganglion Ventral funiculus Ventral median fissure Fic. 327.—Transverse section of the spinal cord from a 34 mm. human embryo, showing also the spinal ganglion and dura mater on the left side. X 44. forms the sulcus limitans (Fig. 334) which marks the subdivision of the lateral walls of the neural tube into the dorsal alar plate (sensory) and ventral basal plate 324 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM (motor). When the ependymal layer ceases to contribute new cells to the mantle layer its walls are approximated dorsally. As a result, in 20 mm. embryos the neural cavity is wider ventrally (Fig. 326). In the next stage, 34 mm., these walls fuse and the dorsal portion of the neural cavity is obliterated (Fig. 327). Ina 65 mm. (C R) fetus the persisting cavity is becoming rounded (Fig. 328). It forms the central canal of the adult spinal cord. The cells lining the central canal are ependymal cells proper. ‘Those in the floor of the canal form the persistent floor plate. Their fibers extend ventrad, reaching the surface of the cord in the depres- sion of the ventral median fissure. When the right and left walls of the ependymal layer fuse, the ependymal cells of the roof plate no longer radiate, but form a median septum (Fig. 327). Dorsal median septum Fasciculus gracilis Fasciculus cuneatus Dorsal root Dorsal column Substantia gelatinosa Lat. funiculus Central canal Lat. column \ a Ken Ventral funiculus Ventral median fissure Fic. 328.—Transverse section of the spinal cord from a 65 mm. human fetus. X 44. Later, as the marginal layers of either gide thicken and are approximated, the median septum is extended dorsally. Thus the roof plate is converted into part of the dorsal median septum of the adult spinal cord (Fig. 328). The Mantle Layer, as we have seen, is contributed to by the proliferating cells of the ependymal layer. A ventro-lateral thickening first becomes promi- nent in embryos of 10 to 15 mm. (Fig. 325). This is the ventral (anterior) gray column, or horn, which in later stages is subdivided, forming also a lateral gray column (Fig. 328). It is a derivative of the basal plate. In embryos of 20 mm. a dorso-lateral thickening of the mantle layer is seen, the cells of which constitute the dorsal (posterior) gray column, or horn (Figs. 327 and 328); about these cells the collaterals of the dorsal root fibers end. The cells of the dorsal gray column THE SPINAL CORD 325 thus form terminal nuclei for the afferent spinal nerve fibers and they are deriv- atives of the alar plate of the cord. Dorsal and ventral to the central canal the mantle layer forms the dorsal and ventral gray commissures. In the ventral floor plate nerve fibers cross from both sides of the cord and form the ventral (anterior) white commissure. The Marginal Layer is composed primarily of a framework of neuroglia and ependymal cell processes. Into this framework grow the axis cylinder processes of nerve cells, so that the thickening of this layer is due to the increasing number of nerve fibers contributed to it by extrinsic ganglion cells and neuroblasts. When their myelin develops, these fibers form the white substance of the spinal cord. The fibers have three sources (Fig. 360): (1) they may arise from the spinal ganglion cells, entering as dorsal root fibers and coursing cranially and caudally in the marginal layer; (2) they may arise from neuroblasts in the mantle layer of the spinal cord (a) as fibers which connect adjacent nuclei of the cord (fasciculi proprii or ground bundles), (0) as fibers which extend cranially to the brain; (3) they may arise from neuroblasts of the brain (a) as descending tracts from the brain stem, (0) as long descending cerebrospinal tracts from the cortex of the cerebrum. Of these fiber tracts (1) and (2 a) appear during the first month; (2 6) and (3 a) during the third month; (3 5) at the end of the fifth month. The dorsal root fibers from the spinal ganglion cells, entering the cord dorso- laterally, subdivide the white substance of the marginal layer into a dorsal funic- ulus and lateral funiculus. The lateral funiculus is marked off by the ventral root fibers from the ventral funiculus (Fig. 327). The ventral root fibers, as we have seen, take their origin from the neuroblasts of the ventral gray column in the mantle layer. They are thus derivatives of the basal plate. The dorsal funiculus is formed chiefly by the dorsal root fibers of the ganglion cells and is subdivided into two distinct bundles, the fasciculus gracilis, median, and the fasciculus cuneatus, lateralin position. The dorsal funiculi are separated only by the dorsal median septum (Fig. 328). The lateral and ventral funiculi are composed of fasciculi propria or ground bundles, originating in the spinal cord, of ascending tracts from the cord to the brain, and of the descending fiber tracts from the brain. The fibers of these fasciculi intermingle and the fasciculi are thus without sharp boundaries. The floor plate of ependymal cells lags behind in its development, and, as it is inter- posed between the thickening right and left walls of the ventral funiculi, these do not meet and the ventral median fissure is produced (cf. Figs. 325 and 328). 326 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM The development of myelin in the nerve fibers of the cord begins late in the fourth month of fetal life and is completed between the fifteenth and twentieth years (Flechsig, Bechterew). Myelin appears first in the root fibers of the spinal nerves and in those of the ventral commissure, next in the ground bundles and dorsal funiculi. The cerebrospinal (pyramidal) fasciculi are the last in which myelin is developed; they are myelinated during the first and second years. As myelin appears in the various fiber tracts at different periods, this condition has been utilized in tracing the extent and origin of the various fasciculi in the central nervous system. The Cervical and Lumbar Enlargements.—At the levels of the two nerve plexuses, supplying the upper and lower extremities, the spinal cord enlarges. As the fibers to the muscles of the extremities arise from nerve cells in the ventral gray column, the num- ber of these cells and the mass of the gray substance is increased; since larger numbers of fibers from the Cerebrum .. Mesencephalon.. Cerebellum- Cervical < integument of the limbs also enter the cord at this enlargement f level, there are likewise present more cells about which sensory fibers terminate. There is formed con- sequently at the level of the origin of the nerves of Lumbar enlargement the brachial plexus the cervical enlargement, opposite the origins of the nerves of the lumbo-sacral plexus the lumbar enlargement (Fig. 329). At the caudal end of the neural tube in a 110 mm. f (C R) fetus an epithelial sac is formed which is ad- Fic. 320.—Dissection of herent to the integument. Cranial to the sac the the brain and cord of a three central canal is obliterated, this part of the neural months’ fetus, showing the cer- : ; vical and lumbar enlargements tube forming the filwm terminale. The caudal end (after Koélliker in Marshall). Manat aoe of the central canal is irregularly expanded and is known as the terminal ventricle. After the third month the vertebral column grows faster than the spinal cord. As the cord is fixed to the brain the vertebra and the associated roots and ganglia of the spinal nerves shift caudally along the cord. In the adult the origin of the coccygeal nerves is oppogite the first lumbar vertebra and the nerves course ob- liquely downward nearly parallel to the spinal cord. As the tip of the neural tube is attached to the coccyx, its caudal portion becomes stretched into the slender, solid cord known as the filum terminale. The obliquely coursing spinal nerves, with the filum terminale, constitute the cauda equina. THE BRAIN 327 THE BRAIN We have seen that in embryos of 2 to 2.5 mm. the neural tube is nearly straight, but that its cranial end is enlarged to form the anlage of the brain (Fig. 324). The appearance of two constrictions in the wall of the anlage subdivides it into the three primary brain vesicles—the fore-brain or prosencephalon, mid-brain or mesencephalon, and hind-brain or rhombencephalon. In embryos of 3.2 mm., estimated age four weeks, three important changes have taken place (Fig. 330): (1) the neural tube is bent sharply in the mid-brain region (the cephalic flexure) so that the axis of the fore-brain now forms a right : Cor pus striatum Anterior : Pallium neuropore Pallium of telencephalon Diencephalon — Anterior neuro pore ATesence phalon ~ My SY oN : “Cephalic flexure Mesencephalon Optic recess Isthmus Future pontine flexure Optic vesicle Rhombencephalon Rhombencephalon Wu Future pontine_|{ flexure ia | Kataarin® Fic. 330.—Reconstructions of the brain of a 3.2 mm. human embryo (after His). X about 35. A, Lateral surface; B, sectioned in the median sagittal plane. angle with the axis of the hind-brain; (2) the fore-brain shows indication dorsally of a fold, the margo thalamicus, which subdivides it into the telencephalon and the diencephalon; (3) the lateral walls of the fore-brain show distinct evaginations, the optic vesicles, which project laterad and caudad. A ventral bulging of the wall of the hind-brain indicates the position of the future pontine flexure. In embryos of 7 mm. (five weeks) the neuropores have closed (Fig. 331). The cephalic flexure, now more marked, forms an acute angle, and the pontine flexure, just indicated in the previous stage, is now a prominent ventral bend in the ventro-lateral walls of the hind-brain. This flexure forms the boundary line which subdivides the rhombencephalon into a cranial portion, the meten- 328 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM cephalon, and into a caudal portion, the myelencephalon. At a third bend the whole brain is flexed ventrally at an angle with the axis of the spinal cord. This bend is the cervical flexure and is the line of demarcation between the brain and spinal cord (cf. Fig. 333 A). The telencephalon and diencephalon are more dis- tinctly subdivided, and the evaginated optic vesicle forms the optic cup attached to the brain wall by a hollow stalk, in which later grows the optic nerve. The walls of the brain show a distinct differentiation in certain regions. This is especially marked in the myelencephalon, which has a thicker ventro-lateral wall and thinner dorsal wall. Embryos of 10.2 mm. show the structure of the brain at the beginning of the second month (Figs. 341 and 344). The five brain regions are now sharply dif- A B Diencephalon Mesencephalon Thalamus Pallium Mesencephalon Cephalic , flexure AMeten- cephalon Corpus striatum Optic recess Hy poolamus’’ Medulla oblongata Tharine Hil Fic. 331.—Reconstructions of the brain of a 7 mm. human embryo (His). A, Lateral view; B, in median sagittal section. ferentiated externally, but the boundary line between the telencephalon and dien- cephalon is still indistinct. The telencephalon consists of paired, lateral out- growths, the anlages of the cerebral hemispheres and rhinencephalon (olfactory brain). In Fig. 359 the external form of the brain is seen with the origins of the cerebral nerves. It will be noted that, with the exception of the first four (the olfactory, optic, oculomotor, and trochlear), the cerebral nerves take their super- ficial origin from the myelencephalon. The cephalic flexure forms a very acute angle, and, as a result, the long axis of the fore-brain is nearly parallel to that of the hind-brain (Fig. 359). The ocu- lomotor nerve takes its origin from the ventral wall of the mesencephalon. Dor- sally there is a constriction, the isthmus, between the mesencephalon and meten- THE BRAIN 329 cephalon, and here the fibers of the trochlear nerve take their superficial origin. The dorsal wall of the myelencephalon is an exceedingly thin ependymal layer which becomes the tela chorioidea. The ventro-lateral walls of this same region, on the other hand, are very thick. A median sagittal section of a brain at a somewhat later stage shows the cervical, pontine, and cephalic flexures well marked (Fig. 332). The thin dorso- lateral roof of the myelencephalon has been removed. The telencephalon is a paired structure. In the figure its right half projects cranial to the primitive median wall of the fore-brain which persists as the lamina terminalis (cf. Fig. 342). The floor of the telencephalon is greatly thickened caudally as the anlage of the o Cerebral aqueduct Cerebral peduncle, ., Mesencephalon _ ae Hypothalamus Epithalamus , +4 ss. Ahombence phalic isthmus ' Cerebellum - Metence phalon Ying é ine —~y, i234 | Corpus striatum Pons a Lamina terminalis yu ; : ve F SY Spinal cord Rhinence phal on Fic. 332.—Brain of a 13.6 mm. human embryo in median sagittal section (after His in Sobotta). 1, Optic recess; 2, ridge formed by optic chiasma, 3; 4, infundibular recess. corpus striatum. A slight evagination of the ventral wall of the telencephalon just cranial to the corpus striatum marks the anlage of the rhinencephalon. The remaining portion of the telencephalon forms the pallium or cortex of the cerebral hemispheres. The paired cavities of the telencephalon are the Jateral (first and second) ventricles, and these communicate through the interventricular foramina (Monroi) with the cavity of the diencephalon, the third ventricle. The cavities of the olfactory lobes communicate during fetal life with the lateral ventricles and were formerly called the first ventricles. The crossing of a portion of the optic nerve fibers in the floor of the brain forms the optic chiasma, and this, with the transverse ridge produced by it inter- nally, is taken as the ventral boundary line between the telencephalon and dien- 330 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM cephalon (Fig. 332). A dorsal depression separates the latter from the mesenceph- alon. The lateral wall of the diencephalon is thickened to form the thalamus, the caudal and lateral portion of which constitutes the metathalamus. From the metathalamus are derived the geniculate bodies. In the median dorsal wall, near the caudal boundary line of the diencephalon, an outpocketing begins to appear in embryos of five weeks (Fig. 332). This is the epithalamus, which later gives rise to the pineal body, or epiphysis. The thalamus is marked off from the more ventral portion of the diencephalic wall, termed the hypothalamus, by the obliquely directed sulcus hypothalamicus (Fig. 341). Cranial to the optic chiasma is the optic recess, regarded as belonging to the telencephalon (Fig. 332). Caudal to it is the pouch-like infundibulum, an extension from which during the fourth week forms the posterior lobe of the hypophysis. Caudal to the infundibulum the floor of the diencephalon forms the tuber cinereum and the mammillary recess; the walls of the latter thicken later and give rise to the mammillary bodies. An oblique transverse section through the telencephalon and hypothalamic portion of the diencephalon (Fig. 343) shows the relation of the optic recess to the optic stalk, the infundibulum, and Rathke’s pocket, and the extension of the third ventricle, the proper cavity of the dien- cephalon, into the telencephalon between the corpora striata. The mesencephalon in 13.6 mm. embryos (Fig. 332) is distinctly marked off from the metencephalon by the constriction which is termed the isthmus. Dorso- lateral thickenings form the corpora quadrigemina. Ventrally, the mesencephalic wall is thickened to form the tegmentum and crura cerebri. In the tegmentum are located the nuclei of origin for the oculomotor and trochlear nerves. The former, as we have seen, takes its superficial origin ventrally, while the trochlear nerve fibers bend dorsad, cross at the isthmus, and emerge on the opposite side. As the walls of the mesencephalon thicken, its cavity later is narrowed to a canal, the cerebral aqueduct (of Sylvius). The walls of the metencephalon are thickened dorsally and laterally to form the anlage of the cerebellum. Its thickened ventral wall becomes the pois (Varolii). Its cavity constitutes the cranial portion of the fourth ventricle. The caudal border of the pons is taken as the ventral boundary line between the metencephalon and myelencephalon. The myelencephalon forms the medulla oblongata. Its dorsal wall is a thin, non-nervous ependymal layer, which later becomes the posterior medullary velum. From its thickened ventro-lateral walls the last eight cerebral nerves take their origin. Its cavity forms the greater part of the fourth ventricle which opens caudally into the central canal of the THE BRAIN ’ 331 spinal cord, cranially into the cerebral aqueduct. The increase in the flexures of the brain and the relative growth of its different regions may be seen by comparing the brains of embryos of four, five, and seven weeks (Fig. 333). A Mesencephalon I sthmus Diencephaton Metencephalon Telencephalon. —Olic vesicle ~-M yelencephalon Cervical flexure A yelence phalon Metencephalon \- M yelencephalon Fic. 333.—Brains of human embryos, from reconstructions by His: A, 4.2 mm. embryo (X 20); B, 6.9 mm. embryo (X 16); C, 18.5 mm. embryo (X 4). vu, Optic vesicle; im, infundibulum; m, mam- millary body; f, pontine flexure; ol, olfactory lobe; 6, basilar artery; », Rathke’s pouch (American Text-Book of Obstetrics). In the table on page 332 are given the primitive subdivisions of the neural tube and the parts derived from them: 332 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM THE DERIVATIVES OF THE NEURAL TUBE Primary VESICLES. SUBDIVISIONS. DERIVATIVES. CAVITIES. Telencephalon Cerebral cortex Lateral ventricles Corpora striata Cranial portion of Rhinencephalon third ventricles Diencephalon Epithalamus Third ventricle (Pineal body) Thalamus Prosencephalon Optic tract Hypothalamus Hypophysis Tuber cinereum Mammillary bodies Mesencephalon Mesencephalon Corpora quadrigemina | Aqueductus cerebri Tegmentum . Crura cerebri Rhombencephalon Metencephalon Cerebellum Fourth ventricle Pons Myelencephalon Medulla oblongata Spinal cord Spinal cord Central canal. 7 THE LATER DIFFERENTIATION OF THE SUBDIVISIONS OF THE BRAIN Myelencephalon.—We have seen that the wall of the spinal cord differen- tiates dorsally and ventrally into roof plate and floor plate, laterally into the alar A B - Roof plate Rae, Mantle layer. ye Sulcus limitans Ependymal la yer Marginal Basal plate laycr Spinal ganglion x. Y Ventral spinal root Fic. 334.—Transverse sections. X 44. A, Through the upper cervical region of the spinal cord in a 10 mm. human embryo; B, through the caudal end of the myelencephalon. plate and basal plate. The boundary line between the alar and basal plates is the sulcus limitans (Fig. 334 A). The same subdivisions may be recognized in the myelencephalon. It differs from the spinal cord, however, in that the roof plate THE BRAIN 333 is broad, thin, and flattened to form the ependymal layer (Figs. 334 B and 335). In the alar and basal plates of the myelencephalon the marginal, mantle, and Alar plate Sulcus limitans Basal plate MN Ganglion W jugulare a N. hypoglossus NV. accessorius Fic. 335.—Transverse sections through the myelencephalon of a 10.2 mm. embryo (His). X 37. A, Through the nuclei of origin of the spinal accessory and hypoglossal nerves; B, through the vagus and hypoglossal nerves. ependymal zones are differentiated as in the spinal cord (Fig. 335). Owing to the formation of the pontine flexure at the beginning of the second month, the roof Inner layer Roof plate Tractus solitarius y. | Spinal tract of NV. trigeminus “6 Neuroblasts from alar plate Marginal layer N. hypoglossus Septum medulle Neuroblasts from alar plate (Rudiment of accessory olive) Fic. 336.—Transverse section through the myelencephalon of a 22 mm. embryo (His). X 10. plate is broadened} especially in the cranial portion of the myelencephalon, and the alar plates bulge laterally (Figs. 336 and 337 A). The cavity of the myelen- 334 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM cephalon is thus widened from side to side and flattened dorso-ventrally. This is most marked cranially where, between the alar plates of the myelencephalon and metencephalon, are formed the lateral recesses of the fourth ventricle (Figs. 337 and 353). Into the ependymal roof of the myelencephalon blood vessels grow, and, invading the lateral recesses, form there the chorioid plexus of the fourth ventricle. The plexus consists of small, finger-like folds of the ependymal layer and its covering mesenchymal layer. The line of attachment of the epen- dymal layer to the alar plate is known as the rhombic lip and later becomes the tenia and obex of the fourth ventricle (Fig. 337 B). Cc Mid-brain Lateral lobe of cerebellum Lobules of vermis \ Medulla Flocculus Rhombic lip oblongata B Lateral lobe of Pyramis cerebellum _ Cor pora quadiizemnnia. Cerebrum f Anlage of vermis f Lateral lobe of * cerebellum Rhombic lip Obex Flocculus Z : Nodulus Fic. 337.—Dorsal views of four stages in the development of the cerebellum. 4, of a 13.6 mm. em- bryo (His); B, of a 24 mm. embryo; C, of a 110 mm. fetus; D, of a 150 mm. fetus. In early stages the floor of the myelencephalon is constricted transversely by the so-called rhombic grooves, six in number; the intervals between successive grooves are neuromeres (cf. Figs. 96 and 122). Some have viewed these as evi- dential of a former segmentation of the head similar to that of the trunk. It is more probable, however, that they merely stand in relation to certain cerebral nerves and hence their segmental arrangement is secondary. The further growth of the myelencephalon is due: (1) to the rapid formation of neuroblasts, derived from the ependymal and mantle layers; (2) to the devel- opment of nerve fibers from these neuroblasts; (3) to the development and THE BRAIN 335 growth into it of fibers from neuroblasts in the spinal cord and in other parts of the brain. The neuroblasts of the basal plates early give rise chiefly to the efferent fibers of the cerebral nerves (Fig. 335). They thus constitute motor nuclei of origin of the trigeminal, abducens, facial, glossopharyngeal, vagus complex, and hypo- glossal nerves, nuclei corresponding to the ventral and lateral gray columns of the spinal cord. The basal plate likewise produces part of the reticular formation which is derived in part also from the neuroblasts of the alar plate (Fig. 336). The axons partly cross as external and internal arcuate fibers and form a portion of the median longitudinal bundle, a fasciculus corresponding to the ventral ground bundles of the spinal cord. Other axons grow into the marginal zone of the same side and form intersegmental fiber tracts. The reticular formation is thus differ- entiated into a gray portion, situated in the mantle zone, and into a white portion, located in the marginal zone (Fig. 336). The marginal zone is further added to by the ascending fiber tracts from the spinal cord and the descending pyramidal tracts from the brain. As in the cord, the marginal layers of each side remain distinct, being separated by the cells of the floor plate. The alar plates differentiate later than the basal plates. The afferent fibers of the cerebral nerves first enter the mantle layer of the alar plates, and, coursing upward and downward, form definite tracts (fractus solitarius, descending tract of fifth nerve). To these are added tracts from the spinal cord so that an inner gray and an outer white substance is formed. Soon, however, the cells of the mantle layer proliferate, migrate into the marginal zone, and surround the tracts. These neuroblasts of the alar plate form groups of cells along the terminal tracts of the afferent cerebral nerves (which correspond to the dorsal root fibers of the spinal nerves) and constitute the receptive or terminal nuclei of the fifth, seventh, eighth, ninth, and tenth cerebral nerves. Caudally, the nucleus gracilis and nucleus cuneatus are developed from the alar plates as the terminal nuclei for the afferent fibers which ascend from the dorsal funiculi of the spinal cord. The axons of the neuroblasts forming these receptive nuclei decussate through the reticulor formation chiefly as internal arcuate fibers and ascend to the thalamus as the median lemniscus. There are developed from neuroblasts of the alar plate other nuclei, the axons of which connect the brain stem, cerebellum, and fore-brain. Of these the most conspicuous is the inferior olivary nucleus. The characteristic form of the adult myelencephalon is determined by the further growth of the above-mentioned structures. The nuclei of origin of the 336 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM cerebral nerves, derived from the basal plate, produce swellings in the floor of the fourth ventricle which are bounded laterally by the sulcus limitans. The terminal nuclei of the mixed and sensory cerebral nerves lie lateral to this sulcus. The enlarged cuneate and gracile nuclei bound the ventricle caudally and laterally as the cuneus and clava. The inferior olivary nuclei produce lateral rounded prominences and ventral to these are the large cerebrospinal tracts or pyramids. The Metencephalon.—Cranial to the lateral recesses of the fourth ventricle the cells of the alar plate proliferate ventrally and form the numerous rela- tively large.nuclei of the pons. The axons from the cells of these nuclei mostly cross to the opposite side and form the brachium pontis of the cerebellum. Cere- bral fibers from the cerebral peduncles end about the cells of the pontine nuclei. Others pass through the pons as fascicles of the pyramidal tracts. B A Mesencephalon Mesencephalon Cerebellum t= Posterior medullary velum Aaa edblaks) velum Fic. 338.—Median sagittal section of the cerebellum and part of mid-brain. A, from a 24 mm. embryo; B, from a 150 mm. fetus. Cerebellum.—When the alar plates of the cranial end of the myelencephalon are bent out laterally the caudal portions of their continuations into the meten- cephalic region are carried laterally also. As a result, the alar plate of the meten- cephalon takes up a transverse position and forms the anlages of the cerebellum (Fig. 337 A). During the second month the paired cerebellar plates thicken and bulge into the ventricle (Fig. 338 A). Near the mid-line paired thickenings indi- cate the anlages of the vermis, while the remainder of the alar plates form the anlages of the lateral lobes or cerebellar hemispheres (Figs. 337 B and 353). The cerebellar anlages grow rapidly both laterally and in length, so that their surfaces are folded transversely. During the third month their walls bulge out- ward and form on either side a convex lateral lobe connected with the pons by the brachium pontis (Fig. 337 C). In the meantime the anlages of the vermis have THE BRAIN 337 fused in the mid-line, producing a single structure marked by transverse fissures. The rhombic lip gives rise to the flocculus and nodulus. Between the third and fifth months the cortex cerebelli grows more rapidly than the deeper layers of the cerebellum and its principal lobes, folds and fissures are formed (Fig. 337 C, D). The hemispheres derived from the lateral lobes are the last to be differentiated. Their fissures do not appear until the fifth month. Cranial to the cerebellum the wall of the neural tube remains thin dorsally and constitutes the anterior medullary velum of the adult (Fig. 338 B). Caudally, the ependymal roof of the fourth ventricle becomes the posterior medullary velum. The points of attachment of the vela remain approximately fixed, while the cere- bellar cortex grows enormously. As a result, the vela are folded in under the expanding cerebellum (Fig. 338). The anlages of the cerebellum show at first differentiation into the same three layers which are typical for the neural tube. During the second and third months, cells from the ependymal, and perhaps from the mantle layer of the rhombic lip migrate to the surface of the cerebellar cortex and give rise to the molecular and granular layers which are character- istic of the adult cerebellar cortex (Schafer). The later differentiation of the cortex is only completed at, or after, birth. The cells of the granular layer become unipolar by a process of unilateral growth. The Purkinje cells differentiate later. Their axons and those of enter- ing afferent fibers form the deep medullary layer of the cerebelium. The cells of the mantle layer may take little part in the development of the cerebellar cortex, but give rise to neuroglia cells and fibers and to the internal nuclei. Of these the dentate nucleus may be seen at the end of the third month; later, its cellular layer becomes folded, producing its characteristic convolutions. The fibers arising from its cells form the greater part of the brachium conjunctivum. (For a detailed account of the development of the cerebellum see Streeter, in Keibel and Mall, vol. 2). Mesencephalon.—-The basal and alar plates can be recognized in this sub- division of the brain and each differentiates into the three primitive layers (Fig. 339). In the basal plate the neuroblasts give rise to the axons of motor nerves— the oculomotor cranial in position, the trochlear caudal (Fig. 339 B). In ad- dition to these nuclei of origin, the nucleus ruber (red nucleus) is developed in the basal plates ventral and somewhat cranial to the nucleus of the oculomotor nerve. The origin of the cells forming the red nucleus is not definitely known. The alay plates form the paired superior and inferior colliculi which together constitute the corpora quadrigemina (Figs. 337 B and 349). The plates thicken and neuroblasts migrate to their surfaces, forming stratified ganglionic layers com- parable to the cortical layers of the cerebellum and the cerebellar nuclei. With the development of the superior and inferior colliculi the cavity of the mesen- cephalic region decreases in size and becomes the cerebral aqueduct. 22 338 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM The mantle layer of the basal plate region is enclosed ventrally and laterally by the fiber tracts which develop in the marginal zone. Ventro-laterally appear the median and lateral lemnisci and ventrally develop later the descending tracts from the cerebral cortex, which together constitute the peduncles of the cerebrum. DIV. -Marginal layer _..Nucleus N.III. ----Root fibers N. ITI. 1 AS a i Frc. 339.—Transverse sections through the mesencephalon of a 10.2 mm. embryo (His). A, Through the isthmus and origin of the trochlear nerve; B, through the nucleus of origin of the oculomotor nerve; D. IV, decussation of oculomotor nerve; M.l., mantle layer. The Diencephalon.—In the wall of the diencephalon we may recognize laterally the alar and basal plates, dorsally the roof plate, and ventrally the floor plate (Fig. 340). The roof plate expands, folds as seen in the figure, and into the folds extend blood capillaries. The roof plate thus forms the ependymal lining Roof plate (with chorioid plexus) . Alar plate or Thalamus ‘Sulcus limitans or S. hypothalamicus Basal plate or Hypothalamus Mammillary recess Fic. 340.—Transverse section through the diencephalon of a 13.8 mm embryo (His). X 29. of the éela chorioidea of the third ventricle. The vessels and ingrowing mesenchy- mal tissue form the chorioid plexus. Cranially, the tela chorioidea roofs over the median portion of the telencephalon and is folded laterally into the hemispheres as the chorioid plexus of the lateral ventricles. Laterally, the roof plate is attached to the alar plates and at their point of union are developed the ganglia habenule. THE BRAIN 339 The pineal body, or epiphysis, is developed caudally as an evagination of the roof plate. It appears at the fifth week (Fig. 335) and is well developed by the third month (Fig. 342). Into the thickened wall of the anlage is incorporated a certain amount of mesenchymal tissue and thus the pineal body proper is formed. The alar plate is greatly thickened and becomes the anlage of the thalamus and metathalamus. ‘The latter, really a part of the thalamus, gives rise to the lateral and median geniculate bodies. The saulcus hypothalamicus (Fig. 341) forms the boundary line between the thalamus (alar plate) and the hypothalamus (basal plate plus the floor plate). Hypothalamus Sulcus hypothalamicus Pallium Mammillary recess Cor pus striatum Tnfundibulum Optic ridge Fic. 341.—Median sagittal section of the fore- and mid-brain regions of a brain from a 10.2 mm. embryo (after His). » This sulcus thus corresponds to the salcus limitans of the spinal cord and brain stem. The basal plate is comparatively unimportant in the diencephalic region, as no nuclei of origin for motor nerves are developed here. In the floor plate the ridge formed by the optic chiasma constitutes the pars optica hypothalamica. The Hypophysis —The infundibulum develops as a recess caudal to the pars optica hypothalamica (Figs. 342 and 343). At its extremity is the sac-like anlage of the posterior lobe of the hypophysts or pituitary body. During the fourth week the infundibular anlage comes into contact with Rathke’s pouch, the epi- thelial anlage of the anterior lobe of the hypophysis (Fig. 343). The epithelial 340 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM anlage is at first flattened and soon is detached from its epithelial stalk. Later, it grows laterally and caudally about the anlage of the posterior lobe, and, during Thalamus i Pineal body (epithalamus) ; Cer ebral peduncle ' Cerebral aqueduct " Mesence phalon Dience phalon_, Chorioid plexus Cor pus striatum~ b, | Isthmus 38— Cerebellum '~ Metencephalon ~~ — Rhomboid fossa ~~ Myelencephalon Telencephalon A > Pons ~ ~~ é Optic Hypo- = + Johiasma physis Medulla ~ Lamina lena J Hypothalamus ones Rhinence phalon Lf. : /]~~- Spinal cord t : f ~~ Central canal Fic. 342.—Median sagittal section of the brain from a fetus of the third month (His in Sobotta). Foramen Monroi Third ventricle Optic vesicle Es Lens vesicle gD Infundibulum Z Rathke’s pocket—Gare Fic. 343.—Oblique transverse section through the diencephalon and telencephalon of a 10 mm. embryo. X 61. the second month, its wall is differentiated into convoluted tubules which obliter- ate its cavity. The tubules become closed glandular follicles surrounded by a rich network of blood vessels and produce an important internal secretion. Coinci- THE BRAIN 341 dent with the differentiation of the anterior lobe the infundibular anlage of the posterior lobe loses its cavity, but the walls of the infundibulum persist as its solid, permanent stalk. The lobe enlarges and its cells are differentiated into a diffuse tissue resembling neuroglia. About the two lobes of the hypophysis the surrounding mesenchyme develops a connective tissue capsule. Caudal to the infundibulum in the floor plate are developed in order the tuber cinereum and the mammillary recess (Figs. 341, 344 and 346). The lateral walls of the latter thicken and give rise to the paired mammillary bodies. The third ventricle lies largely in the diencephalon and is at first relatively broad. Owing to the thickening of its lateral walls it is compressed until it forms Mesencephalon Diencephalon Pallium : | Mammillary body ‘i | # ot \ Hy pophysis ne - \ Optic stalk Lobus olfactorius Fic. 344.—Lateral view of the fore- and mid-brains of a 10.2 mm. embryo (His). a narrow, vertical cleft. In a majority of adults the thalami are approximated, fuse, and form the massa intermedia or commissura mollis, which is encircled by the cavity of the ventricle. The Telencephalon.—This is the most highly differentiated division of the brain (Fig. 344). The primitive structures of the neural tube can no longer be recognized, but the telencephalon is regarded as representing greatly expanded alar plates and is, therefore, essentially a paired structure. Each of the paired out- growths expands cranially, dorsally, and caudally, and eventually overlies the rest of the brain (Figs. 344, 345 and 346). The telencephalon is differentiated into the corpus striatum, rhinencephalon, and pallium (primitive cortex of cerebral 342 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM hemisphere). The median lamina between the hemispheres lags behind in its development and thus there is formed the great longitudinal fissure between the hemispheres. The lamina is continuous caudally with the roof plate of the dien- cephalon; cranially it becomes the lamina terminalis, the cranial boundary of the third ventricle (Figs. 332 and 342). Chorioid Plexus of the Lateral Ventricles—It will be remembered that the chorioid plexus of the third ventricle develops in the folds of the roof plate of the diencephalon. Similarly the thin, median wall of the pallium at its junction with the wall of the diencephalon is folded into the lateral ventricle. A vascular Fissura prima Chorioid plexus of lat. ventricle — Corpus striatum if Hippocampus Pallium —\ Me Roof plate Pineal body Superior colliculus Mesencephalon Fic. 345.—The fore-brain and mid-brain of an embryo 13.6 mm. long seen from the dorsal surface. The pallium of the telencephalon is cut away, exposing the lateral ventricle (His). plexus, continuous with that of the third ventricle, grows into this fold, and pro- jects into the lateral ventricle of either side (Figs. 345 and 347). The fold of the pallial wall forms the chorioidal fissure and the vascular plexus is the chorioid plexus of the lateral ventricle. This is a paired structure and with the plexus of the third ventricle forms a T-shaped figure, the stem of the Y overlying the third ventricle, its curved arms projecting into the lateral ventricles just caudal to the interventricular foramen. Later, as the pallium extends, the chorioid plexus of the lateral ventricles and the chorioidal fissures are extensively elongated into the temporal lobe and inferior horn of the lateral ventricle (Fig. 348). THE BRAIN 343 The interventricular foramen (of Monro) is at first a wide opening (Fig. 343), but is later narrowed to a slit, not by constriction but because its boundaries grow more slowly than the rest of the telencephalon (Fig. 347). Diencephalon Mesencephalon Pallium poy Corpus mammillare Pars ant. olf. lobe aa Tuber cinereum Pars post. olf. lobe Infundibulum Optic stalk Fic. 346.—Lateral view of the fore-brain and mid-brain of a 13.6 mm. embryo (His). Lateral ventricle Chorioid plexus of lateral ventricle Thalamus Corpus striatum + Third ventricle Fic. 347.—Transverse section through the fore-brain of a 16 mm. embryo showing the early develop- ment of the chorioid plexus and fissure (His). The third ventricle extends some distance into the caudal end of the telen- cephalon and laterally in this region the optic vesicles develop. Into each optic stalk extends the optic recess (Fig. 343). 344 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM Falx Fic. 348.—A transverse section through the telencephalon of an 83 mm. fetus (aiter His). Th, Thalamus; Cs, corpus striatum; /,f., hippocampal fissure; fa, marginal gray seam; fi, edge of white substance. Chorioid fissure Ili p pocam pus Sup. colliculus Nucleus caudalus Inf. colliculus Internal capsule Cerebellum ——— Olfactory lobe Medulla oblongata Fic. 349.—Lateral view of the brain of a 53 mm. fetus. The greater part of the pallium of the right cerebral hemisphere has been removed, leaving only that covering the lenticular nucleus, and exposing the internal capsule, caudate nucleus and hippocampus (His). THE BRAIN 345 The corpus striatum is developed as a thickening in the floor of each cerebral hemisphere. It is already prominent in embryos of six weeks (13.6 mm.) bulg- ing into the lateral ventricle (Figs. 345 and 347). It is in line caudally with the thalamus of the diencephalon and in development is closely connected with it, although the thalamus always forms a separate structure. The corpus striatum elongates as the cerebral hemisphere lengthens, its caudal portion curving around to the tip of the inferior horn of the lateral ventricle and forming the slender tail of the caudate nucleus (Fig. 349). The thickening of the corpus striatum is due Anterior horn ~— Lenticular nucleus Ant. columns of fornix Internal capsule Nucleus caudatus Interventricular foramen Third ventricle Thalamus Chorioid plexus of ; Hip pocampus lat. ventricle Posterior horn Fic. 350.—Horizontal (coronal) section through the fore-brain of a 160 mm. fetus (His). to the active proliferation of cells in the ependymal layer which form a prominent mass of mantle layer cells. Nerve fibers to and from the thalamus to the cere- bral cortex course through the corpus striatum as lamine which are arranged in the form of a wide V, open laterally, when seen in horizontal sections. This V- shaped tract of white fibers is the znternal capsule, the cranial limb of which partly separates the corpus striatum into the caudate and lenticular nuclei (Fig. 350). The caudal limb of the capsule extends between the lenticular nucleus and the thalamus. 346 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM The thalamus and corpus striatum are separated by a deep groove until the end of the third month (Fig. 347). As the structures enlarge, the groove between them disappears and they form one continuous mass (Fig. 350). According to some investigators, there is direct fusion between the two. The Rhinencephalon or Olfactory Apparatus.—This is divided into a basal portion and a pallial portion. The basal portion consists: (1) in a ventral and cranial evagination (pars anterior), formed mesial to the corpus striatum, which is the anlage of the olfactory lobe and stalk (Fig. 346). This receives the olfactory fibers and its cells give rise to olfactory tracts. The tubular stalk connecting the olfactory lobe with the cerebrum loses its lumen. (2) Caudal to the anlage of the olfactory lobe a thickening of the brain wall develops (pars posterior) which ex- tends mesially along the lamina terminalis and laterally becomes continuous with the tip of the temporal lobe (Fig. 346). This thickening constitutes the anterior perforated space and the parolfactory area of the adult brain (Fig. 356). The pallial portion of the rhinencephalon is termed the archipallium because it forms the entire primitive wall of the cerebrum, a condition which is permanent in fishes and amphibia. Later, when the neopallium, or adult cortex, arises, the archipallium forms a median strip of the pallial wall curving along the dorsal edge of the chorioidal fissure from the anterior perforated space around to the tip of the temporal lobe, where it is again connected with the basal portion of the rhinen- cephalon. The archipallium differentiates into the hippocampus (Figs. 345 and 349), a portion of the gyrus hippocampi, and into the gyrus dentatus. It resembles the rest of the cerebral cortex in the arrangement of its cells. The infolding of the hippocampus produces the hippocampal fissure. : The Commissures of the Telencephalon.—The important commissures are the corpus callosum, fornix, and anterior commissure. The first is the great trans- verse commissure of the neopallium, or cerebral cortex, while the fornix and an- terior commissure, smaller in size, are connected with the archipallium of the rhinencephalon. The commissures develop in relation to the lamina terminalis, crossing partly in its wall and partly in fused adjacent portions of the median pallial walls. Owing to the fusion of the pallial walls dorsal and cranial to it, the lamina terminalis thickens rapidly in stages between 80 and 150 mm. (C R) (Streeter). “It [the lamina terminalis] is distended dorsalward and antero- lateralward through the growth of the corpus callosum, the shape of which is determined by the expanding pallium.” Between the curve of the corpus callo- sum and the fornix the median pallial walls remain thin and membranous, and constitute the sepium pellucidum of the adult. The walls of this septum THE BRAIN 347 enclose a cavity, the so-called fifth ventricle, or space of the septum pellucidum (Fig. 351). The fornix takes its origin early, chiefly from cells in the hippocampus. The fibers course along the chorioidal side of the hippocampus cranially, pass- ing dorsal to the foramen of Monro (Fig. 351 A). In the cranial portion of the Corpus callosum Body of fornix Hippocampal commissure Anterior commissure Chorioid fissure Ant. pillar of fornix Thalamus B Body of fornix Hippocampal commissure Septum pellucidum p p Corpus callosum Ant. com missure Thalamus Ant. pillar of fornix Fic. 351.—Two stages in the development of the cerebral commissure. (Based on reconstructions by His and Streeter.) A, Median view of the right hemisphere of an 83 mm. fetus; B, the same of a 120 mum. fetus. lamina terminalis fibers are given off to, and received from, the basal portion of the rhinencephalon. In this region, fibers crossing the midline form the hippocampal commissure. Other fibers, as the diverging anterior pillars of the fornix, curve ventrally and end in the mammiilary body of the hypothalamus. The commissure of the hippocampus, originally cranial in position, is carried caudalward with the caudal extension of the corpus callosum (Fig. 351 B). 348 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM The fibers of the anterior commissure cross in the lamina terminalis ventral to the hippocampal commissure. They arise in a cranial and a caudal division. The fibers of the former take their origin from the olfactory stalk and the adjacent cortex. The fibers of the caudal division pass ventrally about the corpus striatum, between it and the cortex, and may be derived from one or both of these regions. The corpus callosum appears cranial and dorsal to the hippocampal com- missure in the roof of the thickened lamina terminalis (Fig. 351 A). Through Lobus parietalis Lateral jissure Lobus frontalis Lobus occipitalis Lobus temporalis Cerebellum Pons M yelenceph- alon 4 ae ees Spinal cord é \ Fic. 352.—Lateral view of the brain of a 90 mm. fetus (His). its fibers, which arise from neuroblasts in the wall of the neopallium (cerebral cor- tex), nearly all regions of one hemisphere are associated with corresponding regions of the other. With the expansion of the pallium, the corpus callosum is extended cranially and caudally by the development of interstitial fibers. The fibers first found in the corpus callosum arise in the median wall of the hemispheres. In fetuses of 150 mm. (C R) (five months) this great commissure is a conspicuous structure and shows the form which is characteristic of the adult (Fig. 351 B). THE BRAIN 349 The Form of the Cerebral Hemispheres.—When the telencephalon expands cranially, caudally, and at the same time ventrally, four lobes may be distin- guished (Fig. 352): (1) a cranial frontal lobe; (2) a dorsal parietal lobe ; (3) a caudal occipital lobe; and (4) a ventro-lateral temporal lobe. The ventricle extends into each of these regions and'forms respectively the anterior horn, the body, the posterior horn, and the inferior horn of the lateral ventricle. The surface extent of the cerebral wall, the thin, gray cortex, increases more rapidly than the un- derlying, white medullary layer. As a result the cortex is folded, producing con- volutions between which are depressions, the fissures and sulci. The chorioidal Jjissure is formed, as we have seen (p. 342), by the ingrowth of the chorioid plexus. cerebrum Corpora quadrigemina Impression of thalamus Hemisphere of Temporal lobe cerebellum Vermis cerebelli Lateral recess of ventricle fourth XN 7 Fasciculus gracilis ial Medulla oblongata Fic. 353.—Dorsal view of the brain from a 100 mm. fetus (Kollmann). During the third month the hippocampal fissure develops as a curved infolding along the median wall of the temporal lobe. Internally the infolded cortex forms the hippocampus (Figs. 345 and 349). The lateral fissure (of Sylvius) makes its appearance also in the third month (Fig. 352), but its development is not com- pleted until after birth. The cortex overlying the corpus striatum laterally de- velops more slowly than the surrounding areas and is thus gradually overgrown by folds of the parietal and frontal lobes (fronto-parietal operculum) and of the temporal lobe (temporal operculum). The area thus overgrown is the imsula (island of Reil) and the depression so formed is the lateral fissure (of Sylvius) (Fig. 355). Later, frontal and orbital opercula are developed ventro-laterally from the 350 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM Insula Median olfactory Lat. olfactory gyrus gyrus Middle olfactory gyrus Diagonal gyrus Gyrus ambiens Gyrus semilunaris Cerebellum Oliva Fic. 354.—Ventral view of the brain of a 100 mm. fetus, showing development of the rhinencephalon (Kollmann), Sulcus postcentralis Sulcus centralis | Lobus parietalis superior Inferior Supra- frontal marginal sulcus and an- ae Posi. Ascend- ramus ing of lateral ramus Jissure Lateral fissure (Sylviz) Middle _f temporal } sulcus Temporal Occipital lobe pole Superior temporal gyrus Middle temporal gyrus Fic. 355.—Lateral view of the right cerebral hemisphere from a seven months’ fetus (Kollmann). frontal lobe. These are not approximated over the insula until after birth. The frontal operculum is included between the anterior limbs of the Sylvian fissure, and the extent of its development, which is variable, determines the form of these limbs. THE BRAIN 351 In fetuses of six to seven months four other depressions appear which later form important landmarks in the cerebral topography. These are: (1) the cen- tral sulcus, or fissure of Rolando, which forms the dorso-lateral boundary line between the frontal and parietal lobes (Fig. 355); (2) the parieto-occi pital fissure, which, on the median wall of the cerebrum, is the line of separation between the occipital and parietal lobes (Fig. 356); (3) the calcarine fissure, which includes between it and the parieto-occipital fissure the cuneus and marks the position of the visual area of the cerebrum; (4) the collateral fissure on the ventral surface of the temporal lobe, which produces the inward bulging on the floor of the Corpus callosum Sulc. corp. callost Gyrus cinguli Splenium Paricto-occipital fissure Space of septum pellu- cidum Rostral lamina Parol- factory area Cuneus Cal- - carine eo jissure Olfactory lobe Fissura rhinica Optic nerve Temporal lobe Fic. 356.—Median surface of the right cerebral hemisphere from a seven months’ fetus (Kollmann). posterior horn of the ventricle known as the collateral eminence. The calcarine fissure also affects the internal wall of the ventricle, causing the convexity termed the calcar avis (hippocampus minor). Simultaneously with the development of the collateral fissure appear other shallower depressions known as sulci. These have a definite arrangement and with the fissures mark off from each other the various functional areas of the cerebrum. The surface convolutions between the depressions constitute the gyri and lobules of the adult cerebrum. Histogenesis of the Cerebral Cortex.—In the wall of the pallium are differ- entiated the three primitive zones typical of the neural tube: the ependymal, 352 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM mantle, and marginal layers. During the first two months the cortex remains thin and differentiation is slow. At eight weeks neuroblasts migrate from the ependymal and mantle zones into the marginal zone and give rise to layers of pyramidal and other cells typical of the cerebrum. The differentiation of these layers is most active during the third and fourth months, but probably continues until after birth (Mellus, Amer. Jour. Anat., vol. 14, 1912). From the fourth month on, the cerebral wall thickens rapidly, owing to the development of (1) the fibers from the thalamus and corpus striatum; (2) of endogenous fibers from the neuroblasts of the cortex. The fibers form a white, inner, medullary layer sur- rounded by the gray cortex. Myelination begins shortly before birth (Flechsig), but some fibers may not acquire their sheaths until after the twentieth year. As the cerebral wall increases in thickness the size of the lateral ventricle becomes relatively less, its lateral diameter especially being decreased. Anomalies.—Defects involving the neural tube may give rise to various monstrous conditions, e. g., cyclopia, acrania. In spina bifida, a sac-like protrusion of the cord, or its membranes, extends through a cleft in the vertebral column. se CHAPTER XIII THE PERIPHERAL NERVOUS SYSTEM THE nerves, ganglia, and sense organs constitute the peripheral nervous system. The peripheral nerves consist of bundles of myelinated and unmyelin- ated nerve fibers and aggregations of nerve cells, the ganglia. The fibers are of two types: afferent fibers, which carry sensory impulses to the central nervous system, and efferent fibers, which carry effective impulses away from the nervous centers. The peripheral efferent fibers of both brain and spinal cord take their origin from neuroblasts of the basal plate. Typically they emerge ventro-later- ally from the neural tube. Those arising from the spinal cord take origin in the mantle layer, converge, and form the ventral roots of the spinal nerves. The efferent fibers of the brain take origin from more definite nuclei and constitute the motor or effector portions of the cerebral nerves. The peripheral afferent fibers originate from nerve cells which lie outside the neural tube. Those sensory nerve cells related to the spinal cord . IX XxX-XI . t and to the brain stem caudal to the \ eee otic vesicle are derived from the gang- lion crest, the origin of which has been described (Chapter X, p. 304). Bridge A. SPINAL NERVES The spinal nerves are segment- ally arranged and each consists of : y 8 : Fic. 357.—Reconstruction of an embryo of 4 dorsal and ventral roots, spinal gang- mm., showing the development of the cerebrospinal nerves (Streeter), XX 17. Cr., z., etc., cervical lion, and nerve trunks. In embryos : spinal nerves. of 4 mm. the ventral roots are already developing as outgrowths of neuroblasts in the mantle layer of the spinal cord (Fig. 357). The spinal ganglia are represented as enlargements along the gang- lion crest and are connected by cellular bridges. In 7 mm. embryos (five weeks old) the cells of the spinal ganglia begin to develop centrally directed processes which enter the marginal zone of the cord as the dorsal root fibers (Fig. 358). These fibers course in the dorsal funiculi and 23 353 354 THE PERIPHERAL NERVOUS SYSTEM eventually form the greater part of them. Perpiheral processes of the ganglion cells join the ventral root fibers in the trunk of the nerve (Fig. 360). At 10mm. (Fig. 359) the dorsal root fibers have elongated and the cellular bridges of the ganglion crest between the spinal ganglia have begun to disappear. In transverse sections at this stage (Fig. 325 and 350) the different parts of a spinal nerve may be seen. The trunk of the nerve just ventral to the union of the dorsal and IV IX-X-XI gang. crest Ophthal. div. Sup. max. div. M. masticatorius 1 te] | Cy. petros. fe NV. laryng. sup. Gang. nodos. Inf. max. div. S. I. Fic. 358.—Reconstruction of a 6.9 mm. embryo, showing the development of the dorsal root fibers from the spinal and cerebral ganglia (Streeter). X 16.7. ventral roots gives off laterally the dorsal, or posterior ramus, the fibers of which supply the dorsal muscles. The ventral ramus continuing gives off mesially the ramus communicans to the sympathetic ganglion and divides into the lateral and ventral (anterior) terminal rami. The efferent fibers of these rami supply the muscles of the lateral and ventral body wall, and the afferent fibers end in the integument of the same regions. SPINAL NERVES 355 At the points where the anterior and lateral terminal rami arise, connecting loops may extend from one spinal nerve to another. Thus in the cervical region superficial and deep nerve plexuses are formed. The deep cervical plexus forms the ansa hypoglossi and the phrenic nerve (Fig. 359). Gang. Ba oe p pte ed IX Cerebellum | N.VI ' of | 'Gang. petrosum H eee ae Gang. radicis n.X N.III~ NV. hypoglossus N.IV-- a en, LEG. N. fronialis~ _ DAS on 4 é -~ N.XI —Gang. nodos. ____N. desc. cerv. __ Rami hyoid. (Ansa hypoglossi) N. Musculocutan. N. axillaris sei phrenicus - iN. medianus N. radialis NV. nasociliaris ~~ N. maxillaris ~ NV. mandibularis “ Gang. geniculalum ~~ N. chorda tympani’ Cor" ~~ N, ulnaris a ITh Diaphragma ~~ He par I Co, NV. tibialis NV. peroneus ~ R. posterior Tubus digest. “4 : oster p R. terminalis lateralis IS. ! eae R. terminalis anterior N. femoral : i ETL. N. obturator : Mesonephros Nn. ilioing. et hypogastr. Fic. 359.—Reconstruction of the nervous system of a 10 mm. embryo (Streeter). XX 12. The Brachial and Lumbo-sacral Plexuses-—The nerves supplying the arm and leg also unite to form plexuses. In embryos of 10 mm. (Fig. 359) the trunks of the last four cervical nerves and of the first thoracic are united to form a flat- tened plate, the anlage of the brachial plexus. From this plate nervous cords extend into the intermuscular spaces and end in the premuscle masses. The developing skeleton of the shoulder splits the brachial plexus into dorsal and 356 THE PERIPHERAL NERVOUS SYSTEM ventral lamine. From the dorsal lamina arise the musculocutaneous, median, and ulna nerves; from the ventral lamina, the axillary and radial nerves. In 10 mm. embryos the lumbar and sacral nerves which supply the leg unite in a plate-like structure, the anlage of the lumbo-sacral plexus (Fig. 359). The plate is divided by the skeletal elements of the pelvis and femur into two lateral and two median trunks. Of the cranial pair the lateral becomes the femoral nerve; the median, the obturator nerve. The caudal pair constitute the sciatic nerve; the lateral trunk is the peroneal nerve, and the median trunk is the “bial. Dorsal root Marginal layer Ependymal layer VC) Mantle layer Somatic sensory neurone Visceral sensory neurone. Spinal cor Visceral motor neurone Somatic motor neurone Dorsal ramus. Lat. terminal division Ventral terminal division of spinal nerve e » Ramus communicans Sympathetic ganglion Fic. 360.—Transverse section of a 10 mm. embryo showing the spinal cord, spinal nerves and their functional nervous components. Diagrammatic. Save for the neurones from the special sense organs (nose, eye, and ear) which form a special sensory group, the neurones of the peripheral nerves, both spinal and cerebral, fall into four functional groups (Fig. 360). (1) Somatic afferent, or general sensory, with fibers ending in the integument of the body wall. (2) Visceral afferent or sensory, with fibers ending in the walls of the viscera. (3) Somatic efferent or motor, with fibers ending on voluntary muscle fibers. (4) Visceral efferent or motor: (a) with fibers ending about sympathetic ganglion cells, which in turn control the smooth muscle fibers of the viscera and blood vessels (spinal nerves); or (b) with fibers ending directly on visceral muscle. fibers (mixed cerebral nerves). THE CEREBRAL NERVES 357 B. THE CEREBRAL NERVES The cerebral nerves of the human brain are twelve in number. They differ from the spinal nerves: (1) in that they are not segmentally arranged, and (2) in that they do not all contain the same types of nervous components. Classed according to the functions of their neurones they fall into three groups: SPECIAL SoMATIC SENSORY. SomATIcC Motor oR EFFERENT. VISCERAL SENSORY AND Motor. I. Olfactory. III. Oculomotor. V. Trigeminal. II. Optic. IV. Trochlear. VII. Facial. VIII. Acoustic. VI. Abducens. IX. Glossopharyngeal. XII. Hypoglossal. X. Vagus complex, including XI. Spinal Accessory. It will be seen (1) that the nerves of the first group are purely sensory, corresponding to the general somatic afferent neurones of the spinal nerves; (2) that the nerves of the somatic motor group are purely motor and correspond to the somatic efferent or motor neurones of the spinal nerves; (3) that the nerves of the third group are of mixed function and correspond to the visceral components of the spinal nerves. I. THE SPECIAL SOMATIC SENSORY NERVES 1. The Olfactory Nerve, though purely sensory, has no ganglion. Its nerve cells lie at first in the olfactory epithelium of the nose and are of the bipolar type (fourth week). From these cells periph- eral processes develop and end directly : - “Olfactory tract 1 ithe- at the surface of the olfactory epi abe at ol lium (Fig. 361). Central processes grow -—Glomerulus toward the olfactory lobe and form the \\Cribriform plate - Olfactory nerve fiber : - - 4 ri ebydtt -- Olfactory epithelium contact with the dendrites of the mitral = fe f ? Fic. 361—Diagram of the relations of the fibers in the olfactory nerve. strands of the olfactory nerve. They end Lb, in the glomeruli of the olfactory bulb in cells, or olfactory neurones of the second order. Some olfactory cells migrate from the epithelium, with which, however, they retain peripheral connections. Such bipolar cells, found along the entire course of the nerve, resemble ordinary dorsal ganglion cells. The olfactory nerve fibers are peculiar in that they remain unmyelinated. Nerve fibers from the epithelium of the vestigial vomero-nasal organ (of Jacobson) also end in the olfactory bulb. When the ethmoidal bone of the cranium is developed, its cartilage, as the cribriform plate, forms around the strands of the olfactory nerve. 358 THE PERIPHERAL NERVOUS SYSTEM The ganglionated 2. terminalis courses in close association with the olfactory nerve. Its fibers end in the epithelium of the vomero-nasal organ and of the nose. Although evidently a distinct nerve its significance is obscure. 2. The Optic Nerve is formed by fibers which take their origin from neuro- blasts in the nervous layer of the retina. The retina is differentiated from the wall of the fore-brain and remains attached to it by the optic stalk (Fig. 343), hence the optic nerve is not a true peripheral nerve, but belongs to the central system of tracts. The neuroblasts from which the optic nerve fibers develop constitute the ganglion cell layer of the retina (Fig. 381). During the sixth and seventh weeks these cells give rise to central processes which form a nerve fiber layer on the inner side of the retina. The optic fibers converge to the optic stalk and grow through its wall back to the brain. The cells of the optic stalk are converted into a neuroglia framework and the cavity is obliterated. In the floor of the fore-brain, at the boundary between telencephalon and diencephalon, the fibers from the median half of each retina at about the end of the second month cross to the opposite side, and this decussation constitutes the optic chiasma (from Greek letter ¥ or “‘chi”). The crossed and uncrossed fibers constitute the optic tract which rounds the cerebral peduncles laterally and dorsally (Fig. 354). Eventually the optic fibers end in the lateral geniculate body, thalamus, and superior colliculus. Efferent fibers, terminating in the inner reticular layer of the retina, are also present. In certain fishes where their function has been studied these fibers resemble visceral efferent components (Arey, Jour. Comp. Neurol., vol. 26, 1916). 8. The Auditory Nerve, or N. Acusticus, is formed by fibers which grow from the cells of the acoustic ganglion. The origin of these cells is unknown, though they appear in 4 mm. embryos just cranial to the otic vesicle (Fig. 358). The cells become bipolar, central processes uniting the ganglion to the tuberculum acusticum of the myelencephalon and peripheral fibers connecting it with the wall of the otocyst. The acoustic ganglion is differentiated into the vestibular and spiral ganglia (Fig. 362). Its development has been studied by Streeter (Amer. Jour. Anat., vol. 6, 1907). The ganglion elongates and is subdivided into superior and inferior portions in 7 mm. embryos. The superior part supplies nerves to the utriculus and to the ampulle of the anterior and lateral semicircular canals. It forms part of the vestibular ganglion of the adult. Part of the inferior portion supplies nerves to the sacculus and to the ampulla of the posterior semicircular canal, and this portion, together with the pars superior, constitutes the vestibular ganglion. The greater part of the pars inferior is, however, differentiated into the THE CEREBRAL NERVES 359 aN. vestib..-- - - >-=.Pars. sup. 4mm. 7mm... --Pars. inf. Pars. sup. Pars. sup. ; ; sf -- N. vestib. - Pars. inf. ae N Ret Pars. inf. nm t t ‘ SS 9mm. —— “SN. coch. -- Gang. spirale R. amp. sup. -R. amp. lat. “R. utric. R. amp. sup. 4 6 -R. amp. lat. 30 mm. MEDIAN VIEW LATERAL VIEW Fic. 362.—The development of the acoustic ganglia and nerves. The vestibular ganglion is finely stippled, the spiral ganglion coarsely stippled (Streeter). Spiral ganglion, the peripheral fibers of which innervate the hair cells of the spiral organ (of Corti) in the cochlea. The spiral ganglion appears in 9 mm. embryos and conforms to the spiral turns of the cochlea, hence its name. Its central nerve 360 THE PERIPHERAL NERVOUS. SYSTEM fibers form the cochlear division of the acoustic nerve. This is distinctly sepa- rated from the central fibers of the vestibular ganglion which constitute the ves- tibular division of the acoustic nerve, the fibers of which are not auditory in func- tion. The pars inferior of the vestibular ganglion becomes closely connected with the n. cochlearis, and thus in the adult it appears as though the sacculus and posterior ampulla were supplied by the cochlear nerve. Il. THE SOMATIC MOTOR NERVES The nerves of this group, consisting of the three nerves to the eye muscles and the n. hypoglossus, are purely motor nerves, the fibers of which take origin from the neuroblasts of the basal plate of the brain stem, near the midline. They are regarded as the homologues of the ventral motor roots of the spinal cord, but have lost their segmental arrangement and are otherwise modified. The nuclei of origin of these nerves are shown in Fig. 364. 12. N. Hypoglossus.—This nerve is formed by the fusion of the ventral root fibers of three to five precervical nerves. Its fibers take origin from neuroblasts of the basal plate and emerge from the ventral wall of the myelencephalon in several groups (Fig. 357). In embryos of five weeks (7 mm.) the fibers have converged ventrally to form the trunk of the nerve (Fig. 358). Later they grow cranially, lateral to the ganglion nodosum, and eventually end in the muscle fibers of the tongue (Fig. 359). The nerve in its development unites with the first three cervical nerves to form the ansa hypoglossi. Its nucleus of origin is shown in Fig. 364. That the hypoglossal is a composite nerve homologous with the ventral roots of the spinal nerves is shown: (1) by the segmental origin of its fibers; (2) from the fact that its nucleus of origin is a cranial continuation of the ventral gray column, or nucleus of origin for the ventral spinal roots; (3) from the fact that in mammalian embryos (pig, sheep, cat, etc.) rudimentary dorsal ganglia are developed, one of which at least (Froriep’s ganglion) sends a dorsal root to the hypoglossal. In human embryos Froriep’s ganglion may be present as a rudimentary structure (Figs. 359 and 363), or it may be absent and the ganglion of the first cervical nerve may also degenerate and disappear. In pig embryos Prentiss (Jour. Comp. Neurol., vol. 20, 1910) has found two and three accessory ganglia (including Froriep’s) from which dorsal roots extended to the root fascicles of the hypoglossal nerve (Fig. 121). 3. The Oculomotor Nerve originates from neuroblasts in the basal plate of the mesencephalon (Fig. 339 B). The fibers emerge as small fascicles on the ventral surface of the mid-brain in the concavity due to the cephalic flexure (Figs. 359 and 364). The fascicles converge, form the trunk of the nerve, and end in the premuscle masses of the eye. The nerve eventually supplies all of the extrinsic THE CEREBRAL NERVES 361 muscles of the eye save the superior oblique and external rectus. A branch is also supplied to the ciliary ganglion. In the chick embryo, bipolar cells migrate along the fibers of the oculomotor nerve to take part in the development of the ganglion. The ciliary ganglion of human embryos is derived entirely from the semilunar ganglion of the trigeminal nerve. 4. The Trochlear Nerve fibers take their origin from neuroblasts of the basal plate, located just caudal to the nucleus of origin of the oculomotor nerve. They are directed dorsally, curve around the cerebral aqueduct, and, crossing in its roof, emerge at the isthmus (Fig. 339 A). From their superficial origin each is directed ventrally as a slender nerve which connects with the anlage of the superior oblique muscle of the eye (Fig. 359). 6. The N. Abducens takes origin from a nucleus of cells in the basal plate of the myelencephalon, located directly beneath the fourth neuromere of the floor of the fourth ventricle (Figs. 359 and 364). The converging fibers emerge ventrally at a point caudal to the future pons, and, asa single trunk, course cranially, mesial to the semilunar ganglion, finally ending in the anlage of the external rectus muscle of the eye. Vestigial rootlets of the abducens and hypoglossal nerve tend to fill in the gap between these two nerves, according to Bremer and Elze. Il. THE VISCERAL MIXED NERVES The nerves of this group, the trigeminal, facial, glossopharyngeal, and vagus complex (vagus plus the spinal accessory), are mixed in function. The trigem- inal nerve, beside its visceral nerve components, contains also numerous somatic sensory neurones which supply the integument of the head and face. 5. The Trigeminal Nerve is largely sensory. Its semilunar ganglion is the largest of the whole nervous system and is a derivative of the ganglion crest, but very early is distinct from the other cerebral ganglia (Fig. 358). It arises later- ally at the extreme cranial end of the hind-brain. Central processes from its cells form the large sensory root of the nerve which enters the wall of the hind- brain at the level of the pontine flexure (Fig. 359). These fibers fork and course cranially and caudally in the alar plate of the myelencephalon. The caudal fibers constitute the descending spinal tract of the trigeminal nerve, which extends as far caudad as the spinal cord (Fig. 364). The peripheral processes separate into three large divisions, the ophthalmic, maxillary, and mandibular rami, and supply the integument of the head and face and the epithelium of the mouth and tongue. The motor fibers of the trigeminal nerve arise chiefly from a dorsal motor 362 THE PERIPHERAL NERVOUS SYSTEM nucleus which lies opposite the point at which the sensory fibers enter the brain wall (Fig. 364). In the embryo these fibers emerge as a separate motor root, course along the mesial side of the semilunar ganglion, and, as a distinct trunk, supply the premuscle masses which later form the muscles of mastication. From the chief motor nucleus, a line of cells extending cranially into the mesencephalon constitutes a second source of origin for motor fibers. In the adult, the motor fibers form a part of the mandibular division of the nerve. The facial, glossopharyngeal, and vagus nerves are essentially visceral in func- tion. Their sensory fibers, chiefly of the visceral type, supply the sense organs Vagus root ganglion (jugular) Accessory root ganglia Gang. nodos. ih iesan. aap: —Inter-gang. bridge XIT Fic. 363.—Reconstruction of the cerebral nerves of an embryo of 10.2 mm. (Streeter). X 16.7. of the branchial arches and viscera. These fibers originate in the ganglia of their respective nerves, and, entering the alar plate of the myelencephalon, course caudally as the solitary tract (Fig. 364). A few somatic sensory fibers, having the same origin and course in the myelencephalon, supply the adjacent integu- ment. In aquatic vertebrates, special somatic sensory fibers from the /afcral line organs join the facial, glossopharyngeal, and vagus nerves, and their ganglion cells form part of the genicu- late, petrosal, and nodose ganglia. In human embryos the organs of the lateral line are repre- sented by ectodermal thickenings or placodes which occur temporarily over these ganglia. The nervous elements supplying these vestigial organs have completely disappeared. THE CEREBRAL NERVES 363 7. The Facial Nerve is largely composed of efferent motor fibers which supply the facial muscles of expression. In 10 mm. embryos these fibers arise from a cluster of neuroblasts in the basal plate of the myelencephalon located beneath the third rhombic groove or neuromere (Fig. 364). The fibers from these cells course laterally, and emerge just mesial to the acoustic ganglion. The motor trunk then courses caudally and is lost in the tissue of the hyoid visceral arch, tissue which later gives rise to the muscles of expression (Fig. 359). The sensory fibers of the facial nerve arise from the cells of the geniculate ganglion, which are in turn derived from the ganglion crest (Streeter). This ganglion is present in 7 mm. Nucl motor. n X (ambiguus) Tractus solitarius Nucl motor n, trigemini ' Gang radicis n.X Tractus spinalis pV . MO ERGenleAuiaeeel 1 I ! ‘ ' I ‘Gang ¢ are H ‘Radix sens n.1X ! 1 Gang semilunare 1 ' ent ' ' Gang geniculatum |! Tr cerebell ob V. : ' Radix sens n VII | | (pars Intermed) + ' 1 ' 1 1 Radix sens. n.X i 1 ' ' ' Rr. mot. n.X Nucl. n. hypoglossi N. accessorius «------~-- s --N. frontalis B.-----N nasoclliatis tos | Nucl n.VI 1} ' | N abducens ' ' 1 ' 1 ' ' ' 1 t ' Lau ; t Nucl o.VII Cane spetive sas, N. maxillaris t : N. facialis Funie. ze j N. hypoglossus Portlo minor posterior = Gang. nodos. 1 andibularis 1 ' ' ) ' t m: Zz “~~ R, mot. ventr. “ R mot. lat. R. hyold * R. posterlor N. vagus Fic. 364.—Reconstruction of the nuclei of origin and termination of the cerebral nerves in an embryo of 10 mm. The somatic motor nuclei are colored red (Streeter). X 30. embryos (Fig. 358), located cranial to the acoustic ganglion. The centrally directed processes of the geniculate ganglion enter the alar plate and form part of the solitary tract. The peripheral fibers in part course with motor fibers in the chorda tympani, join the mandibular branch of the trigeminal nerve, and end in the sense organs of the tongue. Other sensory fibers form later the great superficial petrosal nerve, which extends to the spheno-palatine ganglion. The motor fibers of the facialis at first course straight laterad passing cra- nial to the nucleus of the abducens. The nuclei of the two nerves later gradually shift their positions, that of the facial nerve moving caudad and laterad, while the nucleus of the abducens shifts cephalad. As a result, the motor root of the N. oculomotorus 364 THE PERIPHERAL NERVOUS SYSTEM facial nerve in the adult bends around the nucleus of the abducens producing the genu or knee, of the former. The two together produce the rounded eminence in the floor of the fourth ventricle known as the facial colliculus. 9. The Glossopharyngeal Nerve takes its superficial origin just caudal to the otic vesicle (Figs. 358, 363 and 365). Its few motor fibers arise from neuroblasts in the basal plate beneath the fifth neuromeric groove. These neuroblasts form part of the nucleus ambiguus, a nucleus of origin which the glossopharyngeal shares with the vagus (Fig. 364). The motor fibers course laterally beneath the spinal tract of the trigeminal nerve and emerge to form the trunk of the nerve. These fibers later supply the muscles of the pharynx. The sensory fibers of the glossopharyngeal nerve arise from two ganglia, a superior, or root ganglion, and a peirosal, or trunk ganglion (Figs. 359 and 365). These fibers constitute the greater part of the nerve and divide peripherally to form the tympanic and lingual rami to the second and third branchial arches. Centrally, these fibers enter the alar plate of the myelencephalon and join the sensory fibers of the facial nerve coursing caudally in the solitary tract. 10, 11. The Vagus and Spinal Accessory.—The vagus, like the hypoglossal, is composite, representing the union of several nerves, which, in aquatic animals, supply the branchial arches (Figs. 359 and 365). The more caudal fascicles of motor fibers take their origin in the lateral gray column of the cervical cord as far back as the fourth cervical segment. These fibers emerge laterally, and, as the spinal accessory trunk (in anatomy a distinct nerve), course cephalad along the line of the neural crest (Figs. 358, 359 and 365). Other motor fibers take their origin from the neuroblasts of the nucleus ambiguus of the myelencephalon (Fig. 364). Still others arise from a dorsal motor nucleus which lies median in position. The fibers from these two sources emerge laterally as separate fascicles and join the fibers of the spinal accessory in the trunk of the vagus nerve. The accessory fibers soon leave the trunk of the vagus and are distributed laterally and caudally to the visceral premuscle masses which later form the sterno-cleido-mastoid and trapezius muscles of the shoulder (Fig. 359). Other motor fibers of the vagus supply muscle fibers of the pharynx and larynx. As the vagus is a composite nerve it has several root ganglia which arise as enlargements along the course of the ganglion crest (Figs. 359 and 365). The more cranial of these ganglia is the ganglion jugulare. The others, termed accessory ganglia, are vestigial structures and not segmentally arranged. In addition to the root ganglia of the vagus the ganglion nodosum forms a ganglion of the trunk (Fig. 365). The trunk ganglia of both the vagus and glossopharyn- THE CEREBRAL NERVES 365 geal nerves are believed to be derivatives of the ganglion crest, their cells migrat- ing ventrally in early stages. The central processes from the neuroblasts of the vagus ganglia enter the wall of the myelencephalon, turn caudalward, and, with the sensory fibers of the Vagus root ganglion (Jugular) Accessory root ganglia IX. root gang. (Superior) Gang. petros. N. tymp. XII N. laryng. sup. Gang. nodos. Sympathetic Fic. 365.—A reconstruction of the peripheral nerves in an embryo of 17.5 mm. (Streeter). X 16.7. facial and glossopharyngeal nerves, complete the formation of the solitary tract. The peripheral processes of the ganglion cells form the greater part of the vagus trunks after the separation from it of the spinal accessory fibers. The Segmentation of the Vertebrate Head.—The vertebrate head undoubtedly consists of fused segments. This was suggested to the earlier workers by the arrangement of 366 THE PERIPHERAL NERVOUS SYSTEM the branchial arches (branchiomerism), and by the discovery, in the embryos of lower ver- tebrates, of so-called head cavities, homologous with mesodermal segments. (Note also the presence of neuromeres, p. 334.) Assuming that the branchiomeres are portions of the primary head segments—and there are recent observations which tend to disprove this—their segmentation is still not com- parable to that of the trunk, for the branchial arches are formed by the segmentation of splanchnic mesoderm, tissue which in the trunk never segments. The branchial arches, therefore, represent a different sort of metamerism. Only the first three head cavities persist. These form the eye muscles, innervated by the third, fourth, and sixth cranial nerves respectively. All the remaining muscles of the head are derived from the branchiomeres. From what has been said it is evident that one cannot compare the relation of the cranial nerves to the branchiomeric muscles with the relation of a spinal nerve to its myotomic muscles. For this reason the cranial nerves furnish unreliable evidence as to the primitive number of cephalic segments. Various investigators have set this number between eight and nineteen. C. THE SYMPATHETIC NERVOUS SYSTEM The sympathetic nervous system is composed of a series of ganglia and peripheral nerves, the fibers of which supply gland cells and the smooth muscle fibers of the viscera and blood vessels. It may function independently of the central nervous system and is hence known as the eutonomic system. The sympathetic ganglion cells are derived from the cells of the ganglion crest. In fishes discrete cellular masses become detached from the spinal ganglia. At an early stage (6 to 7 mm.) in human development, on the contrary, certain cells of the ganglion crest migrate ventrally and give rise to a series of ganglia, which, in the region of the trunk, are segmentally arranged (Figs. 139 and 360). According to Kuntz (Jour. Comp. Neurol., vol. 20, 1910), the primary source of these errant cells is the neural tube, from which they migrate along both dorsal and ventral nerve roots. At 9 mm. the ganglionated cord is formed and fibers connecting the sympathetic ganglia with the spinal nerves constitute the rami communicantes (Streeter). The more peripheral ganglia (cardiac and cceliac) _and the sympathetic ganglia of the head may be found in 16 mm. embryos (Fig. 366). The cells which are to form the ganglia of the sympathetic chain migrate ventrally in advance of the ventral root fibers and take up a position lateral to the aorta. These ganglionic anlages are at first distinct, but soon unite with each other from segment to segment, forming a longitudinal cord of cells. After the formation of the primitive rami communicantes by the root fibers from the spinal nerves, centripetal processes from the sympathetic cells grow back and join the trunks of the spinal nerves. The visceral, spinal fibers later become myelinated and constitute the white rami; the sympathetic, centripetal fibers remain unmye- THE SYMPHATHETIC NERVOUS SYSTEM 367 linated and form separately the gray rami. Nerve fibers appear in the paired longitudinal cords, which were at first purely cellular, in such a manner that seg- mental masses of cells (sympathetic ganglia) become linked by fibrous, commissural cords. In the head region the sympathetic ganglia are not segmentally arranged, but are derived from cells of the cerebrospinal ganglia which migrate to a ventral oor”_A& : 1 2 ~ oe RAI rime AE aes tal iid LO “yee Fic. 366.—The sympathetic system in a 16 mm. human embryo (Streeter in Lewis and Stdhr). X 7. The ganglionated trunk is heavily shaded. The first and last cervical, thoracic, lumbar, sacral and coccygeal spinal ganglia are numbered. a., Aorta; acc., accessory nerve; car., carotid artery; cil., ciliary ganglion; coe., coeliac artery; Ht., heart; nod., nodose ganglion; of., otic ganglion; pet., petrosal ganglion; s-m., submaxillary ganglion; s.mes., superior mesenteric artery; sph.-p., sphenopalatine ganglion; s#l., splanchnic nerve; Sé., stomach. position (Fig. 365). These cells likewise give rise to nerve fibers which constitute longitudinal commissures connecting the various ganglia of the head with the ganglionated cord of the trunk region. The small cranial sympathetic ganglia are probably all derived from the anlage of the semilunar ganglion (Fig. 366). 368 THE PERIPHERAL NERVOUS SYSTEM The ciliary ganglion is related by a ramus communicans to the ophthalmic division of the trigeminal nerve and receives fibers from the oculomotor nerve. Its cells are probably derived entirely from the semilunar ganglion. The sphenopalatine, submaxillary, and otic ganglia probably take their origin from migrating cells of the semilunar ganglion, but as they are connected with the geniculate ganglion of the facial nerve, the latter may contribute to their formation. The sphenopala- tine ganglion is connected directly with the semilunar ganglion by two com- municating rami. The submaxillary ganglion is intimately related through the mandibular division of the trigeminal nerve to the semilunar ganglion, while the otic ganglion is united to the latter by a plexus and is related to the glossopharyn- geal nerve through its tympanic branch. The cervical ganglia lose their segmental arrangement and represent the fusion of from two to five ganglia of the cervical and upper thoracic region. The more distally located prevertebral ganglia (of the cardiac, coeliac, hypogastric, and pelvic plexuses) are derived from cells of the neural crest which migrate to a greater dis- tance ventrally (Fig. 366). The visceral ganglia (of the myenteric and submucous plexuses), and the prevertebral cardiac plexus as well, are derived by Kuntz chiefly from migratory cells from the hind-brain and from the vagus ganglia. The sympathetic nerve cells give rise to axons and dendrites, and are thus typically multipolar cells. Their axons possess a neurilemma sheath, but remain unmyelinated. D. CHROMAFFIN BODIES: SUPRARENAL GLAND Certain cells of the sympathetic ganglia do not form nerve cells, but are transformed into peculiar gland cells which produce an internal secretion. The secretion formed by these cells causes them to stain brown when treated with chrome salts, hence they are called chromaffin cells. Cells of this type derived from the ganglionated cord of the sympathetic system give rise to structures known as chromaffin bodies. Chromaffin derivatives of the cceliac plexus, together with mesenchymal tissue, form the anlage of the swprarenal gland, an organ which reaches a relatively large size in human embryos (Fig. 232). The Chromaffin Bodies of the ganglionated cords are rounded cellular masses partly embedded in the dorsal surfaces of the ganglia (Fig. 367). At birth they may attain a diameter of 1 to 1.5mm. In number they vary from one to several for each ganglion. Similar chromaffin bodies may occur in all the larger sympathetic plexuses. The largest of these structures found in the abdominal sympathetic plexuses are CHROMAFFIN BODIES: SUPRARENAL GLAND 369 the aortic chromaffin bodies (of Zuckerkandl). These occur on either side of the inferior mesenteric artery, ventral to the aorta and mesial to the metanephros. At birth they attain a length of 9 to 12 mm. and are composed of cords of chromaf- fin cells intermingled with strands of connective tissue, the whole being sur- rounded by a connective tissue capsule. After birth the chromaffin bodies de- generate, but do not disappear entirely. Glomus Carolicum.—Associated with the intercarotid sympathetic plexus is a highly vascular chromaffin body known as the carotid gland. Its anlage has been first observed in 20 mm. embryos. The Suprarenal Gland is de- veloped from chromaffin tissue which becomes its medulla, and from meso- dermal tissue which gives rise to its cortex. In an embryo of 6 mm. the anlage of the cortex is present, ac- cording to Soulié, and is derived from ingrowing buds of the ccelomic epi- thelium. At 8 mm. the glands are definite organs and at 9 mm. their vascular structure is evident. The cellular elements of the cortex are at first larger than the chromaffin cells which give rise tou the medulla. The anlages of the glands form projections in the dorsal wall of the coclom be- tween the mesonephros and mesen- z Fic. 367.—Section through a chromaffin body tery (Figs. 221, 232 and 233). in a 44 mm. human fetus (after Kohn). X 450. The chromaffin cells of the med- __ p, Mother chromaffin cells; sy, sympathetic cells; b, blood vessel. ulla are derived from the cceliac plexus of the sympathetic system. In embryos of 15 to 19 mm. (Fig. 368) masses of these cells begin to migrate from the median side of the suprarenal anlage to a central position, and later surround the central vein which is present in embryos of 23 mm. The primitive chromaffin cells are small and stain intensely. They con- tinue their immigration until after birth. The differentiation of the cortex into its three characteristic layers is not completed until between the second and third years. The inner reticular zone is formed first, next the fasciculate zone, and last the glomerular zone. 24 370 THE PERIPHERAL NERVOUS SYSTEM When the cells of the medulla begin to produce an internal secretion they give the chrome reaction. By using extract of the aortic bodies, which are en- tirely composed of chromaffin cells, Bied] and Wiesel have proved that its effect, like that of adrenalin, is to increase the blood pressure. The logical conclusion is that the effect of adrenalin, an extract of the suprarenal glands, is due to an internal secretion produced by the chromaffin cells of the suprarenal medulla. Fic. 368.—Transverse section through right suprarenal gland of a 15.5 mm. human embryo (after Bryce). sy, Sympathetic cells; sy’, groups of chromaffin sympathetic cells migrating into the suprarenal gland. Portions of the suprarenal anlage may be separated from the parent gland and form accessory supravenals. As a rule, such accessory glands are composed only of cortical sub- stance; they may migrate some distance from their original position, accompanying the genital glands. In fishes the cortex and medulla persist normally as separate organs. E. DEVELOPMENT OF THE SENSE ORGANS The sense cells of primitive animals (e. g., worms) are ectodermal in origin and position. Only those of the vertebrate olfactory organ have retained this primitive relation. During phylogeny the cell-bodies of all other such primary sensory neurones migrated inward to form the dorsal ganglion (Parker), hence ‘ DEVELOPMENT OF THE SENSE ORGANS 371 their peripheral processes either end freely in the epithelium or appropriate new cells to serve as sensory receptors (taste, hearing). The nervous structures of the sense organs consist of the general sense organs of the integument, muscles, tendons, and viscera, and of the special sense organs which include the taste buds of the tongue, the olfactory epithelium, the retina, optic nerve and lens of the eye, and the epithelial lining of the ear labyrinth. I, GENERAL SENSORY ORGANS Free nerve terminations form the great majority of all the general sensory organs. When no sensory corpuscle is developed, the neurofibrils of the sensory nerve fibers separate and end among the cells of the epithelia. Lamellated corpuscles first arise during the fifth month as masses of meso- dermal cells clustered around a nerve termination. These cells increase in num- ber, flatten out, and give rise to the concentric lamelle of these peculiar structures. In the cat these corpuscles increase in number by budding. The tactile corpuscles, according to Ranvier, are developed from mesenchymal cells and branching nerve fibrils during the first six months after birth. I. TASTE BuDS The anlages of the taste buds appear as thickenings of the lingual epithelium in 110 mm. (C H) fetuses (Graberg). The cells of the taste bud anlage lengthen and later extend to the surface of the epithelium. They are differentiated into the sensory taste cells, with modified cuticular tips, and into supporting cells. The taste buds are supplied by nerve fibers of the seventh, ninth, and tenth cerebral nerves; the fibers branch and end in contact with the periphery of the taste cells. In the fetus of five to seven months taste buds are more widely distributed than in the adult. They are found in the walls of the vallate, fungiform, and foliate papille of the tongue, on the under surface of the tongue, on both surfaces of the epiglottis, on the palatine tonsils and arches, and on the soft palate. After birth many of the taste buds degenerate, only those on the lateral walls of the vallate and foliate papille, on a few fungiform papillz, and on the laryngeal sur- face of the epiglottis persisting. Il. THE OLFACTORY ORGAN The olfactory epithelium arises as paired thickenings or placodes of the cranial ectoderm (Fig. 369 A). The placodes are depressed to form the olfactory pits, or fosse, about which the nose develops (Fig. 89). 372 THE PERIPHERAL NERVOUS SYSTEM In embryos of 4 to 5 mm. (Fig. 369) the placodes are sharply marked off from the surrounding ectoderm as ventro-lateral thickenings near the top of the head. They are flattened and begin to invaginate in embryos of 6to7mm. In 8mm. embryos the invagination has produced a distinct pit, or fossa, surrounded every- where save ventrally by a marginal swelling. The later development of the olfactory organ is associated with that of the face. It will be remembered (cf. p. 145) that the first branchial arch forks into the maxillary and mandibular processes. Dorsal to the oral cavity is the fronto- Fore-brain Olfactory placode Olfactory placode Vomero-nasal organ Telencephalon Nasal fossa Lat. nasal process Median nasal process Med. nasal process Nasal fossa 4 Maxillary process Epithelial plate Frc. 369.—Sections through the olfactory anlages of human embryos. A, 4.9 mm. (X 20); B, 6.5 mm. (X 13); C, 8.8mm. (X 13); Dand £,10mm. (A, Band C from Kiebel and Elze.) nasal process of the head, lateral to it the maxillary processes, and ventral to it are the mandibular processes (Fig. 97). With the development of the nasal pits the fronto-nasal process is divided into paired lateral nasal processes and a single median frontal process, from which are differentiated later the median nasal proc- esses, or processus glotuilares (Fig. 370). The nasal pits are at first grooves, each bounded mesially by the median frontal process and laterally by the lateral nasal process and the maxillary process (Fig. 370 A). The fusion of the maxillary processes with the ventro-lateral ends of the median frontal process converts the DEVELOPMENT OF THE SENSE ORGANS 373 nasal grooves into blind pits or fosse, shutting them off from the mouth cavity (Fig. 370). Thus in embryos of 10 to 12 mm. the nasal fossa has but one opening, the external naris, and is separated from the mouth cavity by an ectodermal plate (Fig. 369 D, E). The ventro-lateral ends of the median frontal process enlarge and become the median nasal processes which fuse with the lateral nasal processes and re- duce the size of the external nares (Fig. 370 B). Externally, the nares are now bounded ventrally by the fused nasal processes. The epithelial plates which separate the nasal fossee from the primitive mouth cavity become thin membra- Nasal septum Ext. naris: Ext. naris Lat. nasal. Lat. nasal process process Ate Med. nasal + process Maxillary process i Mandible Oral cavity Maxillary process Mandible’ : A Med. nasal process Oral cavity Fic. 370.—Two stages in the development of the jaws and nose. A, Ventral view of the end of the head of a 10.5 mm. human embryo (after Peter); B, of an 11.3 mm. embryo (after Rabl). nous structures caudally, and, rupturing, produce two internal nasal openings, the primitive choane (Fig. 153). Cranially, the epithelial plate is destroyed by in- growing mesoderm of the maxillary process and median nasal process which replaces it, thereby forming the primitive palate (Fig. 369 D). The primitive palate forms the ip and the premaxillary palate. The nasal fosse now open ex- ternally through the external nares and internally into the roof of the mouth cavity through the primitive choane. Coincident with these changes the median frontal process has become rela- tively smaller and that portion of it between the external nares and the nasal fossee becomes the nasal septum (Fig. 370). As the facial region grows and elon- 374 THE PERIPHERAL NERVOUS SYSTEM gates, the primitive choanze become longer and form slit-like openings in the roof of the mouth cavity. By the development and fusion of the palatine proc- esses (described on p. 147) the dorsal portion of the mouth cavity is separated off and constitutes the nasal passages (cf. Figs. 371 and 372). The nasal pass- ages of the two sides for a time communicate through the space between the hard palate and the nasal septum. Later, the ventral border of the septum fuses with the hard palate and completely separates the nasal passages (Fig. 372). The nasal passages of the adult thus consist of the primitive nasal fossz plus a portion Olfactory epithelium Corie wf ail es Vomero-nasal organ Cartilage of vomero- i nasal organ. Naso-larcimal duct Dental lamina Fic. 371—Transverse section through the nasal passages and palatine processes of a 20 mm. human embryo. In the nasal septum is seen a section of the vomero-nasal organ (of Jacobson). X 30. of the primitive mouth cavity which has been appropriated secondarily by the development of the hard palate. The passages of the adult thus open caudally by secondary choane into the cavity of the pharynx. Part of the epithelium which lines the nasal fossz is transformed into the sensory olfactory epithelium (Fig. 371). The remainder covers the conche and lines the vomero-nasal organ (of Jacobson), the ethmoidal cells, and the cranial sinuses. The Vomero-nasal Organ (of Jacobson) is a rudimentary epithelial structure which first appears in 8.5 to 9 mm. embryos on the median wall of the nasal fossa DEVELOPMENT OF THE SENSE ORGANS 375 (Fig. 369 C, Z). The groove deepens and closes caudally to form a tubular struc- ture in the cranial portion of the nasal septum (Fig. 371). During the sixth month it attains alength of 4mm. Nerve fibers, arising from cells in its epithelium, join ; en Olfactory epithelium Pe ee ~— Ethmo-turbinal I Cpseahlte Seni nee @ { Kelton ae Hut! Fic. 372.—Transverse section through the nasal passages of a 65 mm. human fetus. xX 14. the olfactory nerve, and it also receives fibers from the . terminalis. In late fetal stages it often degenerates, but may persist in the adult (Merkel, Mangakis). Soft palate Fic. 373.—Right nasal passage of a fetus at term (after Killian). J, Maxillo-turbinal; I7-VI, ethmo- turbinals. The slight elevation at the left of J and IJ is the naso-turbinal. ' Special cartilages are developed for its support (Fig. 371). The organ of Jacob- son is not functional in man, but in many animals evidently constitutes a special olfactory organ. 376 THE PERIPHERAI. NERVOUS SYSTEM The Conche are structures which are poorly developed in man. They ap- pear on the lateral and median walls of the primitive nasal fosse. The inferior concha, or maxillo-turbinal, is developed first in human embryos (Figs. 371 and 372). It forms a ridge along the caudal two-thirds of the lateral wall and is marked off by a ventral groove which becomes the inferior nasal meatus (Fig. 373). The zaso-turbinal is very rudimentary and appears as a slight elevation dorsal and cranial to the infertor concha (Fig. 373). Dorsal to the inferior concha arise five ethmo-turbinals, which grow progressively smaller caudally. According to Peter, the ethmo-turbinals arise on the medial wall of the nasal fossa, and, by a process of unequal growth, are transferred to the lateral wall (Fig. 372). Acces- sory conche are also developed (Killian). In adult anatomy, the inferior concha forms from I (Fig. 373), the middle concha from II, and the superior concha from III and IV. In addition to the ridges formed by the conche, there are developed in the grooves between the ethmo-turbinals the ethmoidal cells. After birth the frontal recess (located between J and IJ, Fig. 373) gives rise to the frontal sinus. During the third month the maxil- lary sinus grows out from the inferior recess of the same groove. The most caudal end of the nasal fossa becomes the sphenoidal sinus, which, as it increases in size, invades the sphenoid bone. The cells of the olfactory epithelium become ciliated, but only a small area, representing the primitive epithelial invagination, functions as an olfactory sense organ. The olfactory cells of this area give rise to the fibers which constitute the olfactory nerve (cf. p. 357). IV. THE DEVELOPMENT OF THE EYE The anlage of the human eye appears in embryos of 2.5 mm. as a thickening and evagination of the neural plate of the fore-brain. At this stage the neural groove of the fore-brain has not closed (Figs. 324, 330 and 382). At 4 mm. the optic vesicles are larger, but still may be connected by a wide opening with the brain cavity (Fig. 374 A, B). In the section shown in Fig. 374 C, the optic vesicle is attached to the ventral brain wall by a distinct optic stalk (cf. Fig. 343). The thickening, flattening, and invagination of the distal and ventral wall of the optic vesicle gives rise to the optic cup (Fig. 374 B-D). The area of invagina- tion also extends ventrally along the optic stalk and produces a groove known as the chorioid fissure (Figs. 331, 375 and 377). At the same time that the optic vesicle is converted into the optic cup, the ectoderm overlying the former thickens, as seen in Fig. 374 B, forming the lens plate, or optic placode. This plate invaginates to form the lens pit, the external opening of which closes in embryos of 6 to 7 mm. (Fig. 374 D), producing the lens vesicle, which remains at first attached to the overlying ectoderm. In an DEVELOPMENT OF THE SENSE ORGANS 377 embryo of 10 mm. (Fig. 376) the lens vesicle has separated from the ectoderm, which will form the epithelium of the cornea. The lens vesicle in earlier stages Anlage of lens Optic vesicle Retinal layer Fic. 374.—Stages in the early development of the humaneye. A, B, at 4mm. (X 27); C, at 5mm. (X 23); D, at 6.25 mm. (X 18) (after Keibel and Elze). (Fig. 374 D) is closely applied to the inner wall of the optic cup, but now it has separated from it, leaving a space in which the vitreous body is developing. The inner retinal layer of the optic cup has become very thick and is applied to the outer layer, so that the cavity of the primi- tive optic vesicle is nearly ob- literated (Fig. 376). Pigment granules have begun to appear in the outer cells which form the pigment layer of the retina. Mes- enchymal tissue surrounds the optic cup and is beginning to make its way between the lens vesicle and the ectoderm. Here Crystalline lens Chorioid fissure Fic. 375.—The optic stalk, cup and lens of a human embryo of 12.5 mm. The chorioid fissure has not yet ex- tended along the optic stalk (from Fuchs, after Hoch- stetter). xX 90. the anterior chamber of the eye develops later as a cleft in the mesoderm. The distal mesenchymal tissue (next the ectoderm) forms the substantia propria of the THE PERIPHERAL NERVOUS SYSTEM Optic recess of brain 378 Vitreous body Optic stalk Mesenchyma Lens vesicle SHY tan Psi. 2 Se foam 2n28h 722 isso a s $ Oe 28 / 5 \ ' 3 Epithelium of cornea Pigment layer of retina Nervous layer of retina Frc. 376.—A transverse section through the optic cup, stalk and lens of a 10 mm. human embryo. x 100. ; Epithelial layer of lens Pigment layer of the retina Central artery SN = ss on Mr & wel tas Serih Pre Be an Vitreous body Bio. ef BN ( ; Layer of lens fibers Mesenchyme Fic. 377.—Transverse section passing through the optic cup at the level of the chorioid fissure. The central artery of the retina is seen entering the fissure and sending a branch to the proximal surface of the lens; from a 12.5 mm. humanembryo. X 105. cornea and its posterior epithelium, while the proximal mesenchyma (next the lens) differentiates into the vascular capsule of the lens. The mesenchyme sur- rounding the optic cup is continuous with that which forms the cornea and later DEVELOPMENT OF THE SENSE ORGANS 379 gives rise to the sclerotic layer, to the chorioid layer, and to the anterior layers of the ciliary body and iris. Both the inner and outer layers of the optic cup are continued into the optic stalk, as seen in Fig. 376. This is due to the trough-like invagination of the ventral wall of the optic stalk} the chorioid fissure, when the optic vesicle is trans- formed into the optic cup (Fig. 375). Into the chorioid fissure grows the central artery of the retina, carrying with it into the posterior cavity of the eye a small amount of mesenchyme (Fig. 377). Branches from this vessel extend to the posterior surface of the lens and supply it with nutriment for its growth. Ata later stage the chorioid fissure Epithelial layer closes, so that the distal rim of = the optic cup forms a complete circle. If the chorioid fissure fails to close, the optic cup remains open at one point and this results in the de- Capsule fective development of the iris, ciliary body, and chorioid layer. Such a Vascular defect is known as coloboma. S membrane The old view that the develop- ment of the lens vesicle causes the Lens fibers formation of the optic cup by push- ing in its distal wall has been dis- proved by W. H. Lewis, for if an anlage of the optic vesicle from an amphibian embryo be transplanted to some other part of the embryo, it can develop into an optic cup in the absence of a lens. Furthermore, it is the contact of optic vesicle with ectoderm that furnishes the stimulus for lens formation, both normally and after trans- plantation to foreign regions, e. g., abdomen. Ectoderm Fic. 378.—Section through the lens and corneal ecto- derm of a16 mm. pigembryo. X 140. The lens vesicle, and its early development from the ectoderm, have been de- scribed. Its proximal wall is much thickened in 10 mm. embryos, and these cells form the Jens fibers (Fig. 376) which will soon obliterate the cavity of the vesicle, as in embryos of 15 to 17 mm. (Fig. 378). The cells of the distal layer remain of a low columnar type and constitute the epithelial layer of the lens. When the lens fibers attain a length of 0.18 mm. they cease forming new fibers by cell division. New fibers thereafter arise from the cells of the epithelial layer at its line of union with the lens fibers. The nuclei are arranged in a layer convex toward the outer surface of the eye and later degenerate, the degeneration begin- 380 THE PERIPHERAL NERVOUS SYSTEM ning centrally. Lens sutures are formed on the proximal and distal faces of the lens when the longer newly formed peripheral fibers overlap the ends of the shorter central fibers. By an intricate but orderly arrangement of fibers these sutures are later transformed into lens-stars of three, and finally of six or nine rays (Fig. 379). The structureless capsule of the lens is probably derived from the lens cells. The lens, at first somewhat triangular in cross section, becomes nearly spherical at three months (Fig. 379). Raphe between Posterior epithelium palpebra of cornea Anterior epiihelium of corned Anterior chamber Cornea Epithelium of lens Pars iridica retn@ Pigment layer of retina Pars optica reting Lens fibers Lens capsule Vitreous : a body & te : = é FAM Xervarne Hin: Fic. 379.—Section through the distal half of the eyeball and through the eyelids of a 65 mm. human fetus. X 35. The origin of the vitreous body has been in doubt, one view deriving it from the mesenchyma which enters the optic cup through the chorioid fissure and about the edge of lens, another view holding that it arises from cytoplasmic processes of cells in the retinal layer. It is certain that the vitreous tissue is formed before mesenchyma is present in the cavity of the optic cup. Szily (Anat. Hefte, Bd. 35, 1908) regards this primitive vitreous body as a DEVELOPMENT OF THE SENSE ORGANS 381 derivative of both retinal and lens cells, it forming a non-cellular network of cytoplasmic processes which are continuous with the cells of the lens and retina. With the ingrowth of the central artery of the retina, from which the artery of the lens passes to the proximal sur- face of the lens and branches on it, a certain amount of mesenchymal tissue invades the optic cup, and this tissue probably contributes to the development of the vitreous body (Tig. 377). The vitreous body may therefore be regarded as a derivative both of the ectoderm and of the mesoderm. The mesenchyma accompanying the vessels to the proximal surface of the lens, and that on its distal surface, give rise to the vascular capsule of the lens (Fig. 377). On the distal surface of the lens this is supplied by branches of the anterior ciliary arteries and is known as the pupillary membrane; the vessels disappear and the membrane degenerates just before birth. The artery of the <—External limiting A ‘i & DCEO Ae Ate ee membrane Cone a | , A ieee me nes ee Ree JO a “= TLayer of rod and cone cells Fiber of Miiller Amacrine cell Internal limiting membrane Frc. 380.—Section of the nervous layer of the retina from a 65 mm. human fetus. At the left is shown diagrammatically the cellular elements of the retina according to Cajal. 440. lens also degenerates, its wall persisting as the transparent hyaloid canal. Fibrille extending in the vitreous humor from the pars ciliata of the retinal layer to the cap- sule of the lens persist as the zonula ciliaris or suspensory ligament of the lens. Differentiation of the Optic Cup.—We have seen that of the two layers of the optic cup the outer becomes the pigment layer of the retina. Pigment granules appear in its cells in embryos of 7 mm. and the pigmentation of this layer is marked in 12 mm. embryos (Fig. 377). The inner, thicker layer of the optic cup, the retinal layer, is subdivided into a distal zone, the pars ceca, which is non-nervous, and into the pars optica, or the nervous retina proper. The line of demarcation between the pars optica and the pars caca is a serrated circle, the ora serrata. The blind portion of the retinal layer, the pars czeca, with the development of the ciliary bodies is differentiated 382 THE PERIPHERAL NERVOUS SYSTEM into a pars ciliaris and pars iridis retine. The former, with a corresponding zone of the pigment layer, covers the ciliary bodies. The pars iridis forms the proxi- mal layer of the iris and blends intimately with the pigment layer in this region, its cells also becoming heavily pigmented (Fig. 379). The pars optica, or nervous portion of the retina, begins to differentiate proximally, the differentiation extending distally. An outer cellular layer and an inner fibrous layer may be distinguished in 12 mm. embryos (Fig. 377). These correspond to the cellular Pigment layer layer (ependymal and mantle Rods and Cones . zones) and marginal layer of ar eee ae the neural tube. In fetuses Outer reticular. layer of 65 mm. (C R) the retina ror WD shows three layers, large Be ees ime nuclear layer ganglion cells having ‘tai dé grated in from the outer cellular layer of rods and cones (Fig. 380). In a fetus of the seventh month all the layers of the adult retina cele He Tet may be recognized (Fig. 381). Fibers of Miiller As in the wall of the neural tube, there are differentiated aN oTharine Walt in the retina supporting tis- ll Fic. 381.—Section through the pars optica of the retina from a seven months’ fetus. X 440. Internal limiting membrane ’ ‘ = une . sue and nervous tissue. The supporting elements, or fibers of Miiller, resemble epen- dymal cells and are radially arranged (Figs. 380 and 381). Their terminations form internal and external limiting membranes. The neuroblasts of the retina differentiate into an outer layer of rod and cone cells, the visual cells of the retina, which are at first unipolar (Fig. 381). Internal to this layer are layers of bipolar and multipolar cells. The inner layer of multipolar cells constitutes the ganglion cell layer. Axons from these cells form the inner nerve fiber layer of optic fibers. These converge to the optic stalk, and, in embryos of 15 mm., grow back in its wall to the brain. The cells of the optic stalk are converted into neuroglia supporting tissue and the cavity of the stalk is gradually obliterated. The optic stalk is thus transformed into the optic nerve (cf. p. 358). DEVELOPMENT OF THE SENSE ORGANS 383 The Sclerotic and Chorioid Layers, and their Derivatives.—After the mes- enchyme grows in between the ectoderm and the lens (Fig. 377), the lens and op- tic cup are surrounded by a condensed layer of mesenchymal tissue, which gives rise to the supporting and vascular layers of the eyeball. By condensation and differentiation of its outer layers, a dense layer of white fibrous tissue is developed, which forms the sclerotic layer. This corresponds to the dura mater of the brain. In the mesenchyme of 25 mm. embryos a cavity appears distally which separates the condensed layer of mesenchyme continuous with the sclerotic from the vascu- lar capsule of the lens (Fig. 379). This cavity is the anterior chamber of the eye and separates the anlage of the cornea from the lens capsule. An inner layer of mesenchyme, between the anlage of the sclerotic and the pigment layer of the retina, becomes highly vascular during the sixth month. Its cells become stellate in form and pigmented, so that the tissue is loose and reticulate. This vascular tissue constitutes the chorioid layer, in which course the chief vessels of the eye. The chorioid layer corresponds fo the pia mater of the brain. Distal to the ora serrata of the retinal layer the chorioid is differen- tiated: (1) into the vascular folds of the ciliary bodies; (2) into the smooth fibers of the ciliary muscle; (3) into the stroma of the iris. The proximal pigmented layers of the iris are derived from the pars iridis retina and from a corresponding zone of the pigment layer. Of these, the pigment layer cells give rise to the sphincter and dilator muscles of the iris. These smooth muscle fibers are thus of ectodermal origin. The Eyelids appear as folds of the integument in 20 mm. embryos. The lids come together and the epidermis at their edges is fused in 33 mm. embryos (Fig. 379). Later, when the epidermal cells are cornified, separation of the eyelids takes place. A third rudimentary eyelid, corresponding to the functional nicti- tating membrane of lower vertebrates, forms the plica semilunaris. The epi- dermis of the eyelids forms a continuous layer on their inner surfaces known as the conjunctiva, which in turn is continuous with the anterior epithelium of the cornea. The Eyelashes, or cilia, develop like ordinary hairs and are provided with small sebaceous glands. In the tarsus, or dense connective tissue layer of the eyelids, which lies close to the conjunctival epithelium, there are developed about 30 tarsal (Meibomian) glands. These arise as ingrowths of the epithelium at the edges of the eyelids, while the latter are still fused. The Lacrimal Glands appear in embryos of about 25 mm., according to Keibel and Elze. They arise as five or six ingrowths of the conjunctiva, dorsally 384 THE PERIPHERAL NERVOUS SYSTEM and near the external angle of the eye. The anlages are at first knob-like, but rapidly lengthen into solid epithelial cords. They begin to branch in 30 mm. embryos. At stages between 50 and 60 mm. (C R) additional anlages appear which also branch. In 38 mm. (C R) embryos a septum begins to partition the gland into orbital and pal- pebral portions. ‘This septum is complete at 60 mm. (C R), the five or six anlages first de- veloped constituting the peripheral orbital part. Lumina appear in the glandular cords in fetuses of 50 mm. (C R) by the degeneration of the central cells. ‘Accessory lacrimal glands appear in 300 mm. (C R) fetuses. The lacrimal gland is not fully differentiated at birth, being only one-third the size of the adult gland. In old age marked degeneration occurs. The Naso-lacrimal Duct arises in 12 mm. embryos as a ridge-like thickening of the epithelial lining of the naso-lacrimal groove (Fig. 149), which, it will be remembered, extends from the inner angle of the eye to the olfactory fossa. This thickening becomes cut off, and, as a solid cord, sinks into the underlying meso- derm (Schaeffer). Secondary sprouts growing out from this cord to the eyelids form the lacrimal canals. A lumen, completed at birth, appears during the third month (Fig. 372). V. THE DEVELOPMENT OF THE EAR The human ear consists of a sound-conducting apparatus and of a receptive organ. The conveyance of sound is the function of the external and middle ears. Hind-brain Auditory ganglion Auditory placode ’ : ; a Otic vesicle Optic vesicle A B Fic. 382.—Two stages in the early development of the internal ear (after Keibel and Elze). A, Horizontal section through the head and open neural tube of a 2 mm. human embryo showing the auditory placode and ganglion (X 27); B, section through the hind-brain and otic vesicles of a 4mm. human embryo (X 33). The end organ proper is the inner ear with the auditory apparatus residing in the cochlear duct. Besides this acoustic function the labyrinthine portion of the inner ear acts as an organ of equilibration. DEVELOPMENT OF THE SENSE ORGANS 385 The Inner Ear.—The epithelium of the internal ear is derived from the ecto- derm. Its first anlage appears in embryos of 2 mm. as a thickened ectodermal Ectoderm Wall of hind-brain — Neur. 4 Fic. 383.—Four sections through the right otic vesicle of a 4mm. human embryo (after Keibel and Elze). X about 30. r.e., Endolymphatic recess, the anlage of the endolymph duct and sac; 0.v., otic vesicle; Neur. 4, Neur. 5, neuromeres four and five of the myelencephalon. plate, the auditory placode (Fig. 382 A). These are developed, dorsal to the second branchial grooves, at the sides of the hind-brain opposite the fifth neuro- meres (Fig. 383). The placodes are invaginated to form hollow vesicles which close in embryos of 2.5 to 3 mm., but remain temporarily attached to the ectoderm — qoy of myclencephalon (Fig. 382 B). The auditory vesicle, or Endolymph duct otocyst, when closed and de- tached, is nearly spherical, Vesiibsilor anlage but approximately at the point where it was attached to the ectoderm a recess, the ductus endolymphaticus, is Cag earnrnaee formed. The point of origin of this recess is shifted later from a dorsal to a mesial Fic. 384.—Right half of a transverse section through position (Figs. 384 and 3854). the hind-brain and otic vesicle, showing the position of the The en dolymph duck coves: a duct. From a human embryo 6.9 mm. long ponds to that of selachian fishes, which remains permanently open to the exterior. In man, its extremity is closed and dilated to form the endolymphatic sac (Fig. 385 e). The differentiation of the auditory vesicle has been described by His, Jr., and more recently by Streeter (Amer. Jour. Anat., vol. 6, 1906). In an em- bryo of about 7 mm. the vesicle has elongated, its narrower ventral process con- 25 386 THE PERIPHERAI, NERVOUS SYSTEM stituting the anlage of the cochlear duct (Fig. 385 a). The wider, dorsal portion of the otocyst is the vestibular anlage, which shows indications dorsally of the de- veloping semicircular canals. These are formed in 11 mm. embryos as two pouches—the anterior and posterior canals from a single pouch at the dorsal border of the otocyst, the lateral canal later from a lateral outpocketing (Fig. 385 c). Centrally the walls of these pouches flatten and fuse to form epithelial plates. In the three plates thus produced canals are left peripherally, communi- cating with the cavity of the vestibule. Soon the epithelial plates are resorbed, leaving the semicircular canals as in Fig. 385 d, e. Dorsally a notch separates the anterior and posterior canals. Of these canals, the anterior is completed be- fore the posterior. The lateral canal is the last to develop. In a 20 mm. embryo (Fig. 385 e) the three canals are present and the coch- lear duct has begun to coil like a snail shell. It will be seen that the anterior and posterior canals have a common opening dorsally into the vestibule, while their opposite ends and the cranial end of the lateral canal are dilated to form ampulle. In each ampulla is located an end organ, the crista ampullaris, which will be re- ferred to later. By a constriction of its wall the vestibule is differentiated into a dorsal portion, the utriculus, to which are attached the semicircular canals, and a ventral portion, the sacculus, which is connected with the cochlear duct (Fig. 385 e, f). At 30 mm. the adult condition is nearly attained. The sacculus and utriculus are more completely separated, the canals are relatively longer, their ampullz more prominent, and the cochlear duct is coiled about two and a half turns (Fig. 385 f). In the adult, the sacculus and utriculus become completely separated from each other, but each remains attached to the endolymph duct by a slender canal which represents the prolongation of their respective walls. Similarly, the cochlear duct is constricted from the sacculus, the basal end of the former becomes a blind process, and a canal, the ductus reuniens, alone connects the two. The epithelium of the labyrinth at first is composed of a single layer of low columnar cells. At an early stage, fibers fyom the acoustic nerve grow between the epithelial cells in certain regions and these become modified to produce special sense organs. These end organs are the criste ampullares in the ampulle of the semicircular canals, the macule acustice in the utriculus and sacculus, and the spiral organ (of Corti) in the cochlear duct. The criste and macule are static organs, or sense organs for maintaining equilibrium. In each ampulla, transverse to the long axis of the canal, the epi- thelium and underlying tissue form a curved ridge, the crista. The cells of the lat.groove Genet absorpt. veel endolymph. vestib. p. vestib, é - lat. groove pouch “7 £0Ch, pouch cochlea &.6.6mm lateral. b omm.lareral, @. 20mm iateral. . f. 30mm. lateral. Fic. 385.—Six stages in the development of the internal ear (Streeter). X25. The figures show lateral views of models of the left membranous labyrinth—e at 6.6 mm.; 6 at 9mm.; cat 11 mm.; d at 13 mm.; e at 20 mm., and f at 30 mm. The colors yellow and red are used to indicate respectively the cochlear and vestibular divisions of the acoustic nerve and its ganglia. absorp. focus, Area of wall where absorption is complete; crus, crus commune; c. sc. /at., ductus semicircularis lateralis; c. sc. post., ductus semicircularis posterior; v. sc. svp., ductus semicircularis superior or anterior; cochlea, ductus cochlearis; coch. pouch, cochlear anlage; endolymph., appendix endolymphaticus; sacc., sacculus; sac. en- dol., saccus endolymphaticus; simus ut. dat., sinus utriculi lateralis; wéric., utriculus. DEVELOPMENT OF THE SENSE ORGANS 387 epithelium are differentiated: (1) into sense cells with bristle-like hairs at their ends, and (2) into supporting cells. About the bases of the sensory cells nerve fibers from the vestibular division of the acoustic nerve branch. The macule resemble the criste in their development save that larger areas of the epithelium are differentiated into cushion-like end organs. Over the maculz concretions of lime salts may form otoconia which remain attached to the sensory bristles. The true organ of hearing, the spiral organ, is developed in the basal epithe- lium of the cochlear duct, basal having reference here to the base of the cochlea. The development of the spiral organ has been studied carefully only in the lower mammals. According to Prentiss (Amer. Jour. Anat., vol. 14, 1913) in pig em- bryos of 5 cm. the basal epithelium is thickened, the cells becoming highly colum- nar and the nuclei forming several layers. In later stages, 7 to 9 cm., inner and outer epithelial thickenings are differentiated, the boundary line between them being the future spiral tunnel (Fig. 386 A). At the free ends of the cells of the epithelial swellings there is formed a cuticular structure, the membrana tectoria, which appears first in embryos of 4to5 cm. The cells of the inner (axial) thick- ening give rise to the epithelium of the spiral limbus, to the cells lining the internal spiral sulcus, and to the supporting cells and inner hair cells of the spiral organ (Fig. 386 B,C). The outer epithelial thickening forms the pillars of Corti, the outer hair cells, and supporting cells of the spiral organ. Differentiation begins in the basal turn of the cochlea and proceeds toward the apex. The internal spiral sulcus is formed by the degeneration and metamorphosis of the cells of the inner epithelial thickening which lie between the labium vestibulare and the spiral organ (Fig. 386 B,C). These cells become cuboidal, or flat, and line the spiral sulcus, while the membrana tectoria loses its attachment with them. The mem- brana tectoria becomes thickest over the spiral organ and in full term fetuses is still attached to its outer cells (Fig. 386 C). Hardesty (Amer. Jour. Anat., vol. 18, 1915), on the contrary, asserts that the membrana tectoria is not attached permanently to the cells of the spinal organ. From what is known of the development of the spiral organ in human embryos, it follows the same lines of development as described for the pig. It must develop relatively late, how- ever, for in the cochlear duct of a newborn child figured by Krause the spiral sulcus and the spiral tunnel are not yet present. The mesenchyme surrounding the labyrinth is differentiated into a fibrous membrane directly surrounding the epithelium, and into the perichondrium of the cartilage which develops about the whole internal ear. Between these two is a more open mucous tissue which largely disappears, leaving the perilymph 388 THE PERIPHERAL NERVOUS SYSTEM oo io s.c.tymp. B st... ~%, Ay { Na cm tect. Ze \" \ AN A BANOS \ RENO SON i.pil. Fic. 386.—Three stages in the differentiation of the basal epithelium of the cochlear duct to form the spiral organ (of Corti), internal spiral sulcus and labium vestibulare. ., Section through the coch- lear duct of an 8.5 cm. pig fetus (x 120); B, the same from a 20 cm. fetus (X 140); C, from a 30 cm. fetus (near term) (X 140). ep.s.sp., Epithelium of spiral sulcus; /.c., hair cells; 7.ep.c., inner epithelial thickening; i./.c., inner hair cells; 7.p7/., inner pillar of Corti; /ab. vest., labium vestibulare; Limb. sp., limbus spiralis; m. bas., basilar membrane; m. ¢ec!., membrana tectoria; m. vest., vestibular membrane; n. coch., cochlear division of acoustic nerve; 0.ep.c., outer epithelial thickening; 0./.c., outer hair cells; s.sp., sulcus spiralis; sc.tymp., scala tympani; st. H., stripe of Hensen; t.s., spiral tunnel. DEVELOPMENT OF THE SENSE ORGANS 389 space. The membranous labyrinth is thus suspended in the fluid of.the peri- lymph space. The bony labyrinth is produced by the conversion of the cartilage capsule into bone. In the case of the cochlea, large perilymph spaces form above and below the cochlear duct. The duct becomes triangular in section as its lateral wall remains attached to the bony labyrinth, while its inner angle is ad- herent to the modiolus. The upper perilymph space is formed first and is the scala vestibuli, the lower space is the scala tympani. The thin wall separating the cavity of the cochlear duct from that of the scala vestibuli is the vestibular membrane (of Reissner). Beneath the basal epithelium of the cochlear duct a fibrous structure, the basilar membrane, is differentiated by the mesenchyme. The modiolus is not preformed as cartilage, but is developed directly from the mesenchyme as a membrane bone. The development of the acoustic nerve has been described on page 358 with the other cerebral nerves. The Middle Ear—The middle ear cavity is differentiated from the first pharyngeal pouch which appears in embryos of 3mm. The pouch enlarges rap- idly up to the seventh week, is flattened : horizontally, and is in contact with the = mae ° * Br. arch. I ectoderm (Fig. 168). During the latter (Meckel’s cartilage) part of the second month, in embryos of 24 mm., the wall of the tympanic : cavity is constricted to form the auditory - Tngamin| - (Eustachian) tube. This canal lengthens ae. ae i eal and its lumen becomes slit-like during ie Cer tee opine Jas Baal the fourth month. The tympanic cavity arch origin of the auditory ossicles. is surrounded by loose areolar connec- tive tissue in which the auditory ossicles are developed and for a time are em- bedded. Even in the adult, the ossicles, muscles, and chorda tympani nerve retain a covering of mucous epithelium continuous with that lining the tympanic cavity. The pneumatic cells are formed at the close of fetal life. . The development of the auditory ossicles has been described by Broman (Anat. Hefte, Bd. 11, 1899), with whose general conclusions most recent workers agree. The condensed mesenchyma of the first and second branchial arches gives rise to the ear ossicles. The malleus and incus are differentiated from the dorsal end of the first arch (Fig. 387). The cartilaginous anlage of the malleus is continuous ventrally with Meckel’s cartilage of the mandible. Between the malleus and incus is an inter- mediate disk of tissue, which later forms an articulation. When the malleus be- 390 THE PERIPHERAL NERVOUS SYSTEM gins to ossify it separates from Meckel’s cartilage. The incus is early connected with the anlage of the stapes, and the connected portion becomes the crus longum. Between this and the stapes an articulation develops. The stapes and Reichert’s cartilage are derived from the second branchial arch (Fig. 387). The mesenchymal anlage of the stapes is perforated by the stapedial artery, and its cartilaginous anlage is ring-shaped. This form persists until the middle of the third month, when it assumes its adult structure and the stapedial artery disappears. Fic. 388.—Stages in the development of the auricle. (Adapted in part after His). A,11mm.; B, 13.6 mm.; C,15 mm.; D,adult. 1, 2, 3, elevations on the mandibular arch; 4, 5, 6, elevations on the hyoid arch; af, auricular fold; ov, otic vesicle; 1, tragus; 2, 3, helix; 4, 5, antihelix; 6, antitragus. The muscle of the malleus, the fensor tympani, is derived from the first branchial arch; the stapedial muscle from the second arch. The further fact that these muscles are innervated ' by the trigeminal and facial nerves, which are the nerves of the first and second arches re- spectively, points toward a similar origin for the ear ossicles. Fuchs, studying rabbit embryos, on the contrary, concludes: (1) the stapes is derived from the capsule of the labyrinth; (2) the malleus and incus arise independently of the first branchial arch. The External Ear.—The external ear is developed from and about the first ectodermal branchial groove. The auricle arises from six elevations which appear, three on the mandibular, and three on the hyoid arch (Fig. 388). Modern ac- DEVELOPMENT OF THE SENSE ORGANS 391 counts of the transformation of these hillocks into the adult auricle agree in the main. Caudal to the hyoid anlages a fold of the hyoid integument is formed, the auricular fold or hyoid helix. A similar fold forms later, dorsal to the first branch- ial groove, and unites with the auricular fold to form with it the free margin of the auricle. The point of fusion of these two folds marks the position of the satyr tubercle, according to Schwalbe. Darwin’s tubercle appears at about the middle of the margin of the free auricular fold, and corresponds to the apex of the auricle in lower mammals. The éragus is derived from mandibular hillock 1; the helix from mandibular hillocks 2 and 3; the antihelix from hyoid hillocks 4 and 5; the anti- tragus from hyoid hillock 6. The Jobule represents the lower end of the auricular fold. The external auditory meatus is formed as an ingrowth of the first branchial groove. In embryos of 12 to 15 mm. the wall of this groove is in contact dorsally with the entoderm of the first pharyngeal pouch. Later, however, this contact is lost, and during the latter part of the second month, according to Hammar, an ingrowth takes place from the ventral portion of the groove, to form a funnel- shaped canal. The lumen of this tube is temporarily closed during the fourth and fifth months, but later re-opens. During the third month a cellular plate at the extremity of the primary auditory meatus grows in and reaches the outer end of the tympanic cavity. During the seventh month a space is formed by the splitting of this plate, and the secondary inner por- tion of the external meatus is thus developed. The tympanic membrane is formed by a thinning out of the mesodermal tissue in the region where the wall of the external auditory meatus abuts upon the wall of the tympanic cavity. Hence it is covered externally by ectodermal, and inter- nally by entodermal epithelium. INDEX ABDOMINAL pregnancy, 20 Abducens nerve, 116, 361 Accessorius nerve, 116 Acoustic nerve, 92, 116, 358 Acrania, 352 Adipose tissue, 287 Adrenalin, 370 After pains, 241 After-birth, 242 Ale nasi, 145 Alar plate, 323, 332, 335, 337 Allantoic stalk, 66, 97, 120 vessels, 67 Allantois, 57, 66, 69, 74, 83, 93, 97 derivation ‘of, 70, 74 section through, ‘1 Allelomorphs, 21 iveoli of pancreas, 179 Alveolo-lingual gland, 152 Ameloblasts, 156 Amitosis, 12 Amnion, origin of, 65, 73 bat, 74 chick, 55, 62, 65 human, 71, 73 pig, 68 Amniotic fluid, 74 Amphiaster, 13 Amphibia, cleavage of ovum in, 25 gastrulation of, 28 origin of mesoderm in, 30 Amphioxus, cleavage of ovum in, 23 gastrulation of, 28 origin of mesoderm in, 29 Ampulla of ductus deferens, 218 Anal membrane, 160, 205 Anaphase of mitosis, 13 Anchoring villi, 237 Angioblast, 39 chick, 42 human, 243 Animal pole, 23 Anlage defined, 3 Ansa hypoglossi, 355, 360 Antihelix, 391 Antitragus, 391 Anus, 97, 143, 160 Aorta, origin of, 258 chick, 40 descending, 40, 46, 48, 59, 60, 62, 83, 99, 130, 260, 261 dorsal, 46, - 85, 99, 122, 260, 264 pig, 99, 121 ventral, 46, 48, 57, 83, 99, 249, 260 Aortic arches, 59, 60, 121, 122) 263, 264 chick, 57 393 Aortic arches, human, 83, 261 transformation of, 261 Appendicular skeleton, 315 Appendix epididymidis, 218 testis, 218, 219 vermiformis, 172, 174 Aqueduct, cerebral, 330, 337 Archenteron, 28, 29, 31, 34 Archipallium, 346 Arcuate fibers, 335 Area opaca, 36 pellucida, 36 scrotal, 227 vasculosa, 243 Areolar tissue, 286 Artemia, 14 Arteries, axillary, 268 basilar, 264, 266 brachial, 268 carotid, 99, 121, 262, 263, 266 cerebral, 266 choroidal, anterior, 266 ceeliac, 99, 122, 262, 267 development of, 261 epigastric, 266 femoral, 268 gluteal, 268 hepatic, 178 hypogastric, 268 iliac, 123, 267, 268 innominate, 263 intercostal, 266 interosseous, 268 intersegmental, 99, 122, 260, 262, 265 ischiadic, 268 lumbar, 266 mammary, 266 median, 268 mesenteric, 262, 267 inferior, 122 superior, 122, 261 of extremities, 268 of heart, 83 of lower extremity, 268 of pig, 99, 121 of upper extremity, 268 ovarian, 267 peroneal, 268 phrenic, 267 popliteal, 268 pulmonary, 99, 121, 122, 168, 258, 262 radial, 268 renal, 205, 267 sacral, middle, 268 spermatic, 267 spinal, 264 394 INDEX Arteries, stapedial, 390 subclavian, 122, 262, 263, 266, 268 suprarenal, 267 ulnar, 268 umbilical, 86, 99, 123, 135, 260, 267 ventral, 99, 122 ventro-lateral, 99, 122 vertebral, 122, 264 vitelline, 46, 58, 63, 86, 99, 122, 260, 261, 262 chick, 42 Artificial parthenogenesis, 20 Arytenoid cartilage, 166 folds, 117 ridges, 94, 151 swellings, 165 Ascaris megalocephala bivalens, reduction of chromosomes in spermatogenesis of, 16 univalens, 13 Atrial canal, 251 foramina, 98 septa, 251 valves, 259 Atrio-ventricular bundle, 259 foramen, 252 Atrium, 57, 83, 90, 97, 249, 251 Auditory meatus, external, 90, 112, 146, 391 nerve, 358 ossicles, 389 placode, 45, 48, 385 tube, 82, 161, 389 vesicle, 385 Auricle of ear, 146, 390 Auricular fold, 391 Autonomic system, 366 Axial skeleton, 309 Axillary artery, 268 nerve, 356 vein, 276 Axis cylinder of nerve fiber, 302 Azygos vein, 274 Basy, blue, 255 Back, muscles of, 317 Bars, sternal, 311 Bartholin’s glands, 228 Basal plate, 239, 240, 323, 332 Basilar artery, 264, 266 membrane, 389 Basilic vein, 276, 277 Basophiles, 247 Bertin’s renal columns, 202 Bicuspid valves, 121, 259 Bile capillaries, 177 duct, common, 120 Biogenesis, law of, 5 Birds, cleavage of ovum in, 26 gastrulation of, 28 origin of mesoderm in, 31 Bladder, 77, 143, 205, 207 Blastoccele, 24 Blood corpuscles, red, 244, 245 white, 245. See also Leucocytes. elements, monophyletic theory of origin, 243 polyphylectic theory of origin, 243 islands, 38, 42, 243 plates, 247 sinuses, 281 vascular system, pig, 97, 120 vessels, anomalies of, 277 changes at birth, 278 chick, 42, 46, 57 human, 243, 247 pig, 97, 120 primitive, 259 Blue baby, 255 Body cavities, 179 stalk, 71 Bone, cartilage, 288, 289 growth of, 290 cells, 289 destroyers, 289 ethmoid, ossification of, 313 formation, endochondral, 289 perichondral, 289, 290 periosteal, 289 formers, 288 growth of, 290 histogenesis of, 288 lacrimal, 314 lacune, 289 marrow, 289 red, 289 yellow, 290 membrane, 288 of skull, 314 nasal, 314 occipital, ossification of, 312 palate, 314 regeneration of, 291 sphenoid, ossification of, 313 temporal, ossification of, 313 zygomatic, 314 Border vein, 276 Bowman’s capsule, 198, 199 Brachial artery, 268 plexus, 355 vein, 276 Brachium conjunctivum, 337 pontis, 336 Brain, human, 327 of pig, 115 olfactory, 328 vesicles, primary, 322, 327 Branchial arches, 315 chick, 57 human, 82 pig, 89, 94, 112 skeleton, 314 Blastoderm, 26 Blastodermic vesicle, 26 Blastomeres, 23 Blastopore, 29, 31 Blastula, 24 Blood cells, 42, 243, 244 ichthyoid, 244 sauroid, 244 Branchiomerism, 366 Broad ligaments, 221 Bronchi, primary, of pig, 95, 119 ventral, 167 Bronchial buds, 119, 167 Brunner, duodenal glands of, 173 Bulbar limb, 249 swellings, 121 Bulbo-urethral glands, 228 Bulbus cordis, 57, 60, 83, 249 Bundle, atrio-ventricular, 259 ground, 325 median longitudinal, 335 Bursa infracardiaca, 190 omental, 189 inferior recess of, 190 pharyngeal, 162 Cacum, 120, 143, 172, 173, 174 ‘Calcar avis, 351 Calcarine fissure, 351 Calyces of metanephros, 120, 199 Canal, atrial, 251 atrio-ventricular, 252 central, of adult spinal cord, 324 entodermal, 159 Gartner’s, 219 Haversian, 290 hyaloid, 381 incisive (of Stenson), 148 inguinal, 221, 222 lacrimal, 384 pleuro-peritoneal, 183 Stenson’s, 148 Canaliculi, 289 aberrans, 199 Capillaries, bile, 177 Capsule, Bowman’s, 198, 199 cells, 306 internal, 345 of liver, 192 periotic, 312 vascular, of lens, 378, 381 Cardiac diverticulum, 119 glands, 170 muscle, 291, 293 Cardinal veins, 123 anterior, 49, 58, 59, 60, 101, 261, 268, 271 common, 58, 60, 97, 101, 261, 268, 271 posterior, 58, 62, 63, 102, 261, 268, 274 Carotid arteries, 99, 121 common, 263 internal, 262, 263, 266 gland, 369 ‘Carpus, ossification of, 316 Cartilage, arytenoid, 166 bone, 288, 289 growth of, 290 corniculate, 166 cricoid, 166 cuneiform, 166 elastic, 287 fibro-, 287 histogenesis of, 287 * hyaline, 287 Meckel’s, 315 of larynx, 165 Reichert’s, 390 thyreoid, 166, 315 Cauda equina, 326 ‘Caudate lobe of liver, 192 nucleus, 345 Caul, 74, 242 ‘Cavity, body, 179 head, 366 joint, 291 INDEX 395 Cavity, marrow, 290 medullary, 290 oral, 142 pericardial, 53, 179, 180 peritoneal, 53, 185 pleural, 53, 183, 185 pleuro-pericardial, 40 pleuro-peritoneal, 179 tympanic, 161, 389 ae theory of development of nerve fibers, 06 Cells, aggregation, 3 blood, 42, 243, 244 ichthyoid, 244 sauroid, 244 bone, 289 capsule, 306 chromaffin, 368, 369 cone, of retina, 382 decidual, 236 division of, 12 enamel, 156 ependymal, 302, 307, 324 ethmoidal, 313, 376 follicle, 8 ganglion, 305 unipolar, 305 genital, 213 germ, 7, 302 giant, 247 gland, 297 goblet, 283 hair, 295, 296, 387 interstitial, of testis, 213 mass, inner, 71 intermediate, 52 mastoid, 314 migration, 3 multiplication, 3 muscle, smooth, 291 nerve, 300 neuroglia, 300, 302, 307, 308 rod, of retina, 382 sense, 387 sex, 208 sheath (of axis cylinder), 306 sperm, 10 supporting, 371, 387 of neural tube, 307 of spinal ganglia, 305, 306 sustentacular (of Sertoli), 14, 213 taste, 371 Cement of teeth, 157 Centra of vertebre, 142 Central canal of adult spinal cord, 324 nervous system, 321 chick, 44, 55 human, 80, 321 pig, 114 sulcus, 351 Centrosome, 7 Cephalic flexure, 55, 79, 327 pig, 89 vein, 276, 277 Cerebellum, 115, 336 Cerebral aqueduct, 115, 330, 337 artery, anterior, 266 middle, 266 posterior, 266 396 Cerebral cortex, 351 hemispheres, 115, 328, 329, 349 nerves, 115, 357 veins, 273 Cervical duct, 161 enlargement, 326 flexure, 328 pig, 89 ganglion, 368 sixth, 116 sinus, 112 pig, 90- vesicle, 161 Chamber, anterior, of eye, 377, 383 Chick embryos, 36, 43, 55 of fifty hours’ incubation, 55 of twenty hours’ duration, 36 of twenty-five hours’ incubation, 38 preservation of, 36 study of, 36, 43, 55 Chin, 145 Choane, 147 primitive, 373 secondary, 374 Chondrification of skull, 312 of vertebra, 310 Chondrioconta, 285 Chondrocranium, 312 ossification of, 312 Chorda dorsalis, 309 origin of, 35 gubernaculi, 221, 222 tympani, 363 Chordine tendinex, 259 Chorioid fissure of eye, 376, 379 layer of eye, 383 plexus, 141, 142, 334, 338, 342 Chorioidal artery, anterior, 266 fissure, 342, 349 Chorion, origin of, 65 chick, 65 frondosum, 235, 237 human, 72 leve, 235, 237 pig, 68, 70 villi of, 71, 72, 232, 237 Chromaffin bodies, 368 aortic, 369 Chromosomes, 13 accessory, 17, 22 number of, 13 Cilia, 383 Ciliary bodies, 383 ganglion, 361, 368 muscle, 383 Circulation, fetal, 277 portal, 279 vitelline, 46 Circulatory system, 83 Cisterna chyli, 279 Clava, 336 Clavicle, ossification of, 315 Cleavage of ovum, 23 amphibia, 25 Amphioxus, 23 birds, 26 frog, 25, 26 mammals, 26 primates, 27 INDEX Cleavage of ovum, reptiles, 26 Cleft palate, 149 sternum, 316 xiphoid process, 316 Clitoris, 143, 223 Cloaca, 83, 97, 171, 205 anomaly of, 208 Cloacal membrane, 83, 160, 205 tubercle, 225 Closing plates, 57, 60, 95, 118, 160 ring, 239 Coccygeal gland, 282 Cochlear duct, 384, 386 Ceeliac artery, 99, 122, 262, 267 axis, primitive, 267 Ceelom, 29, 33, 180 chick, 40, 53 human, 179 pleural, 96 Ccelomic pouches, 29 Colic valve, 174 Collateral eminence, 351 fissure, 351 Colliculus, facial, 364 inferior, 337 seminalis, 221 superior, 337 Coloboma, 379 Colon, 120, 174 Column, gray, 324 Columns, muscle, 293 renal, 202 Commissura mollis, 341 Commissure, anterior, 346, 348 gray, 325 hippocampal, 347 of telencephalon, 346 posterior, of labia majora, 225 white, 325 Compact layer, 236, 240 Concealed testis, 224 Conche, 146, 313, 376 Concrescence, theory of, 31 Cone cells of retina, 382 Conjunctiva, 383 Connective tissue, 285 white fibrous, 285 Copula, 94, 117, 150 Coracoid process, 316 Cord, genital, 210 medullary, 217 nephrogenic, 197, 201 spermatic, 224 spinal, 322 testis, 212, 213 umbilical, human, 70 of pig, 70 Corium, 295 Cornea, substantia propria of, 377 Corneal tissue, 286 Corniculate cartilages, 166 Corona radiata, 9 Coronary appendages, 192 ligament, 192 sinus, 253, 271 sulcus, 225, 251 Corpora quadrigemina, 330, 337 Corpus albicans, 217 callosum, 346, 348 Corpus hemorrhagicum, 217 luteum, 217 spurium, 217 verum, 217 striatum, 329, 341, 345 Corpuscles, blood, red, 244, 245 white, 245. See also Leucocytes. lamellated, 371 renal, 133, 198, 199 splenic, 282 tactile, 371 thymic, 163 Cortex, cerebral, 351 of cerebral hemispheres, 329 of metanephros, 202 primitive, of cerebral hemisphere, 341 Corti’s organ, 359, 386 pillars, 387 Costal processes, 310 Costo-cervical trunk, 266 Cotyledons of human placenta, 240 Cowper’s glands, 228 Crest, ganglion, 304, 353 neural, 304 Cribriform plates, 313 Cricoid cartilage, 166 Crista ampullaris, 386 galli, 313 inguinalis, 221 terminalis, 254 Crura cerebri, 330 Crus longum, 390 Cryptorchism, 214, 224 Cumulus odphorus, 216 Cuneiform cartilages, 166 Cuneus, 336, 351 Cutis plate, 111 Cuvier’s ducts, 58 Cyclopia, 352 Cystic duct, 120, 177 kidney, 205 Cysts, dermoid, 295 Cytoplasm of ovum, 7 Darwin’s tubercle, 391 Decidua basalis (serotina), 232, 236, 237, 239 capsularis (reflexa), 231, 236 vera (parietalis), 232, 235 Decidual cells, 236 membranes, 230, 231 separation of, 241 teeth, periods of eruption, 157 Dendrites, 304 Dental canaliculi, 157 lamina, 153 papilla, 153, 157 pulp, 157 sac, 157 Dentate nucleus, 337 Dentinal fibers of Tomes, 157 Dentine, 157 Derma, 295 Dermatome, 293 Dermoid cysts, 295 Dermo-muscular plates, 51 Dermo-myotome, 285, 293 Descending tract of fifth nerve, 335, 361 Determination of sex, 22 INDEX 307 Diaphragm, 187, 188 anlage of, 61 anomalies of, 194 Diaphragmatic hernia, 194 Diaphysis, 290 Diaster, 13 Diencephalon, 56, 80, 92, 115, 327, 338 Differentiation of embryo, 3 of tissues, 4 Digestive canal, chick, 45, 57 human, 80 pig, 6 mm., 93 glands, human, 81 Dilator muscles of iris, 383 Discs, intercalated, 293 intervertebral, 310 Dissecting instruments, 137 Dissections, lateral, of viscera, 138 median sagittal, 140 pig embryos, 137 ventral, 143 Diverticulum, cardiac, 119 hepatic, 96, 119, 175 Meckel’s, 79, 171 of ileum, 171 of Nuck, 224 of pharyngeal pouches, 95 Ducts, branchial, 161 cervical, 161 cochlear, 384, 386 common bile, 120 Cuvier’s, 58 cystic, 120, 177 Ebner’s, 152 genital, 208, 210, 218 hepatic, 120, 177 mesonephric, 120, 199, 210 milk, 208 Miillerian, 210 naso-lacrimal, 384 pancreatic, 179 papillary, 201 para-urethral, 227 periportal, 177 pronephric (primary excretory), 196, 199 thoracic, 279 thyreoglossal, 164 vitelline, 159 Ductuli efferentes, 199, 218 Ductus arteriosus, 263, 279 choledochus, 120, 177 deferens, 218 endolymphaticus, 385 epididymidis, 218 reuniens, 386 venosus, 101, 124, 270, 279 Duodenal glands (of Brunner), 173 Duodeno-hepatic ligament, 192 Duodenum, 119, 170, 173 Dyads, 16 Far, 384 auricle of, 146 external, 112, 146, 384, 390 inner, 384, 385 internal, 45 middle, 384, 389 Ebner’s ducts and glands, 152 398 INDEX Ectoderm, 3, 28 formation of, 28 Ectodermal derivatives, histogenesis of, 294 Ectoplasm, 285 Efferent ductules of epididymis, 199 Elastic cartilage, 287 tissue, 286 Eleidin, 294 Ellipsoids of spleen, 282 Embryos, chick, 36, 43, 55 of thirty-eight hours’ duration, 43 of twenty hours’ duration, 36 of twenty-five hours’ duration, 38 preservation of, 36 study of, 36 human, 71 crown-rump length, 87 estimated age, 87 of Coste, 78 of Dandy, 76 of Eternod, 77 of His, 2.5 mm., 78 4.2 mm., 79 Normentafel, 84, 85 of Kromer, 76 of Mall, 76 of Peter, 74 of Spee, 74 of Thompson, 76 pig, 6 mm., 89 10 mm., transverse sections, 125 10 to 12 mm., 112 dissection of, 137 transverse sections of 6 mm., 104 whole, for study, 137 Eminence, collateral, 351 Enamel cells, 156 layer, 156 organs, 153 pulp, 155 Encephalon, 80 Endocardial cushions, 98, 121, 131, 251, 252 Endocardium, 131, 249 chick, 41 Endochondral bone formation, 289 Endolymphatic sac, 385 Endoplasm, 285 Endothelium, 54 Enlargement, cervical, 326 lumbar, 326 Entoderm, 3, 28, 29 formation of, 28 Entodermal canal, 159 epithelium, 170 histogenesis of, 283 Eosinophiles, 246 Ependymal cells, 302, 307, 324 layer, 59, 126, 307, 322, 333 zone, 301 Epicardium, 42, 98, 131, 249 Epidermis, 294 anomalies of, 295 Epididymis, 219 efferent ductules of, 199 Epigastric arteries, 266 Epigenesis, 2 Epiglottis, 94, 116, 143, 151, 165 Epiphysis (pineal gland), 141, 290, 310, 330, 339 Epiploic foramen (of Winslow), 134, 190 Epistropheus, 310 Epithalamus, 330 Epithelia, 3 Epithelial bodies, 82, 163 Epithelium, 54 basal, of cochlear duct, 387 entodermal, 170 histogenesis of, 283 olfactory, 128 respiratory, 168 stratified, 294 Epitrichium, 294, 295, 296 Eponychium, 299 Epoéphoron, 199, 219 Erythroblasts, 244, 245 Erythrocytes, 244, 245 Erythroplastids, 245 Esophagus, 81, 94, 95, 119, 143, 169 Ethmoid bone, ossification of, 313 Ethmoidal cells, 313, 376 Ethmo-turbinals, 376 Eustachian tube, 161, 389 valve, 254 Excretory duct, primary, 62, 196, 199 Expression, muscles of, 320 Extra-embryonic mesoderm, 71 Extremities, arteries of, 268 muscles of, 318 veins of, 276 Eye, chick, 43, 45, 47, 59 human, 80, 376 pig, 89 Eyelashes, 383 Eyelids, 383 Fact, development of, 144 Facial colliculus, 364 nerve, 92, 116, 362, 363 é Falciform ligament, 133, 180, 192 False hermaphroditism, 228 Fasciculi proprii, 325 Fasciculus cuneatus, 325 gracilis, 325 Femoral artery, 268 nerve, 356 vein, 277 Femur, ossification of, 316 Fertilization, 19, 20 significance of, 21 Fertilizin, 20 Fetal circulation, 277 membranes, human, 71 pig, 68 Fetus, 87 relation of, to placenta, 241 Fibrils, horn, 299 Fibro-cartilage, 287 Fibula, ossification of, 316 Filament, axial, of spermatozoén, 12 spiral, of spermatozoin, 11 terminal, of spermatozoén, 11 Filiform papilla, 151 Filum terminale, 326 Fingers, supernumerary, 316 Fissure, calcarine, 351 chorioidal, 342, 349, 376, 379 collateral, 351 great longitudinal, 342 Fissure, hippocampal, 346, 349 lateral, 349 of Rolando, 351 parieto-occipital, 351 Sylvian, 349 ventral median, 325 Fixation of pig embryos, 137 Flagellum of spermatozoén, 11 Flexure, cephalic, 55, 79, 327 cervical, 328 pig, 89 iliac, 174 pontine, 327 Flocculus, 337 Floor plate, 322, 324, 332 Foliate papilla, 152 Follicle cells, 8 Follicles, Graafian, 9, 215 primordial, 215 vesicular, 215 Fontanelles, 314 Foramen, atrio-ventricular, 98 cecum, 151, 164 epiploic (of Winslow), 134, 190 interatrial, 98, 253 interventricular, 115, 258, 329, 343 closure of, 259 mandibular, 315 Monro’s, 343 of Winslow, 134, 190 ovale, 98, 120, 253, 254, 255 section through, 130 Fore-brain, chick, 40, 43, 44, 47, 59 human, 327 Fore-gut, chick, 39, 40, 41, 49, 57 human, 81, 159, 160 pig, 93 Fore-skin, 226 ' Fornices of vagina, 220 Fornix, 346, 347 Fossa, incisive, 148 olfactory, 371, 372 ovalis, 255 supratonsillar, 161 tonsillar, 161 Fovea cardiaca, 39, 40, 41, 83 chick, 49 Frenulum prepucii, 226 Frog, cleavage of ovum in, 25, 26 Frontal operculum, 349 sinus, 376 Fronto-nasal process, 372 Fronto-parietal operculum, 349 Froriep’s ganglion, 93, 116, 360 Fundus of uterus, 220 Fungiform papille, 151 Funiculi of spinal cord, 325 Furcula of His, 165 Gatt bladder, 120, 177 Ganglion, 353 accessory, 364 cell layer, 382 of retina, 358 cells, 305 unipolar, 305 cervical, 368 ciliary, 361, 368 INDEX 399 Ganglion crest, 304, 353 Froriep’s, 93, 116, 360 geniculate, 92, 116, 363 habenule, 338 jugular, 93, 116 nodose, 93, 116, 364 otic, 368 petrosal, 93, 116, 364 prevertebral, 368 root, 93, 364 semilunar, 92, 116, 361 sphenopalatine, 368 spinal, 50, 116, 304 supporting cells, 305, 306 spiral, 358, 359 submaxillary, 368 superior, 93, 116, 364 sympathetic, 305, 367 trunk, 364 vestibular, 358 vagus accessory, 116 visceral, 368 Gartner’s canals, 219 Gastric glands, 170 Gastro-hepatic ligament, 192 Gastro-lienic ligament, 191 Gastrula, 28 Gastrulation, 28 of amphibia, 28 of Amphioxus, 28 of birds, 28 of mammals, 29 of reptiles, 28 Geniculate bodies, 330 ganglion, 92, 116, 363 Genital cells, 213 cord, 210 ducts, 208, 210, 218 eminence, 114, 225 fold, 97, 120, 143, 197, 208 glands, 97, 143, 208 and mesonephric tubules, union of, 218 swellings, 225 tubercle, 225 Genitalia, external, 224 internal, ligaments of, 221 Germ cells, 7, 302 layers, 2, 3 derivatives of, 54 origin of, 23 plasm, continuity of, 4 Germinal disc, 26 Giant cells, 247 Gill slits, 55 Glands, accessory genital, 227 alveolo-lingual, 152 Bartholin’s, 228 Brunner’s, 173 bulbo-urethral, 228 cardiac, 170 carotid, 369 cells, 297 coccygeal, 282 Cowper’s, 228 duodenal (of Brunner), 173 Ebner’s, 152 gastric, 170 genital, 97, 143, 208 and mesonephric tubules, union of, 218 400 Glands, hemolymph, 281 intestinal, 173 lacrimal, 383 accessory, 384 lymph, 281 mammary, 114, 297 rudimentary, 298 supernumerary, 298 Meibomian, 383 parathyreoid, 118, 163 parotid, 152 pineal, 141, 290, 310, 330, 339 prostate, 227 salivary, 152 sebaceous, 296 sublingual, 152 submaxillary, 152 sudoriparous, 297 suprarenal, 143, 368, 369 sweat, 297 tarsal, 383 thymus, 118 thyreoid, 118, 164 urogenital, 144 uterine, of pregnancy, 236 vestibular, 228 Glans clitoridis, 225 penis, 226 Glomerulus, 133, 195, 198 Glomus caroticum, 369 coccygeum, 282 Glossopharyngeal nerve, 93, 116, 362, 364 Glottis, 94, 117, 151 Gluteal artery, 268 vein, 277 Goblet cells, 283 Gonads, 83 Graafian follicle, 9, 215 Granular layer of cerebellum, 337 leucocytes, 246 Granules, pigment, 295 Gray column, 324 commissures, 325 rami, 367 Groove, laryngo-tracheal, 164 neural, 300 primitive, 31 rhombic, 334 urethral, 225 Ground bundles, 325 Growth of embryo, 3 Gubernaculum testis, 222, 223 Gyrus dentatus, 346 hippocampi, 346 Hemopottsis, 243 Hair, 295 bulb, 296 cells, 295, 296, 387 papilla, 296 shaft of, 296 sheath, 296 Hare lip, 146 Haversian canal, 290 Head cavities, 366 fold, 39 muscles of, 319 process, 32, 33, 37, 38 INDEX Head, vertebrate, segmentation of, 365 Heart, chick, 41, 46, 49 descent of, 259 human, 83, 247, 248 pig, 90, 97, 116, 120° 143 primitive, chick, 42 ventricle of, 57 Helix, 391 hyoid, 391 Hemiazygos vein, 274 Hemispheres, cerebral, 328, 329, 349 Hemolymph glands, 281 Henle’s loop, 203 Hensen’s knot, 31, 36, 51 Hepatic artery, 178 diverticulum, 96, 119, 175 duct, 120, 177 vein, 270 common, 98 Heredity, Mendel’s law of, 21 Hermaphroditism, 228 false, 228 Hernia, diaphragmatic, 194 inguinal, 224 umbilical, 70 Hind-brain, chick, 41, 44, 48, 59 human, 80, 327 Hind-gut, 57, 64, 83, 93, 159, 160 Hippocampal commissure, 347 fissure, 346, 349 Hippocampus, 346, 349 minor, 351 His, furcula of, 165 Histogenesis, 283 defined, 4 of bone, 288 of cartilage, 287 of ectodermal derivatives, 294 of entodermal epithelium, 283 of mesodermal tissues, 284 of muscle, 291 of nervous tissue, 300 Historical, 1 Horn fibrils, 299 gray, 324 greater, of hyoid bone, 315 lesser, of hyoid bone, 315 Horse-shoe kidney, 205 Howship’s lacune, 289 Human embryos, 71 crown-rump length, 87 estimated age, 87 of Coste, 78 of Dandy, 76 of Eternod, 77 of His, 2.5 mm., 78 4.2 mm., 79 Normentafel, 84, 85 of Krémer, 76 of Mall, 76 of Peter, 74 of Spee, 74 of Thompson, 76 Humerus, ossification of, 316 Hyaline cartilage, 287 Hyaloid canal, 381 Hydramnios, 74 Hymen, 219, 221 Hyoid arch, 90 Hyoid helix, 391 Hyomandibular cleft, 90 Hypogastric artery, 268 Hypoglossal nerve, 93, 116, 151, 360 Hypophysis, 57, 59, 330 anterior lobe of, 50 posterior lobe of, 115 Hypospadias, 227 Hypothalamus, 330 Icutuyorp blood cells of Minot, 244 Tleum, 83 diverticulum of, 171 Tliac arteries, 123, 267, 268 flexure, 174 veins, 274, 275 Tlium, ossification of, 316 Implantation of ovum, 231 Incisive canals (of Stenson), 148 fossa, 148 Incus, 315, 389, 390 Infundibulum, 330, 339 Inguinal canal, 221, 222 fold, 220, 221 hernia, 224 Inner cell mass, 71 epithelial mass of gonad, 208 Innominate artery, 263 Instruments, dissecting, 137 Insula, 349 Interatrial foramen, 98, 252 Intercalated discs, 293 Intercostal arteries, 266 Intermediate cell mass, 40, 52 Interosseous artery, 268 Intersegmental arteries, 99, 122, 260, 262, 265 fiber tracts, 335 veins, 274 Interstitial cells of testis, 213 Interventricular foramen, 115, 258, 329, 343 closure of, 259 septum, 121, 258 sulcus, 258 Intervertebral discs, 310 muscles, 317 Intestinal glands, 173 loop, 143, 170 Intestine, human, 81, 83, 169, 170 pig, 96, 120 villi of, 173 Introduction, 1 Tris, 382, 383 muscles of, 383 Ischiadiac vein, 274 artery, 268 Ischium, ossification of, 316 Island of Reil, 349 Tslands, blood, 243 of pancreas, 179 Isolecithal ova, 23 Isthmus, 115, 328, 330 Jacosson’s organ, 357, 374 Joint cavity, 291 Joints, 291 Jugular ganglion, 93, 116 sacs, 279 veins, 123, 273 26 INDEX 401 KeraTIN, 299 Keratohyalin, 294 Kidney, anomalies of, 205 calyces of, 120 cystic, 205 horse-shoe, 205 human, 199 tubules of, 120, 201, 203 Knot, primitive (of Ilensen), 36, 51 Lanta majora, 225 minora, 225, 227 Labyrinth, membranous, 45 Lacrimal bone, 314 canals, 384 glands, 383 accessory, 384 groove, 90 *Lacune, bone, 289 Howship’s, 289 Lamelle, periosteal, 290 Lamellated corpuscles, 371 Lamina perpendicularis, 313 terminalis, 329, 342, 346 Langhans’ layer, 238 Laryngeal nerves, recurrent, 264 Laryngo-tracheal groove, 164 Larynx, 164, 165 cartilage of, 165 muscles of, 320 ventricles of, 165 Law, Mendel’s, of heredity, 21 of biogenesis, 5 of recapitulation, 5 Layer, chorioid, of eye, 383 compact, 236, 240 enamel, 156 ependymal, 126, 307, 322, 333 epitrichial, 296 ganglion cell, 382 of retina, 358 = germ, origin of, 23 granular, 337 Langhans’, 238 mantle, 126, 322, 324 marginal, 126, 322, 325 medullary, 337 molecular, 337 nerve fiber, 382 nervous, of retina, 126 of retina, 382 pigment, of retina, 126, 377, 381 retinal, 377, 381 sclerotic, of eye, 383 spongy, 236, 240 Lecithin, 7 Lemniscus, 338 median, 335 Lens of eye, chick, 45, 47 human, 376 fibers of, 379 pupillary membrane of, 381 suspensory ligament of, 381 vascular capsule of, 378, 381 pig, 89 pit, 376 plate, 376 vesicles, 59, 376, 379 402 Lens-stars, 380 Lenticular nuclei, 345 Lesser peritoneal sac, 133, 189 Leucocytes, 245 granular, 246 mast, 247 mononuclear, large, 246 non-granular, 245 polymorphonuclear, 246 Ligament, broad, 221 coronary, 192 duodeno-hepatic, 192 falciform, 133, 180, 192 gastro-hepatic, 192 gastro-lienic, 191 lieno-renal, 191 of internal genitalia, 221 of liver, 191 of testis, 221 proper, of ovary, 221 round, 220, 222 spheno-mandibular, 315 stylo-hyoid, 315 suspensory, of lens, 381 Ligamentum arteriosum, 279 labiale, 222 ovarii, 210 scroti, 222 teres, 271, 279 testis, 210, 222 umbilicale medium, 208 venosum, 270, 279 Limbus ovalis, 254 Limiting membranes of retina, 382 Line, milk, 298 Linguo-facial vein, 101 Lip, 373 ; hare, 146 rhombic, 334 Liver, anlage of, 57, 62, 175 anomalies of, 178 caudate lobe of, 192 cords, 131 human, 81, 175 ligaments of, 191 lobules of, 178 pig, 90, 93, 96, 119 quadrate lobe of, 192 sinusoids of, 57, 62, 176 Lobes of cerebrum, 349 Lobule of ear, 391 Lobules of liver, 178 Lobuli epididymidis, 218 Lumbar arteries, 266 enlargement, 326 veins, 276 Lumbo-sacral plexus, 356 Lung buds, 82 Lungs, human, 81, 164, 167 apical buds, 167 changes at birth, 168 stem buds, 167 pig, 95, 119 Lunula, 299 Lymph glands, 281 sacs, 279, 280 Lymphatic system, 279 Lymphatics, origin of, 279 peripheral, 279 INDEX Lymphocytes, small, 245 Lymphoid tissue of spleen, 282 MacuL acustice, 386 Magma reticulare, 71 Mall’s pulmonary ridge, 183 Malleus, 315, 389 muscles of, 390 Mammals, cleavage of ovum in, 26 gastrulation of, 29 origin of mesoderm in, 32 Mammary arteries, 266 glands, 114, 297 rudimentary, 298 supernumerary, 298 Mammillary bodies, 330, 347 recess, 330, 341 Mandibular arch, 90 foramen, 315 nerve, 116, 361 process, 79, 80, 90, 112, 314, 372 Mantle layer, 126, 322, 324 Manubrium, 311 Marginal layer, 126, 322, 325 sinus, 241 zone, 302 Margo thalamicus, 327 Marrow, bone, 289 red, 289 yellow, 290 cavity, 290 Massa intermedia, 341 Mast leucocytes, 247 Mastication, muscles of, 319 Mastoid cells, 314 process, 314 Maturation, 12, 14 of mouse ovum, 18 significance of, 21 Maxille, 315 Maxillary nerve, 116, 361 process, 79, 80, 90, 112, 314, 372 sinus, 376 Maxillo-turbinal anlage, 376 Meatus, external auditory, 90, 112, 146, 391 inferior nasal, 376 Meckel’s cartilage, 315 diverticulum, 79, 171 Meconium, 175 Median artery, 268 longitudinal bundle, 335 nerve, 356 Mediastinum, 167 of ovary, 214 testis, 213 : Medulla oblongata, 80, 33 Medullary cavity, 290 cords, 217 layer, 337 sheath, 306 velum, 330, 337 Megakaryocytes, 247 Meibomian glands, 383 Membrana tectoria, 387 Membrane, anal, 160, 205 basilar, 389 bone, 288 bones of skull, 314 INDEX Membrane, cloacal, 160, 205 decidual, 230, 231 separation of, at birth, 241 tympanic, 117 limiting, of retina, 382 obturator, 316 pericardial, 187 Pharyngeal, 159 pleuro-pericardial, 182, 183 pleuro-peritoneal, 182, 183 pupillary, 381 Reissner’s, 389 synovial, 291 tympanic, 391 urogenital, 160, 205 vestibular, 389 vitelline, 7 Membranous labyrinth, 45 Mendel’s law of heredity, 21 Menstruation, 10, 230 uterus during, 230 Mesameeboids, 243, 244 Mesencephalon, 80 chick, 44, 48, 60 human, 330, 327, 337 pig, 92, 115 Mesenchyma, 3 chick, 41, 53 human, 384 Mesenteric arteries, 262, 267 inferior, 122 superior, 261 veins, 270 superior, 99, 100, 122, 125 Mesentery, 93, 96, 120, 133, 179, 180, 191, 192 anomalies of, 194 dorsal, 81, 192 Mesocardium, 180 dorsal, 49, 249 Mesocolon, 180, 193, 194 Mesoderm, 3, 28 amphibian, 30 Amphioxus, 29 birds, 31 extra-embryonic, 34, 71 intra-embryonic, 34 mammal, 32 origin of, 29 primary, 28 reptiles, 30 somatic, 52, 53, 69 splanchnic, 53, 69, 169, 366 Tarsius, 34 Mesodermal segments, 2, 40, 51, 62, 64 tissues, histogenesis of, 284 Mesoduodenum, 180, 193 Mesogastrium, 180 Mesonephric duct, 49, 52, 62, 97, 120, 199, 210 fold, 197 tubules, 197 and genital glands, union of, 218 Mesonephros, 52, 83, 90, 93, 97, ‘120, 143, 195, 197 Mesorchium, 210 Mesorectum, 180, 194 Mesothelium, 54, 284 peritoneal, 170 Mesovarium, 210 Metameres, 2 Metamerism, 2 403 Metanephros, 52, 97, 120, 143, 195, 199 and umbilical arteries, section through, 136 calyces of, 199 collecting tubules, 199, 201 cortex, 202 pelvis, 199 tubules, 199, 201 ureter, 199 Metaphase of mitosis, 13 Metatarsus, ossification of, 316 Metathalamus, 330 Metencephalon, 80, 92, 115, 327, 328, 336 Methods of study, 5 Mid-brain, 80, 327 chick, 43, 44, 47 Mid-gut, 57, 159 Migration, cell, 3 Milk ducts, 298 line, 114, 298 teeth, periods of eruption, 157 Minot’s ichthyoid blood cells, 244 Mitosis, 12 phases of, 12-14 significance of, 21 Mitotic figure, 13 Mitral valve, 259 Moderator muscles, 259 Mcediolus, 389 Molecular layer, 337 Monaster, 13 Mononuclear leucocytes, large, 246 eis theory of origin of blood elements, Monro’s foramen, 343 Mons pubis, 233 Montgomery’s rudimentary mammary glands, 298 Morula, 24 Motor nerves, somatic, 360 Mouse ovum, fertilization of, 19 maturation of, 18 Mouth, pig, 6 mm., 93 Miiller’s fibers, 382 tubercle, 221 Miillerian ducts, 210 Multiplication, cell, 3 Muscles, 316 anomalies of, 320 cardiac, 291, 293 ciliary, 383 columns, 293 dilator, of iris, 383 histogenesis of, 291 intervertebral, 317 moderator, 259 of back, 317 of expression, 320 of extremities, 318 of head, 319 of larynx, 320 of malleus, 390 of mastication, 319 of neck, 317 of pharynx, 320 of tongue, 320 of trunk, 317 papillary, 259 plate, 60, 62 skeletal, 291, 292 smooth, 291 404 Muscles, sphincter, of iris, 383 stapedial, 390 sterno-cleido-mastoid, 364 thoraco-abdominal, 317 trapezius, 364 voluntary, 52 Muscular system, 316 Musculocutaneous nerve, 356 Myelencephalon, 80, 92, 115, 328, 330, 332 Myelin, 306 development of, 326 sheath, 306 Myelocytes, 245, 246 Myoblasts, 292, 293 Myocardium, 42, 98, 249, 259 Myofibrille, 293 Myotomes, 2, 292 changes in, during formation of adult muscles, 31 chick, 51 Nait fold, 298, 299 human, 298 Naris, external, 373 Nasal bone, 314 meatus, inferior, 376 passages, 374 processes, 145, 372, 373 septum, 313, 373 Naso-lacrimal duct, 384 Naso-turbinal anlage, 376 Navel, 70 Neck, muscles of, 317 Neopallium, 346 Nephrogenic cords, 197, 201 tissue, 120, 136, 202 Nephrostome, 195 Nephrotome, 195 chick, 40, 52, 64 Nerve, abducens, 116, 361 accessorius, 116 acoustic, 92, 116, 358 auditory, 358 axillary, 356 cells, 300 cerebral, 115, 357 facial, 92, 116, 362, 363 femoral, 356 fibers, 300 cell-chain theory of development, 306 layer, 382 glossopharyngeal, 93, 116, 362, 364 hypoglossal, 93, 116, 151, 360 mandibular, 116, 361 maxillary, 116, 361 median, 356 motor somatic, 360 musculocutaneous, 356 obturator, 356 oculomotor, 92, 115, 330, 360 olfactory, 357 ophthalmic, 116, 361 optic, 115, 358, 383 peroneal, 356 petrosal, superficial, 116, 363 phrenic, 355 radial, 356 recurrent laryngeal, 264 INDEX Nerve, sciatic, 356 sensory, somatic, 357 somatic, motor, 360 sensory, 357 spinal, 116, 353 accessory, 93, 116, 364 efferent or ventral root fibers of, 302 terminal, 358 tibial, 356 trigeminal, 92, 116, 361 trochlear, 116, 330, 361 ulna, 356 vagus, 93, 116, 362, 364 visceral mixed, 361 Nervous layer of retina, 126 system, 91, 114 central, 321 chick, 44, 55 human, 80, 321 peripheral, 353 sympathetic, 366 tissue, histogenesis of, 300 Neural crest, 50, 93, 304 chick, 41 folds, 38, 40 groove, 38, 300 plate, 300 tube, 38, 40, 64, 300, 332 anomalies of, 352 origin of, 29, 30 supporting cells of, 307 Neurenteric canal, 31, 32, 33, 76 Neurilemma, 306 Neuroblasts, 302 differentiation of, into neurones, 302 of retina, 382 Neurofibrilla, 304 Neuroglia cells, 300, 302, 307, 308 fibers, 300, 302, 307, 308 Neurokeratin, 306, 308 Neuromeres, 44, 104, 115, 334 Neurones, 302 afferent, 305 differentiation of neuroblasts into, 302 theory, 305 Neuropores, 40, 321 anterior, 43 Neutrophiles, 246 Nipple, 298 Node, primitive (of Hensen), 51 of Ranvier, 306 Nodose ganglion, 116 Nodulus cerebelli, 337 Normoblasts, 244 Nose, 371 Notochord, 33, 38, 309 chick, 40, 64 origin of, 29, 35 Notochordal canal, 33 plate, 31, 32, 37, 38 Nuclear zone, 302 Nuclei pulposi, 35, 309 Nucleolus, 7 Nucleus ambiguus, 364 caudate, 345 cuneatus, 335 dentate, 337 gracilis, 335 lenticular, 345 Nucleus of pons, 336 olivary, 335 receptive, 335 red, 337 ruber, 337 terminal, 335 Nuck’s diverticula, 224 Nymphe, 227 OBEX, 334 Obturator membrane, 316 nerve, 356 Occipital bone, ossification of, 312 Oculomotor nerve, 92, 115, 330, 360 Odontoblasts, 157 Olfactory apparatus, 346 brain, 328 epithelium, 128 fossa, 371, 372 lobe, 346 nerve, 357 organ, 371 pits, 112, 371, 372 pig, 89 placodes, 371 stalk, 346 tracts, 346 Olivary nucleus, 335 Omental bursa, 189 inferior recess of, 190 Omentum, 133, 169, 180, 191, 192 Odécyte, 18 primary, 18 Oégenesis, 8 Oégonia, 18 Operculum, 349 Ophthalmic nerve, 116, 361 vein, 273 Optic chiasma, 329, 358 cup, 56, 112, 328, 376, 381 nerve, 115, 358, 382 placode, 376 recess, 330, 343 stalks, 47, 59, 376 tract, 358 vesicles, 40, 43, 47, 59, 343 Ora serrata, 381 Oral cavity, 142 Orbital operculum, 349 Organ, Corti’s, 359, 386 Jacobson’s, 357, 374 spiral, 386, 387 vomero-nasal, 357, 374 Os coxe, 316 Ossicles, auditory, 389 Ossification of carpus, 316 of chondrocranium, 312 of ethmoid bone, 313 of femur, 316 of fibula, 316 of humerus, 316 of ilium, 316 of ischium, 316 of metatarsus, 316 of occipital bone, 312 of patella, 316 of phalanges, 316 of pisiform, 316 INDEX 405 Ossification of pubis, 316 of radius, 316 of skull, 312 of sphenoid bone, 313 of tarsus, 316 of temporal bone, 313 of tibia, 316 of ulna, 316 of vertebre, 310 Osteoblasts, 288, 289 Osteoclasts, 289 Ostium abdominale, 210 vagina, 221 Otic ganglia, 368 vesicle, 45 Otocyst, 45, 56, 60, 80, 92, 385 Ovarian arteries, 267 pregnancy, 20 vein, 275 Ovary, 214 anomalies, 218 compared with testis, 217 descent of, 222 mediastinum, 214 proper ligament of, 221 septula, 214 stroma of, 215 Ovulation, 10 Ovum, cleavage of, 23. See also Cleavage of ovum. human, 7 fertilization of, 20 implantation of, 231 isolecithal, 23 maturation of, 17, 18 mouse, fertilization of, 19 segmentation of, 23. See also Cleavage of ovum. structure of, amphibian, 7 bird, monkey, 10 telolecithal, 23 PALATE bones, 314 cleft, 149 development of, 146 premaxillary, 373 primitive, 373 soft, 149 Palatine processes, lateral, 147 tonsil, 82, 118, 162 Pallium of cerebral hemispheres, 329 of cerebrum, 341 Pancreas, alveoli of, 179 human, 81, 178 accessory duct of, 179 islands of, 179 pig, 96, 120 Pancreatic duct, 179 Papille, dental, 153, 157 hair, 296 of tongue, 151, 152 renal, 202 Papillary ducts, 201 muscles, 259 Paradidymis, 199, 218 Parathyreoid gland, 82, 118, 163 Paraurethral ducts, 227 Parietal pleura, 168 Parietals, 314 406 Parieto-occipital fissure, 351 Parolfactory area, 346 Parodphoron, 199, 219 Parotid glands, 152 Pars ceca, 381 ciliaris, 382 iridis retine, 382 lateralis of sacrum, 311 optica, 381, 382 hypothalamica, 339 radiata, 202 Parthenogenesis, artificial, 20 Patella, ossification of, 316 Peduncles of cerebrum, 338 Pelvis, renal, 199, 201 Penis, 143 Perforated space, 346 Pericardial cavity, 49, 53, 179, 180 chick, 53, 60 membrane, 187 Perichondral bone formation, 289, 290 Perichondrium, 287 Periderm, 294 Perilymph space, 387, 389 Periosteal bone formation, 289 lamelle, 290 Periosteum, 287 Periotic capsule, 312 Peripheral lymphatics, 279 nervous system, 353 sinus, 281 Periportal ducts, 177 Peritoneal cavity, 53, 185 chick, 53 mesothelium, 170 sac, 133 lesser, 133, 189 Peritoneum, 133 Peroneal artery, 268 nerve, 356 Petrosal ganglion, 93, 116, 364 nerve, superficial, 116, 363 sinus, 273 Pfliiger’s tubes, 215 Phalanges, ossification of, 316 Phallus, 143, 225 Pharyngeal bursa, 162 membrane, 42, 46, 47, 80, 159 plate, 42 pouches, 46, 60, 95, 117, 160 tonsil, 162 Pharyngopalatine arches, 149 Pharynx, human, 81 muscles of, 320 pig, 93, 116 Philtrum, 146 Phrenic artery, 267 nerve, 355 Pia mater, 126 Pig embryos, 112 6 mm., 89 10 to 12 mm., 112 dissection of, 137 transverse sections of 6 mm., 104 of 10 mm., 125 fetal membranes, 68 Pigment granules, 295 layer of retina, 126, 377, 381 Pillars, anterior, of fornix, 347 INDEX Pillars of Corti, 387 Pineal body or gland, 141, 290, 310, 330, 339 Pisiform, ossification of, 316 Pituitary body, 339 Placenta, accessory, 242 human, 73, 230, 231, 235, 237 cotyledons of, 240 intervillous spaces of, 241 position of, 242 relation of fetus to, 241 vessels of, 241 previa, 242 succenturiate, 242 Placodes, 362 auditory, 385 olfactory, 371 optic, 376 Plasm, germ, continuity of, 4 Plate, alar, 323, 332, 335, 337 basal, 239, 240, 323, 332 blood, 247 closing, 160 cribriform, 313 cutis, 111 floor, 322, 324, 332 lens, 376 muscle, 111 neural, 300 notochordal, 31 roof, 322, 332, 338 urethral, 225 Pleura, parietal, 168 visceral, 168 Pleural cavity, 53, 61, 183, 185 chick, 53 coelom, 96 Pleuro-pericardial cavity, 40 membranes, 182, 183 Pleuro-peritoneal canal, 183 cavities, 179 membranes, 182, 183 Plexus, brachial, 355 chorioid, 141, 142, 334, 338, 342 lumbo-sacral, 356 Plica semilunaris, 383 vene cave, 103, 133, 189, 192, 274 vein of, 274 Polar bodies, 18 Polocytes, 18 Polydactyly, 316 Polymorphonuclear leucocytes, 246 Rely payeuc theory of origin of blood elements, 43 Polyspermy, 20 Pons, 115, 330 nucleus of, 336 Pontine flexure, 327 Popliteal artery, 268 Portal circulation, 279 vein, 99, 125, 268, 270 Postbranchial bodies, 164 Postnasal gut, 97 Preformation, doctrine of, 2 Tregnancy, abdominal, 20 ovarian, 20 tubal, 20 uterine glands of, 236 uterus during, 230 Premaxillary palate, 373 INDEX Premyelocytes, 244, 245, 246 Prepucium, 225, 226 Prevertebral ganglia, 368 Primary excretory ducts, 52, 196, 199 Primates, 68 cleavage of ovum in, 27 Primitive choane, 373 folds, 31 groove, 31, 36, 38 heart, chick, 42 knot or node, 31, 36, 51 palate, 373 pit, 31 segments, 2, 40 streak, 31, 36, 40, 51 Primordial follicles, 215 Proamniotic area, 39, 43 Process, coracoid, 316 costal, 310 fronto-nasal, 372 lateral nasal, 144, 145, 372 palatine, 147 mandibular, 112, 314, 372 mastoid, 314 maxillary, 112, 314, 372 median nasal, 144, 145, 372, 373 palatine, 147 nasal, 372 styloid, 314, 315 vermiform, 172, 174 xiphoid, 311 cleft, 316 Processus globulares, 372 Pronephric ducts, 196 tubules, 49 Pronephros, 52, 195 Pronucleus, 18, 19 Prophase of mitosis, 13 Prosencephalon, 327 chick, 44 Prostate gland, 227 Prostatic utricle, 218, 219 Pubis, ossification of, 316 Pulmonary arteries, 99, 121, 122, 168, 258, 262, 264 ridge, 183 vein, 121, 168, 255 Pulp, dental, 157 enamel, 155 Pupillary membrane, 381 Pyramids of kidney, 201 QuapraTE lobe of liver, 192 Rapist artery, 268 nerve, 356 Radius, ossification of, 316 Ramus angularis, 270 arcuatus, 270 communicans, 354, 366 dorsal, 354 gray, 367 lateral, 354 posterior, 354 terminal, 354 ventral, 354 white, 366 Ranvier’s nodes, 306 407 Rathke’s pocket, 57, 59, 81, 93, 126, 160 Recapitulation, law of, 5 Receptive nucleus, 335 Recess, inferior, of omental bursa, 190 lateral, 334 mammillary, 330, 341 optic, 330, 343 Rectum, 120, 135, 143, 174, 205 Red blood corpuscles, 244, 245 bone marrow, 289 nucleus, 337 Reference, titles for, 6 Regeneration of bone, 291 Reichert’s cartilage, 390 Reil’s islands, 349 Reissner’s membrane, 389 Renal artery, 205, 267 columns, 202 corpuscles, 133, 198, 199 papilla, 202 pelvis, 199, 201 tubules, 201, 203 veins, 275 Reptiles, cleavage of ovum in, 26 gastrulation of, 28 origin of mesoderm in, 30 Respiratory epithelium, 168 Rete ovarii, 214, 217 testis, 212 Reticular formation, 335 tissue, 163, 285 Retina, layers of, 382 nervous layer, 126 pigment layer of, 126, 377, 381 Retinal layer, 381 of optic cup, 377 Retroperitoneal sac, 279 Rhinencephalon, 328, 341, 346 Rhombencephalon, 80, 327 chick, 44 Rhombic grooves, 334 lip, 334 Rhomboidial sinus, 40, 44, 50 Ribs, 309, 310 Ridge, pulmonary, 183 Rod cells of retina, 382 Rolando’s fissure, 351 Roof plate, 322, 332, 338 Roots, spinal, dorsal, 305 Round ligament, 220, 222 SACCcULUS, 386 Saccus vaginalis, 223 Sacral artery, middle, 268 Sacrum, pars lateralis of, 311 Sagittal dissections, median, 140 sinus, superior, 273 Salivary glands, 152 Saphenous vein, 277 Sarcolemma, 293 Sarcoplasm, 293 Sarcostyles, 293 Satyr tubercle, 391 Sauroid blood cells, 244 Scala tympani, 389 vestibuli, 389 Scapula, ossification of, 316 Sciatic nerve, 356 408 Sclerotic layer of eye, 383 Sclerotome, 111, 284 Scrotal area, 227 Scrotum, 227 ligament of, 222 Sebaceous gland, 296 Sections, chick, fifty hours, 59 thirty-eight hours, 47 twenty-five hours, 40 pig, 6 mm., 104 10 mm., 125 Seessel’s pocket, 35, 81, 93, 160 Segmental zone, 64 Segmentation of ovum, 23. ovum. of vertebrate head, 365 Segments, mesodermal, 2, 40, 51, 62, 64 primitive, 2 Semilunar ganglion, 92, 116, 361 valves, 258 Seminal vesicle, 218 Sense cells, 387 organs, chick, 44, 55 human, 80, 370 Sensory nerves, somatic, 357 organs, general, 371 Septa placenta, 240 Septum, atrial, 251 interventricular, 121, 258 median, of adult spinal cord, 324, 325 membranaceum, 259 nasal, 313, 373 pellucidum, 346, 347 primum, 98, 120, 252, 279 scroti, 227 secundum, 121, 253, 279 spurium, 253 transversum, 61, 62, 83, 113, 116, 143, 175, 180, 182, 183 Sertoli, sustentacular cells of, 14, 213 Sex cells, 208 determination of, 22 Shaft of hair, 296 Sheath cells, 306 hair, 296 medullary, 306 myelin, 306 Shoulder-blade, ossification of, 316 Sinus, blood, 281 cavernosus, 273 cervical, 90, 112 coronary, 253, 271 frontal, 376 marginal, 241 maxillary, 376 peripheral, 281 petrosal, 273 rhomboidal, 40, 44, 50 sagittal, superior, 273 sphenoidal, 376 transverse, 273 urogenital, 120, 205, 212 venosus, 57, 60, 97, 120, 249, 250, 253 valves of, 121, 251 Sinusoids, 86 of liver, 57, 62, 176, 268, 269 Situs viscerum inversus, 194 Skeletal muscle, striated, 291, 292 system, 309 See also Cleavage of INDEX Skeleton, 309 anomalies of, 316 appendicular, 315 axial, 309 branchial arch, 314 Skull, 311 chondrification of, 312 membrane bones of, 314 ossification of, 312 Smooth muscle, 291 Solitary tract, 362 Soma, 4 Somatic mesoderm, 52, 53, 69 motor nerves, 360 sensory nerves, 357 Somatopleure, 30, 33, 52, 53, 62, 64 Somites, 2 Sperm cells, 10 Spermatic artery, 267 cord, 224 veins, 275 Spermatids, 14 Spermatocyte, primary, 14 secondary, 14 Spermatogenesis, 14 Spermatogonia, 14, 213 Spermatozoon, 10 Sphenoid bone, ossification of, 313 Sphenoidal sinus, 376 Spheno-mandibular ligament, 315 Spheno-palatine ganglia, 368 Sphincter muscle of iris, 383 Spina bifida, 352 Spinal accessory nerve, 93, 116, 364 arteries, 264 cord, 322 primitive segments, section through, 111 ganglia, 50, 116, 304 supporting cells, 305, 306 nerves, 116, 353 efferent or ventral root fibers of, 302 roots, dorsal, 305 tract, descending, of trigeminal nerve, 361 Spiral ganglia, 358, 359 limbus, 387 organ, 386, 387 sulcus, 387 tunnel, 387 Spireme, 13 Splanchnic mesoderm, 53, 69, 169, 366 Splanchnopleure, 30, 34, 52, 53, 64 Spleen, 191, 281 Splenic corpuscles, 282 Spongioblasts, 302, 306, 307 Spongy layer, 236, 240 Stapedial artery, 390 muscle, 390 Stapes, 315, 390 Stenson’s canal, 148 Sternal bars, 311 Sterno-cleido-mastoid muscle, 364 Sternum, 311 cleft, 316 Stoerck’s loop, 203 Stomach, 81, 96, 119, 169 Stomodeum, 57, 80, 161 Stratified epithelium, 294 Stratum corneum, 294 germinativum, 294 Stratum granulosum, 216, 217, 294 lucidum, 294 Stroma of ovary, 215 Study, methods of, 5 Stylo-hyoid ligament, 315 Styloid process, 314, 315 Subcardinal veins, 102, 123, 124, 274 Subclavian arteries, 99, 122, 262, 263, 266, 268 veins, 123, 276 Sublingual gland, 152 Submaxillary ganglia, 368 gland, 152 Substantia ossea, 157 propria of cornea, 377 Sudoriparous glands, 297 Sulcus, central, 351 coronary, 225, 251 hypothalamicus, 330, 339 interventricular, 258 limitans, 323, 332, 339 of cerebrum, 351 spiral, 387 Supporting cells, 371, 387 of neural tube, 307 of spinal ganglia, 305, 306 tissue, 285 Suprarenal artery, 267 gland, 143, 368, 369 accessory, 370 vein, 275 Supratonsillar fossa, 161 Suspensory ligament of lens, 381 Sustentacular cells (of Sertoli), 14, 213 Sweat glands, 297 Sylvian fissure, 349 Sympathetic ganglia, 305, 367 nervous system, 366 Synovial membrane, 291 TACTILE corpuscles, 371 Tenia, 334 Tail bud, 55 fold, 55 gut, 97 of caudate nucleus, 345 Tarsal glands, 383 Tarsius, origin of mesoderm in, 34 Tarsus, 383 ossification of, 316 Taste buds, 151, 371 cells, 371 Teeth, anlages of, 153, 154 anomalies of, 158 cement of, 157 decidual, periods of eruption, 157 dental lamina of, 153 papilla, 153, 157 pulp, 157 sac, 157 dentine, 157 development of, 153 enamel, 153, 155 milk, periods of eruption, 157 odontoblasts, 157 of vertebrates, 158 permanent, periods of eruption, 158 Tegmentum, 330 Tela chorioidea, 329, 338 INDEX 409 Telencephalon, chick, 56 commissures of, 346 human, 80, 327, 341 pig, 92, 115 Telolecithal ova, 23 Telophase of mitosis, 13 Temporal bone, ossification of, 313 operculum, 349 Tendon, 286 Tensor nerve, 358 nucleus, 335 ramus, 354 tympani, 390 ventricle, 326 Testis, 212 anomalies of, 214 compared with ovary, 217 concealed, 224 cords, 212, 213 descent of, 222 intermediate cords of, 213 interstitial cells of, 213 ligament of, 221 mediastinum, 213 tubuli contorti, 213 recti, 213 septula, 213 Tetrads, 16 Thalamus, 142, 330 Thebesian valve, 254 Theca folliculi, 217 Theory of concrescence, 31 Thoracic duct, 279 Thoraco-abdominal muscles, 317 Thymic corpuscles, 163 Thymus, 162 anlages, 82 gland, 118 Thyreo-cervical trunk, 266 Thyreoglossal duct, 117, 164 Thyreoid anlage, 60 cartilage, 166, 315 gland, 118, 164 human, 81, 82, 164 pig, 94, 95 Tibia, ossification of, 316 Tibial nerve, 356 veins, 277 Tissue, adipose, 287 areolar, 286 connective, 285 white fibrous, 285 corneal, 286 differentiation of, 4 elastic, 286 lymphoid, of spleen, 282 nervous, 300 reticuldr, 163, 285 supporting, 285 Titles for reference, 6 Toes, supernumerary, 316 Tomes, dentinal fibers of, 157 Tongue, muscles of, 320 of pig, 116, 143, 149 papille of, 151, 152 Tonsil, palatine, 82, 118, 162 pharyngeal, 162 Tonsillar fossa, 161 Touch-pads, 300 410 Trabecule carne, 259 Trachea, human, 81, 82, 164, 166 pig, 94, 95, 119, 143 Tract, descending, of fifth nerve, 335 Tractus solitarius, 335 Tragus, 391 Trapezius muscle, 364 Triangular ligaments, 192 Tricuspid valves, 121, 259 Trigeminal nerve, 92, 116, 361 Trochlear nerve, 116, 330, 361 Trophectoderm, 26, 71, 72, 232 Trophoderm, 232, 234 Tubal pregnancy, 20 Tuber cinereum, 330, 341 Tubercle, cloacal, 225 Darwin’s, 391 genital, 225 Miiller’s, 221 satyr, 391 Tuberculum acusticum, 358 impar, 82, 94, 117, 150 Tubular heart, 248 Tubules, mesonephric, 197 and genital glands, origin of, 218 renal, 120, 201, 203 Tubuli contorti, 213 recti, 213 septula, 213 Tunica albuginea, 212, 214 externa, 217 interna, 217 vaginalis, 224 Turbinate anlages, 143 Twins, development of, 21 Tympanic cavity, 161, 389 membrane, 117, 391 ULNA, ossification of, 316 Ulnar artery, 268 nerve, 356 Ultimobranchial body, 118, 164 Umbilical arteries, 86, 99, 123, 135, 260, 267 cord, human, 70 of pig, 70 hernia, 70 veins, 259, 261, 268, 271 human, 86 pig, 100, 124 vessels, 70 Umbilicus, 70 Unguiculates, 68 Ungulates, 68 Unipolar ganglion cells, 305 Urachus, 77, 208 Ureter, 120, 135, 199, 208 Urethra, 143, 205, 227 Urethral groove, 225 plate, 225 Urogenital ducts, 144 fold, 197, 208 glands, 144 membrane, 160, 205 opening, 225 organs, 83, 143 sinus, 120, 205, 212 system, 97, 120, 195 Uterine glands of pregnancy, 236 INDEX Uterine tubes, 219 Utero-vaginal anlage, 220 Uterus, 219, 220 anomalies of, 221 bicornis, 221 during menstruation, 230 pregnancy, 230 fetalis, 221 fundus of, 220 growth of, 221 infantilis, 221 ligaments of, 221, 222 masculinus, 219 planifundus, 221 Utricle, prostatic, 218, 219 Utriculus, 386 Uvula, 149 Vacina, 219, 220 anomalies of, 221 fornices of, 220 masculina, 218, 219 Vagus ganglia, accessory, 116 nerve, 93, 116, 362, 364 Vallate papilla, 151 Valves, atrio-ventricular, 259 bicuspid, 121, 259 colic, 174 Eustachian, 254 mitral, 259 of coronary sinus, 254 of inferior vena cava, 254 of sinus venosus, 121, 251, 253, 254 semilunar, 258 Thebesian, 254 tricuspid, 121, 259 Vascular system, 243 Vegetal pole, 23 Veins, anterior cardinal, 49, 58, 59, 60, 86, 101, 123, 261, 268, 271 axillary, 276 azygos, 274 basilic, 276, 277 border, 276 brachial, 276 cardinal, 123 ane 49, 58, 59, 60, 86, 101, 123, 261, 268, common, 58, 60, 86, 101, 123, 261, 268, 271 left, 97 right, 97 posterior, 58, 62, 63, 86, 102, 123, 261, 268, 274 cephalic, 276, 277 cerebral, 273 Ea, 58, 60, 86, 101, 123, 261, 268, 1 left, 97 right, 97 development of, 268 femoral, 277 gluteal, 277 hemiazygos, 274 hepatic, 270 common, 98 iliac, 274, 275 intersegmental, 274 ischiadic, 274 jugular, 123, 273 INDEX Veins, linguo-facial, 101 lumbar, 276 mesenteric, superior, 99, 100, 125, 270 of extremities, 276 of heart, 86 of lower extremity, 277 of pig, 99, 123 of plica ven cave, 274 ophthalmic, 273 ovarian, 275 portal, 99, 125, 268, 270 posterior cardinal, 58, 62, 63, 86, 102, 123, 261, 268, 274 pulmonary, 121, 168, 255 renal, 275 saphenous, 277 spermatic, 275 subcardinal, 102, 123, 124, 274 subclavian, 123, 276 suprarenal, 275 tibial, 277 umbilical, 259, 261, 268, 271 human, 86 pig, 100, 124 vitelline, 49, 62, 86, 99, 124, 182, 260, 268 chick, 39, 40, 42 right, 98 Velum, medullary, 330, 337 Vena anonyma, left, 271 right, 272 capitis lateralis, 273 medialis, 271, 273 cava, inferior, 100, 103, 120, 124, 189, 274, 275 superior, 271 porte, 268,270 Ventral arteries, 99, 122 ramus, 354 Ventricle, fifth, 347 ° first, 329 fourth, 115, 330 lateral, 115, 329 of heart, 57, 83, 90, 97, 249, 251, 258 of larynx, 165 second, 329 terminal, 326 third, 329, 341 Ventricular limb, 249 Ventro-lateral arteries, 99, 122 Vermiform process, 172, 174 Vermis cerebelli, 336 Vernix caseosa, 74, 295 Vertebre, 309, 310 chondrification of, 310 ossification of, 310 pig, centra of, 142 variations in number, 316 Vertebral arch, 310 arteries, 122, 264 Vertebrate head, segmentation of, 365 Vesicle, auditory, 385 blastodermic, 26 brain, primary, 322, 327 4Il Vesicle, cervical, 161 lens, 376, 379 optic, 40, 43, 47, 59, 343 otic, 45 seminal, 218 Vesicular follicles, 215 Vestibular anlage, 386 ganglia, 358 glands, 228 membrane, 389 Villi, anchoring, 237 of chorion, 71, 72, 232, 237 of intestine, 173 origin of, 72 Viscera, 114 lateral dissections, 138 pig, dissections of, 91 Visceral ganglia, 368 mixed nerves, 361 pleura, 168 Vitelline arteries, 46, 58, 63, 86, 99, 122, 260, 261, 262 chick, 42 circulation, 46 duct, 159 membrane, 7 veins, 49, 62, 86, 99, 124, 182, 260, 268 chick, 40 right, 98 Vitello-umbilical trunk, 86, 260 Vitreous body of eye, 380 Voluntary muscle, 52 Vomer, 314 Vomero-nasal organ, 357, 374 Wate blood corpuscles, 245. See also Leucocytes. commissure, 325 fibrous connective tissue, 285 rami, 366 Whole embryos for study, 137 Winslow’s foramen, 134, 190 Wolffian ducts, 97, 83 XIPHOID process, 311 cleft, 316 YELLOW bone marrow, 290 Yolk, 7 sac, 65, 66, 67, 68, 77 stalk, 65, 66, 77, 79, 120, 159, 170, 171 ZONA pellucida, 7 Zone, ependymal, 301 marginal, 302 nuclear, 302 segmental, 64 Zonula ciliaris, 381 Zuckerkand!’s bodies, 369 Zygomatic bone, 314 DWAR he St ICI ale Ps LOH NNp RSH iy Pees yy yay i CVA, GG i) ND wy i x Hi SMC Sr he OM ats LS MOO aY Ph ate ARROW ROR Ne: oh OU ar (x Nn arses seats ey sot ett Opn mtn Pit wy ph ig ys , A OUN HP RRO RY en On i SRN PATA ATOrOu re Mo oe Para uy twat Oa) Lan