Jvffv < ^ v/ (v * a-. '^ ^X"-^ ' New York State College of Agriculture At Cornell University Ithaca, N. Y. Library Cornell University Library QM 601.M19 1920 The development of the human body; a manu 3 1924 003 122 250 Cornell University Library The original of tiiis book is in tine Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924003122250 THE DEVELOPMENT OF THE HUMAN BODY McMURRICH MORRIS'S ANATOMY FIFTH EDITION UNDER AMERICAN EDITORSHIP Rewritten, Revised, Improved, with Many New Illustrations EDITED BY C. M. JACKSON, M. S., M. D. Professor and Director of the Department of Anatomy University of Minnesota Among the American contributors will be noted: C. M. Jackson, J. Playfair McMurrich, R. J. Terry, Irving Hardesty, Abram T. Kerr, Charles R. Bardeen, Eliot R. Clark, and H. D. Senior. F. W. Jones, John Morley, Peter Thomson, David Waterston head the English contributors. "The ever-growing popularity of the book with teachers and students is an index of its value, and it may safely be recommended to all interested."- — From The Medical Record, New York. The text has been completely revised. Very special attention, in this new edition, has been paid to the illustrations, with the result that the teaching value of the book has been materially increased. It contains many features of special advantage to students. It is modern, up to date in every respect. It has been carefully revised, and in many parts rewritten, and includes many new features. Containing riSa Illustrations, of which 358 are in colors. One Handsome Octavo Volume. Thumb Index. Cloth, $9.00. Or in Five Parts, as follows, each part sold separately: PART I. — -Morphogenesis. Osteology. Articulations. Index. $2.25. PART II. — Muscles. Blood — vascular System; Lymphatic System. $3.25. Part III. — Nervous System. Special Sense Organs. Index. $3.00. PART IV. — Organs of Digestion; of Voice and Respiration. Urinary and Repro- ductive Organs. Ductless Glands. Skin and Mammary Glands. Index. $2.25. PART V. — Clinical and Topographical .(Anatomy. Index. $2.25. THE DEVELOPMENT OF THE HUMAN BODY A MANUAL OF HUMAN EMBRYOLOGY BY J. PLAYFAIR McMURRlCH, A. M., Ph. D., LL. D. PROFESSOR OF ANATOMY IN THE UNIVERSITY OF TORONTO FORMERLY PROFESSOR OF ANATOMY IN THE UNIVERSITY OF MICHIGAN SIXTH EDITION, REVISED AND ENLARGED With Two Hundred and Ninety Illustrations Several of which are Printed in Colors PHILADELPHIA P. BLAKISTON'S SON & CO. 1012 WALNUT STREET Copyright, 1920, by P. Blakiston*s Son & Co. THK MAFIiB P » EJ S B T O H K PA PREFACE TO THE SIXTH EDITION The increasing interest in human and mammalian embryology which has characterized the last few years has resulted in many additions to our knowledge of these branches of science, and has necessitated not a few corrections of ideas formerly held. In this sixth edition of this book, as in previous ones, the attempt has been made to incorporate the results of all important recent contri- butions upon the topics discussed, and. at the same time, to avoid any considerable increase in the bulk of the volume. Several chapters have, therefore, been largely recast, and the subject matter has been thoroughly revised throughout, so that it is hoped that the book forms an accurate statement of our present knowledge of the development of the human body. In addition to the works mentioned ia the preface to the first edition as of special value to the student of Embryology, mention should be made of the Handhuch der vergleichenden und experimen- tellen Entwicklungslehre der Wirbeltiere edited by Professor Oscar Hertwig and especially of the Manual of Human Embryology edited by Professors F. Keibel and F. P. Mall. Univeesity op Toronto. PREFACE TO THE FIRST EDI'IION The assimilation of the enormous mass of facts which consti- tute what is usually known as descriptive anatomy has always been a difficult task for the student. Part of the difficulty has been due to a lack of information regarding the causes which have determined the structure and relations of the parts of the body, for without some knowledge of the why things are so, the facts of anatomy stand as so many isolated items, while with such knowl- edge they become bound together to a continuous whole and their study assumes the dignity of a science. The great key to the significance of the structure and relations of organs is their development, recognizing by that term the historical as well as the individual development, and the following pages constitute an attempt to present a concise statement of the development of the human body and a foundation for the proper understanding of the facts of anatomy. Naturally, the individual development claims the major share of attention, since its pro- cesses are the more immediate forces at work in determining the conditions in the adult, but where the embryological record fails to afford the required data, whether from its actual imperfection or from the incompleteness of our knowledge concerning it, recourse has been had to the facts of comparative anatomy as affording indications of the historical development or evolution of the parts under consideration. It has not seemed feasible to include in the book a complete list of the authorities consulted in its preparation. The short bibliographies appended to each chapter make no pretensions to completeness, but are merely indications of some of the more important works, especially those of recent date, which con- sider the questions discussed. For a very full bibliography of all works treating of human embryology up to 1893 reference VIU PREFACE TO THE FIRST EDITION may be made to Minot's Bibliography of Vertebrate Embryology, published in the "Memoirs of the Boston Society of Natural History," volume iv, 1893. It is fitting, however, to acknowledge an especial indebtedness, shared by all writers on human embryology, to the classic papers of His, chief among which is his Anatomic menschlicher Embryonen, and grateful acknowledge- ments are also due to the admirable text-books of Minot, 0. Hertwig, and Kollmann. Anatomical Laboratory, University of Michigan. CONTENTS ~, Faoe Introduction i PART I.— GENERAL DEVELOPMENT CHAPTER I The Spermatozoon and Spermatogenesis; the Ovum and Its Matu- ration and Fertilization ii CHAPTER II The Segmentation of the Ovum and the Formation of the Germ Layers , . . 41 CHAPTER III The Medullary Groove, Notochord, and Mesodermic Somites . . 67 CHAPTER IV The Development of the External Form of the Human Embryo 89 CHAPTER V The Yolk-stalk, Belly-stalk, and Fetal Membranes no PART IL— ORGANOGENY CHAPTER VI The Development of the Integumentary System 143 CHAPTER VII The Development of the Connective Tissues and Skeleton . . 155 CHAPTER VIII The Development of the Muscular System 195 ix X CONTENTS CHAPTER IX The Development of the Circulatory and Lymphatic System^. . 222 CHAPTER X The Development of the Digestive Tract and Glands 282 CHAPTER XI The Development of the Pericardium, the Pleuro-peritoneum, and the Diaphragm 319 CHAPTER XII The Development of the Organs of Respiration 334 CHAPTER XIII The Development of the Urinogenital System 341 CHAPTER XIV The Suprarenal System of Organs 374 CHAPTER XV The Development of the Nervous System 381 CHAPTER XVI The Development of the Organs of Special Sense 432 CHAPTER XVII Post-natal Development 475 Index 491 THE DEVELOPMENT OF THE HUMAN BODY INTRODUCTION One of the fundamental principles of biology is that which regards all organisms as composed of one or more structural units, termed cells. Each of these maintains an individual existence and in multicellular organism is influenced by its fellows and contri- butes with them to the maintenance of the general existence of the individual of which it is a part. This is the cell theory formulated by Schleiden and Schwann (1839), and according^to it the human body, though physiologically a unit, is, structurally, a community, an aggregate of many individual units, each of which leads to a certain extent an independent existence and yet both contributes to and shares in the general welfare of the community. To the founders of the theory the structural units were vesicles with definite walls, and little attention was paid to their contents. Hence the use of the term "cell" in connection with them. Long before the establishment of the cell theory, however, the existence of organisms composed of a gelatinous substance showing no indi- cations of a definite limiting membrane had been noted, and in 1835 a French naturalist, Dujardin, had described the gelatinous material of which certain marine organisms (Rhizopoda) are composed, terming it sarcode and maintaining it to be the material substratum which conditioned the various vital phenomena exhib- ited by the organisms. Later, in 1846, a botanist, von Mohl, I 2 INTRODUCTION observed that living plant cells contained a similar substance, upon which he believed the existence of the cell as a vital structure was dependent, and he bestowed upon this substance the name proto- plasm, by which it is now universally known. By these discoveries the importance originally attributed to the cell-wall was greatly lessened, and in 1864 Max Schultze reformu- lated the cell theory, defining the cell as a mass of protoplasm, the presence or absence of a limiting membrane or cell-wall being im- material. At the same time the spontaneous origination of cells from an undifferentiated matrix, believed to occur by the older authors, was shown to have no existence, every cell originating by the division of a preexisting cell, a fact concisely expressed in the aphorism of Virchow — omnis cellula a celluld. Interpreted in the light of these results, the human body is an aggregate of myriads of cells* — i.e., of masses of protoplasm, each of which owes its origin to the division of a preexistent cell and all of which may be traced back to a single parent cell — a fertilized ovum. All these cells are not alike, however, but just as in a social community one group of individuals devotes itself to the performance of one of the duties requisite to the well-being of the community and another group devotes itself to the perform- ance of another duty, so too, in the body, one group of cells takes upon itself one special function and another another. There is, in other words, in the cell-community a physiological division of labor. Thus certain cells become especially contractile, foriring muscle cells; others become especially irritable, responding readily to stimulation, and form nerve cells; others undertake the forma- tion of this or that secretion useful to the organism as a whole and are gland cells; while others set themselves apart for the reproduc- tion of the species. Each functional specialization is associated with a more or less definite structural adaptation, so that the general function of a cell may be recognized from its form and structure. The comparison of the cell-community to the social * It has been estimated that the number of cells entering into the composition of the body of an adult human being is about twenty-six million five hundred thousand millions. INTRODUCTION 3 community may thus be carried still further, for Just as gradations of individuality may be recognized in the individual, the municipal- ity, and the state, so too in the cell-community there are cells; tissues, each of which is an aggregate of similar cells; organs, which are aggregates of tissues, one^ however, predominating and determining the character of the organ; and systems, which are aggregates of organs having correlated functions. It is the province of embryology to study the mode of division of the fertilized ovum and the progressive differentiation of the re- sulting cells to form the tissues, organs, and systems. But before considering these phenomena as seen in the human body it will be well to get some general idea of the structure of an animal cell. This as has been already stated, is a mass of protoplasm, but, as a rule, one finds imbedded in this various products of its activi- ties, such as globules of fat, pigment, or secretion granules, all of which may be grouped together as deutoplasm (Fig. i) . The protoplasm itself is a viscous substance resembling egg-albumen in many of its physical peculiarities and like this being coagulated by heat or when it is exposed to the action of various chemical reagents. It is to be regarded as a colloidal mixture, whose principal constituents are albuminous and lipoid susbtances in varying proportions, the term protoplasm not connoting any defi- nite chemical compound, but being rather a morphological con- cept denoting all those colloidal complexes whose activities result in the manifestation of the phenomena which we term Life. The protoplasm of an animal cell is, however, by no means a homogeneous material. Even in the living cell what is termed a nucleus (Fig. i. A'') is usually clearly discernible as a more or less spherical body of a greater refractive index than the surround- ing protoplasm, and since this is a permanent organ of the cell it is convenient to distinguish the surrounding protoplasm as cyto- plasm from the nuclear protoplasm or karyoplasm. But the structure of the nucleus and other organs of the cell can be more accurately determined when the protoplasm has been "fixed" or coagulated by certain reagents and then subjected to the action of dyes which have a selective affinity for the various struc- 4 INTRODUCTION tural constituents. Treated thus both cytoplasm and karyoplasm present the appearance of a more solid reticulum forming a net- work in whose meshes is a more fluid material, the enchylema. At the surface of the cell the cytoplasmic reticulum passes over in o a more homogeneous layer, which may be distinguished even in the living cell by its greater firmness and resistence as compared with the more fluid central material. This surface pellicle is termed the ectoplasm (Fig. i, Ect) as distinguished from the central endoplasm (End) and there is a similar pellicle enclosing the karyoplasm, Pig. I. — Diagram Showing the Structure of a Cell. Ar, Archoplasm Sphere; cho, Chondriosome; cbr. Chromatin; Dp, Deutoplasm; Ect, Ecto- plasm; End, Endoplasm; N, Nucleus; n. Nucleolus. forming the nuclear membrane. In addition to the reticulum and enchylema the karyoplasm has scattered along the fibres of its reticulum a peculiar material termed chromatin and usually con- tains, embedded in its substance, one or more spherical bodies termed nucleoli, which may be merely larger masses of chromatin or bodies of special chemical composition. Further, in all actively growing cells there is differentiated in the cytoplasm a peculiar body known as the archoplasm sphere (Fig. i, Ar),m the center of which there is usually a minute spherical body, known as the centrosome, these structures playing an important part in the repro- duction of the cell by division. Finally there are also present INTRODUCTION 5 in the cytoplasm structures termed chondriosomes (Fig. i, Cko) which have the form of minute granules, mitochondria,, or rods, chondrioconts, and have been supposed by some observers to be concerned with the formation of special products of the cytoplasm, such as neurofibrils, secretion products, etc. It has been already stated that new cells arise by the division of preexisting ones, and this process is associated with a series of com- plicated phenomena which have great significance in connection with some of the problems of embryology. When such a cell as has been described above is about to divide, the fibers of the reticulum in the neighborhood of the archoplasm sphere arrange themselves so as to form fibrils radiating in all directions from the sphere as a center, and the archoplasm with its contained centro- some gradually elongates and finally divides, each portion retain- ing its share of the radiating fibrils, so that two asters, as the aggre- gate of centrosome, sphere and fibrils is termed, are now to be found in the cytoplasm (Fig. 2, A). Gradually the two asters separate from one another and eventually come to rest at opposite sides of the nucleus (Fig. 2, C). In this structure important changes have been taking place in the meantime. The nuclear membrane disappears and the chromatin, originally scattered irregularly along the reticulum, gradually aggregates to form a continuous thread (Fig. 2, A) and later this thread breaks up into a definite number of pieces, termed chromosomes (Fig. 2, B), the number of these being practically constant for each species of animal. The number occurring in man is probably twenty-four (Flemming, Duesberg, Wieman). As soon as the asters have taken up their position on opposite sides of the nucleus, the nuclear reticulum begins to be converted into a spindle-shaped bundle of fibrils which associate themselves with the astral rays and have lying scattered among them the chromosomes (Fig. 2, C). To the figure so formed the term amphiaster is applied, and soon after its formation the chromo- somes arrange themselves in a circle or plane at the equator of the spindle (Fig. 2, D) and the stages preparatory to the actual division, the prophases, are completed. O INTRODUCTION The next stage, the metaphase (Fig. 3, ^), consists of the divi- sion^ usually longitudinally, of each chromosome, so that the cell now contains twice as many chromosomes as it did previously. As soon as this division is completed the anaphases are inaugurated by the halves of each chromosome separating from one another and approaching one of the asters (Fig. 3, 5), and a group of chromo- FlG. -Diagrams Illustrating the Prophases of Mitosis. — {Adapted from E. B. Wilson.) somes, containing half the total number formed in the metaphase comes to lie in close proximity to each archoplasm sphere (Fig. 3 C). The spindle and astral fibers gradually resolve themselves again into the reticulum and the chromosomes of each group become irregular in shape and gradually spread out upon the nuclear reticulum so that two nuclei, each similar to the one from INTRODUCTION which the process started, are formed (Fig. i, D). Before all these changes are accomplished, however, a constriction makes its appearance at the surface of the cytoplasm (Fig. 3, C) and, gradually defpening, divides the cytoplasm in a plane passing through the equator of the amphiaster and gives rise to two separate cells (Fig. z, D). Fig. 3. — Diagrams Illustrating the Metaphase and Anaphases of Mitosis. — (Adapted from E. B. Wilson.) This complicated process, which is known as karyokinesis or mitosis, is the one usually observed in dividing cells, but occasion- ally a cell divides by the nucleus becoming constricted and divid- ing into two parts without any development of chromosomes, spindle, etc., the division of the cell following that of the nucleus. This amitotic method of division is, however, rare, and in many 8 INTRODUCTION cases, though not always, its occurrence seems to be associated with an impairment of the reproductive activities of the cells. In actively reproducing cells the mitotic method of division may be regarded as the rule. Since the process pf development consists of the multiplication of a single original cell and the differentiation of the cell aggregate so formed, it follows that the starting-point of each line of indi- vidual development is to be found in a cell which forms part of an individual of the preceding generation. In other words, each in- dividual represents one generation in esse and the succeeding gene- ration in posse. This idea may perhaps be made clear by the following considerations. As a result of the division of a fertilized ovum there is produced an aggregate of cells, which, by the physio- logical division of labor, specialize themselves for various func- tions. Some assume the duty of perpetuating the species and are known as the sexual or germ cells, while the remaining ones divide among themselves the various functions necessary for the main- tenance of the individual, and may be termed the somatic cells. The germ cells represent potentially the next generation, while the somatic cells constitute the present one. The idea may be represented schematically thus: First generation Somatic cells + germ cells II Second generation Somatic cells -|- germ cells II Third generation Somatic cells + germ cells, etc. It is evident, then, while the somatic cells of each generation die at their appointed time and are differentiated anew for each gene- ration from the germ cells, the latter, which may be termed collec- tively the germ-plasm, are handed on from generation to generation without interruption, and it may be supposed that this has been INTRODUCTION 9 the case ah initio. This is the doctrine of the continuity of the germplasm, a doctrine of fundamental importance on account of its bearings on the phenomena of heredity. It is necessary, however, to fix upon some link in the continuous chain of the germ-plasm as the starting-point of the development of each individual, and this link is the fertilized ovum. By this is meant a germ cell produced by the fusion of two units of the germ- plasm. In many of the lower forms of life {e.g. Hydra and certain turbellarian worms) reproduction may be accomplished by a di- vision of the entire organism into two parts or by the separation of a portion of the body from the parent individual. Such a method of reproduction is termed non-sexual. Furthermore in a nvunber of forms {e.g., bees. Phylloxera, water-fleas) the germ cells are able to undergo development without previously being fertilized, this con- stituting a method of reproduction known as parthenogenesis. But in all these cases sexual reproduction also occurs, and in all the more highly organized animals it is the only method that normally occurs; in it a germ cell develops only after complete fusion with another germ cell. In the simpler forms of this process little difference exists between the two combining cells, but since it is, as a rule, of advantage that a certain amount of nutrition should be stored up in the germ cells for the support of the developing embryo until it is able to secure food for itself, while at the same time it is also advantageous that the cells which unite shall come from differ- ent individuals (cross-fertilization), and hence that the cells should retain their motility, a division of labor has resulted. Certain germ cells store up more or less food yolk, their motility becoming thereby impaired, and form what are termed the female cells or ova, while others discard all pretensions of storing up nutri- tion, are especially motile and can seek and penetrate the inert ova; these latter cells constitute the male cells or spermatozoa. In many animals both kinds of cells are produced by the same indi- vidual, but in all the vertebrates (with rare exceptions in some of the lower orders) each individual produces only ova or spermato- zoa, or, as it is generally stated, the sexes are distinct. It is of importance, then, that the peculiarities of the two lO INTRODUCTION forms of germ cells, as ihe^r occur in the human species, should be considered. LITERATURE R. Chambers: "Microdissection Studies." Amer. Jour. Physiol., xliii, ipi?; and Jour. Exper. Zool., xxiii, 191 7. E. V. Cowdry: "The general functional significance of mitochondria'' Amer. Jour. Anat., xix, 1916, J. Duesberg: "Plastosomen, Apparato reticolare interno, und Chromidial- apparat," Ergeb. Anat. ti. Emtw., xx, 1911. J. Duesberg: "On the Present Status of the Chondriosome Problem." Biol. Bull, xxxvi, 1919. O. Hertwig: "Die Zelle und die Gewebe." Jena, 1893. H. L. WiEMAN: "Chromosomes in Man" Amer. Jour, Anal., xiv, 1913. E. B. Wilson: "The Cell in Development and Inheritance." Third edition New York, 1900. PART I GENERAL DEVELOPMENT CHAPTER I THE SPERMATOZOON AND SPERMATOGENESIS; THE OVUM AND ITS MATURATION AND FERTILIZATION The Spermatozoon. — The human spermatozoon (Figs. 4 and 5) is a minute and greatly elongated cell, measuring about 0.05 mm. in length. It consists of an anterior broader portion or head (Fig. 5, H), which measures about 0.005 m™- i^i length and, when viewed from one surface (Fig. 4, i), has an oval outline, though since it is somewhat flattened or concave toward the tip, it has a pyriform shape when seen in profile (Fig. 4, 2). Covering the flattened portion of the head and fitting closely to it is a delicate cap-like membrane, the head-cap (Fig. 5, H.C.), whose apex is a sharp edge, this structure corresponding to a pointed prolongation of the cap found in the spermatozoon of many of the lower vertebrates and known as the perforatorium. Immediately behind the head is a short portion known as the neck (Fig. 5, N), which consists of an upper more refractive body, the anterior nodule, and a lower clearer portion. To this succeeds the connecting or middle-piece (Figs. 4, m and 5, M) which begins with a posterior nodule, from the center of which there passes back through the axis of the piece an axial filament, enclosed within a sheath, this latter having wrapped around it a spiral filament. At the lower end of the middle piece this spiral filament terminates in the annulus,through which the axial filament and its sheath passes into the flagellum or tail (Fig. 4, /). This portion, which constitutes about four-fifths 12 THE SPERMATOZOON of the total length of the spermatozoon is composed simply of the axial filament and its sheath, this latter gradually thinning out as it passes backward and ceasing altogether a short distance above the end of the axial filainent. The filament thus projects some- FiG. 4. — Human Spermatozoon. I, Front view; 2, side view of the head; e, terminal filament; ft, head; /, tail; m, middle-piece. — (Afler Retzius.) Fig. 5. — Diagram Showing the Structure OF A Human Spermatozoon. Af, Axial filament; An, annulus; H, head; H. C, lower border of head-cap; M, middle- piece; N, neck; Na and Np, anterior and pos- terior nodule; S, sheath of axial filament ; 5^/, spiral filament. — {Bonnet, after Meves.) what beyond the actual end of the tail, forming what is known as the terminal filament or end-piece (Fig. 4, e) . To understand the significance of the various parts entering into the composition of the spermatozoon a study of their develop- ment is necessary, and since the various processes of spermatogene- sis have been much more accurately observed in such mammalia as the rat and guinea-pig than in man, the description which follows will be based on what has been described as occurring in these forms. From what is known of the spermatogenesis in man it SPERMATOGENESIS 13 seems certain that it closely resembles that of these mammals so far as its essential features are concerned. Spermatogenesis. — -The spermatozoa are developed from the cells which line the interior of the seminiferous tubules of the testis. The various stages of development cannot all be seen at any one part of a tubule, but the formation of the spermatozoa seems to sc^: sg- 1-sp D E Pig. 6. — Diagram Showing Stages gf Spermatogenesis as Seen in Differ- ent Sections of a Seminiperos Tubule of a Rat. 5C», spermatocyte of the first order; sc\ spermatocyte of the second order; 5g, spermatogonium; sp, spermatid; sz, spermatozoon. The Sertoli cells are stip- pXai.— {Adapted from Lenhossek.) pass along each tubule in a wave-like manner and the appearances presented at different points of the wave may be represented dia- grammatically as in Fig. 6. 14 SPERMATOGENESIS In section A of this figure four different generations of cells are represented; above are mature spermatozoa lying in the lumen of the tubule, while next the basement membrane is a series of cells from which a new generation of spermatozoa is about to develop. The cells of this series are of two kinds; the stippled one will develop into a structure known as a .S'crto/zce//, while the others, termed spermatogonia (sg) , are the parent cells of both spermatozoa and SertoH cells. The spermatogonia undergo several divisions before becoming the actual parent cells of the structures men- tioned, and it is found that about one in four of the ultimate sper- matogonia contains a peculiar rod-like crystalloid, the crystalloid of Lubarsch. It seems probable that the cells possessing these structures are the parent cells of the Sertoli cells. For the latter also contain crystalloids, these being of two kinds, a large one, the crystalloid of Charcot, and one or two smaller ones, similar to the Lubarsch crystalloids of the parent cells. It is supposed that both kinds of crystalloids have been formed by the division of a Lubarsch crystalloid during the growth of the Sertoli cell. This growth is very rapid, the cells increasing greatly in size, as is indi- cated in Fig. 6, and branching at their free ends to ramify around groups of sperm-ceUs, each Sertoli cell thus coming to enclose at its free end twenty-four spermatozoa, to which it acts as a nurse, supplying them with nutrition. The spermatozoa when mature are set free in the lumen of the seminiferous tubule and their Sertoli ceU then degenerates. Sertoli cells, therefore, continue to be formed throughout the period of sexual activity, new ones for each generation of spermatozoa being formed from the spermatogonia. Those ultimate spermatogonia that do not contain crystalloids are the parent cells of the spermatozoa and each divides into two cells termed primary spermatocytes, indicated in sections A and B of Fig. 6 by sc^- In the section C these cells are shown dividing to form secondary spermatocytes (sc^), and these almost imme- diately divide again, each giving rise to two spermatids (sp) which later become directly transformed into spermatozoa. From each primary spermatocyte there are formed, therefore, as the SPERMATOGENESIS IS result of two mitoses, four cells, each of which represents a spermatozoon. During these divisions important departures from the typical method of mitosis occur, these departures leading to a reduction of the chromosomes in each spermatid to one-half the number occurring in the somatic cells. The general plan by which this is Pig. 7. — Diagram Illustrating the Reduction of the Chromosomes During Spermatogenesis. 5c', Spermatocyte of the first order; sc^, spermatocyte of the second order; sp, spermatid. accomplished may be described as follows: In the division of the spermatogonia the number of chromosomes that appears is iden- tical with that found in the somatic cells, so that in a form whose somatic number is eight, eight chromosomes appear in each spermatogonium, and divide so that eight pass to each of the resulting primary spermatocytes. When these cells divide, how- l6 SPERMATOGENESIS ever, the number of chromosomes that appears is only one-half the somatic number, namely, four in the supposed case that is being described (Fig. 7, sc^). The further history of these chromosomes indicates that each is composed of four elements more or less closely united to form a tetrad, and during mitosis each tetrad divides into two dyads, four of which will therefore pass into each secondary spermatocyte. These cells (Fig. 7 , sc^) finally undergo a division in which each of the dyads they contain is halved, so that each sper- matid receives a number of single chromosomes equal to half the number characteristic for the species (Fig. 7, sp). This account of the behavior of the chromosomes during spermatogenesis assumes that all the chromosomes of the primary spermatocytes are of equal value and behave simil- arly during mitosis. It has been found, however, that in a number of forms (insects, spiders, birds, mammals, etc.) this is not the case and it seems probable that in man also certain of the spermatocytic chromosomes, termed idiochromosomes, differ decidedly from their fellows. The exact behavior of these special chromosomes is still somewhat uncertain so far as the human species is concerned, but according to the recent observations of Wieman it is as follows. In the spermatogonia! divisions twenty-four chromosomes appear, two of which are idiosomes and for convenience may be denoted as X and Y. In the primary spermatocyte only twelve chromo- somes appear, one of which is the now paired XY element, and in the metaphase this element divides longitudinally, one-half passing to each pole of the mitotic spindle (Fig. 8, XY^ and XY^) . In the secondary spermatocyte twelve chromosomes again appear and in the metaphase all divide, the X idiochromosome separating from the Y and passing to the opposite spindle pole. Each sper- matid thus contains eleven ordinary chromosomes, but in addi- tion half of them contain an X idiochromosome, while the other half contain a Y idiochromosome (Fig. 8) . Guyer and Montgomery have, however, obtaiued quite differ- ent results. According to the former the two idiochromosomes do SPERMATOGENESIS 17 not divide in the primary spermatocyte division, but pass un- changed to one pole of the spindle, so that half the secondary spermatocytes contain idiochromosomes and the other half do not. Since all the chromosomes of the secondary spermatocyte divide there will thus be two classes of spermatids, one possessing ten ordinary chromosomes and the other possessing these plus Fig. 8. — Diagram Illustrating Human Spermatogenesis. The upper figure represents a metaphase in the primary spermatocyte it which II ordinary chromosomes from the equatorial plate, the xy element having already divided the daughter elements passing to opposite poles. The middle figures repre- sent the equatorial plates of two secondary spermatocytes each consisting of 11 ordinary chromosomes and an xy element. The lower figures show the chromo- some constituents of the spermatids, each containing 11 ordmary chromosomes, but half of them with an x element and a half with a y element.— (S). The nucleus becomes the head of^^the spermatozoon, the cytoplasm surrounding it becoming reduced to an exceedingly delicate layer, so that the head is com- posed almost entirely of nuclear substance, if the head-cap be left ■THE OVUM 19 out of consideration. The spiral filament of the middle-piece is, however, formed from the cytoplasmic chondrosomes, and according to- some authors these also furnish the material for the sheath of the axial filament, though this has been denied (Meves), the sheath being regarded a differentiation of the axial filament. Each spermatozoon is, then, one of four equivalent cells, produced by two successive divisions of a primary spermatocyte and con- taining approximately one-half the number of chromosomes characteristic for the species. A BCD Pig. 9. — Stages in the Transformation of a Spermatid into a Spermatozoon. — (After Meves.) The number of spermatozoa produced during the lifetime of a single individual is very large. It has been found that i cu. mm. of human ejaculate contains 60,876 spermatozoa, a single ejaculate, therefore, containing over 200,000,000. This would indicate that during his lifetime a man may produce 340 billion spermatozoa (Lode). The Ovum.- — The human ovum is a spherical cell measuring about"o.2 mm. in diameter and is contained within a cavity situ- ated near or at the surface of the ovary and termed a Graafian follicle. This follicle is surrounded by a capsule composed of two layers, an outer one, the theca externa, consisting of fibrous tissue resembling that found in the ovarian stroma, and an inner one, the theca interna, composed of numerous spherical and fusiform cells. 20 THE OVUM Both the thecae are richly supplied with blood-vessels, the theca interna especially being the seat of a very rich capillary network.. Internal to the theca interna there is a transparent, thin, and structureless hyaline membrane, within which is the foUicle proper, whose wall is formed by a layer of cells termed the stratum granu- losum (Fig. lo, mg) which inclose a cavity filled with an albuminous fluid, the liquor folliculi. At one point, usually on the surface Pig. 10. — Sectiok through Portion of an Ovary of an Opossum (Didephys vir- giniana) showing Ova and Follicles in Various Stages of Development. b. Blood-vessel; dp, discus proligerus; mg, stratum granulosum; o, ovum; s, stroma; th, theca folliculi. nearest the center of the ovary, the stratum granulosum is greatly thickened to form a mass of cells, the discus proligerus {dp), which projects into the cavity of the folhcle and encloses the ovum {o). Usually but a single ovum is contained in any discus, though occasionally two or even three may occur. The cells of the discus proUgerus are for the most part more or less spherical or ovoid in shape and are arranged irregularly. In THE OVUM 21 the immediate vicinity of the ovum, however, they are more co- lumnar in form and are arranged in about two concentric rows, thus giving a somewhat radiated appearance to this portion of the dis- cus, which is termed the corona radiata (Fig. iz,cr). Immediately within the corona is a transparent membrane, the Zona pellucida (Fig. II, Zp), about as thick as one of the cell rows of the corona (0.02 to 0.024 mm.), and presenting a very fine radial striation Pig. II. — Ovum from Ovary of a Woman Thirty Years of Age. cr. Corona radiata; «, nucleus; p, protoplasmic zone of ovum; ps, perivitelline space; y, yolk; zp, zona pellucida. — (Nagel.) which has been held to be due to minute pores traversing the mem- brane and containing delicate prolongations of the cells of the corona radiata. Within the zona pellucida is the ovum proper, whose cytoplasm is more or less clearly differentiated into an outer more purely protoplasmic portion (Fig. 11, ^) and an inner mass (y) which contains numerous fine granules of fatty and albuminous natures. These granules represent the food yolk or deutoplasm, 22 OVULATION AND THE CORPUS LUTEUM which is usually much more abundant in the ova of other mammals and forms a mass of relatively enormous size in the ova of birds and reptiles. The nucleus («) is situated somewhat excentrically in the deutoplasmic portion of the ovum and contains a single, well-defined nucleolus. A folUcle with the structure described above and containing a fully grown ovum may measure anywhere from five to twelve millimeters in diameter, and is said to be "mature, "having reached its full development and being ready to burst and set free the ovum. This, however, is not yet mature; it is not ready for fer- tilization, but must first undergo certain changes similar to those through which the spermatocyte passes, the so-called ovum at this stage being more properly a primary oocyte. But before describing the phenorr.ena of maturation of the ovum it will be well to consider the extrusion of the ovum and changes which the follicle subsequently undergoes. Ovulation and the Corpus Luteum. — As a rule, but a single follicle near maturity is found in either the one or the other ovary at any given time. In the early stages of its develop- ment a follicle is situated somewhat deeply in the stroma of the ovary, but as the liquor foUiculi increases in amount a tension is produced within the follicle which causes it to en- large especially in the direction of least resistance, that is to- wards the surface of the ovary, where it eventually forms a marked prominence and its con- tents are separated from the ab- dominal cavity only by an exceedingly thin membrane. This membrane finally ruptures, and the liquor folliculi rushes out through the rupture, carrjang with it the ovum surrounded by some of the cells of the discus proligerus. Fig. 12. — Ovary of a Woman Nine- teen Years of Age, Eight Days after Menstruation. d. Blood-clot; /, Graafian follicle; th, theca .• — (Kallmann . ) OVULATION AND THE CORPUS LUTEUM 23 The immediate cause of the bursting of the follicle has usually been ascribed to the tension within the follicle, due to the increase of the liquor foUiculi, finally reaching the bursting point. It has been shown that the liquor foUiculi of the pig has a distinct digestive action on ovarial tissue (Schochet) and this would play an important part in both the growth and rupture of the follicle, and, furthermore, it must not be forgotten that the ovarial stroma contains a* considerable quantity of non-striped muscle tissue, a spasmodic contraction of which would produce a sudden increase of the intra-foUicular tension. Normally the ovum when expelled from its follicle is received at once into the Fallopian tube, and so makes its way to the uterus, in whose cavity it undergoes its development. Occasionally, how- ever, this normal course may be interfered with, the ovum coming to rest in the tube and there undergoing its development and producing a tubal pregnancy; or, again, the ovum may not find its way into the Fallopian tube, but may fall from the follicle into the abdominal cavity, where, if it has been fertilized, it will under- go development, producing an abdominal pregnancy; and, finally, and still more rarely, the ovum may not be expelled when the Graafian follicle ruptures and yet may be fertilized and undergo its development within the follicle, bringing about what is termed an ovarian pregnancy. All these varieties of extra-uterine preg- nancy are, of course, exceedingly serious, since in none of them is the fetus viable. With the setting free of the ovum the usefulness of the Graafian follicle is at an end, and it begins at once to undergo retrogressive changes which result primarily in the formation of a structure known as the corpus luteum (Fig. 12). On the rupture of the follicle a considerable portion of the stratum granulosum remains in place, and the cells composing it undergo proliferation and develop in their substance a yellow pigment known as lutein, the color imparted to the follicle by this substance having suggested the name, corpus luteum, that is now applied to it. The blood- vessels of the theca interna become enlarged and hernia-like pro- trusions from them penetrate between the proliferating granulosa 24 OVULATION AND THE CORPUS LUTEUM cells, carrying with them a certain amount of connective tissue. Extravasations from the capillaries into the cavity of the follicle take place during the early stages of the vascularization of the granulosa, but in time the entire cavity of the follicle becomes filled with lutein cells, separated into groups by trabeculae of connective tissue containing blood-vessels, the corpus luteum thus reaching its maturity (Fig. 13). Fig. 13. — Skction through the Corpus Luteum of a Rabbit, Seventy Hours post coitum. The cavity of the follicle is almost completely filled with lutein cells among which is a certain amount of connective tissue, g, Blood-vessels; ke, ovarial epithelium. — (Sobotta.) In later stages there is a gradual increase in the amount of con- nective tissue present and a corresponding diminution of the lutein cells, the corpus luteum gradually losing its yellow color and be- coming converted into a whitish, fibrous, scar-like body, the corpus albicans, which may eventually almost completely disappear. OVULATION AND THE CORPUS LUTEUM 2$ These various changes occur in every ruptured follicle, whether or not the ovum which was contained in it be fertilized. But the rapidity with which the various stages of retrogression ensue differs greatly according to whether pregnancy occurs or not, and it is customary to distinguish the corpora lutea which are associated with pregnancy as corpora lutea vera from those whose ova fail to be fertilized and which form corpora lutea spuria. In the latter the retrogression of the follicle is completed usually in about five or six weeks, while the corpora vera persist throughout the entire duration of the pregnancy and complete their retrogression after the birth of the child. In the account of the development of the corpus luteum given above the granulosa cells are described as being converted into the lutein cells. This is the opinion originally advanced by BischofI, but another, which was held by von Baer, was for a time more generally accepted. It maintained that the granulosa cells quickly underwent degeneration, the lutein cells and the entire mass of the corpus luteum being formed from the theca interna. The thor- ough study of the 'phenomena by Sobotta (1897) in a perfect series of mouse ovaries demonstrated that in that form the granu- losa cells persist and become converted iilto lutein cells, and later observations on other mammals, such as the rabbit (Sobotta), certain bats (Van der Stricht), the sheep (Marshall) , Spermophile (Volker, Drips), guinea-pig (Sobotta, L. Loeb) and various mar- supials (Sandes, O'Donaghue) confirmed the correctness of Sobotta's conclusions. Adverse results were obtained from the study of the human corpus luteum by Clarke and from that of the pig by Jankowski, but the more recent observations of P . Mayer (191 1) make it altogether probable that in man, also, the granulosa are the chief source of the lutein cells and^^Corner's (191 5) results lead him to believe that in the pig the granulosa cells persist and contribute to the formation of lutein. The participation of theca cells in the lutein formation is not, however, excluded, the hard and fast distinction frequently made between granulosa and thecal cells being probably unwarranted. The persistance of the corpus luteum throughout the period 26 THE RELATION OF OVULATION TO MENSTRUATION of pregnancy and its disappearance within a few weeks if preg- nancy failed to supervene, have suggested the probability of its being an organ of internal secretion directly concerned in the pro- duction of certain of the changes associated with pregnancy. It has been found that experimental removal of the corpus luteum in rabbits either before or shortly after the implantation of the ovum in the wall of the uterus produces a failure of pregnancy (Fraenkel) and similar results have been obtained in mice an(i bitches (Mar- shall and Jolly) and in Spermophiles (Drips). The cessation of ovulation which is characteristic of pregnancy has also been as- cribed to the action of the corpora lutea and there is experimental evidence in support of such a view (L. Loeb). But while the available evidence points to the existence of an internal secretion by the corpora lutea and to its having some influence in deter- mining the conditions associated with a successful pregnancy, the precise nature of its action is still obscure. The Relation of Ovulation to Menstruation. — It has long been believed that ovulation is coincident with certain periodic changes of the uterus which constitute what is termed menstrua- tion. This phenomenon makes its appearance at the time of puberty, the exact age at which it appears being determined by individual and racial peculiarities and by climate and other fac- tors, and after it has once appeared it normally recurs at definite intervals more or less closely corresponding with lunarmonths (i.e., at intervals of about twenty-eight days) imtil somewhere in the neighborhood of the fortieth or forty-fifth year, when it ceases. In each menstrual cycle four stages may be recognized, one of which, the intermenstrual, greatly exceeds the others in its duration, occupying about one-half the entire period. During this stage the mucous membrane of the uterus is practically at rest, but toward its close the membrane gradually begins to thicken and the second stage, the premenstrual stage, then supervenes. This lasts for six or seven days and is characterized by a marked proliferation and swelling of the uterine mucosa, the subjacent tissue becoming at the same time highly vascular and eventually congested. The walls of the blood-vessels situated beneath the mucosa then degen- THE RELATION OF OVULATION TO MENSTRUATION 27 erate and permit the escape of blood here and there beneath the mucous membrane, this leading to the third, or menstrual, stage in which the mucous membrane diminishes in thickness, those por- tions of it that overlie the effused blood undergoing fatty degenera- tion and desquamation, so that the stage is characterized by more or less extensive hemorrhage. The duration of this stage is from three to five days and then ensues the postmenstrual stage, lasting from four to six days, during which the mucous membrane is re- generated and again returns to the intermenstrual condition. It seems but natural to regard these changes as the expression of a periodic attempt to prepare the uterus for the reception of the fertilized ovum, this preparation being completed during the pre- menstrual stage, the succeeding menstrual and postmenstrual phenomenon being merely the return of the uterine mucosa to the resting intermenstrual stage, pregnancy not having occurred. If this be the real significance of the menstrual cycle, one would ex- pect to find ovulation occurring at a more or less definite portion of the cycle, at such a time that the ovum, if fertilized, would be able to make use of the premenstrual preparation for its reception. Since the occurence of a corpus luteum is the result of an ovula- tion and the age of the former can be determined within certain limits from its histological appearance, a comparison of the age of the corpus luteum with the condition of the uterine mucosa should indicate the period in the menstrual cycle when ovulation occurred . In other words since the development of the corpus luteum and the menstrual modifications of the uterine mucous membrane are both cylical phenomena, the question arises as to whether any correlation exists between the two and therefore between the proc- ess of ovulation and the condition of the uterine mucosa. It has been a very general belief that in the human species ovulation as a rule occurred at about the time of the menstrual flow, that is to say, just before, during, or just after the third stage of the men- strual cycle. Fraenkel, however, studied the condition of the corpus luteum in eighty-five cases in which the ovaries were re- moved in the course of operations and found that in ten, in which the operation bad been performed immediately before or 28 THE MATURATION OF THE OVUM after menstruation, no corpus luteum was present and that in twenty in which a newly formed corpus luteum was found, the last menstruation had occured on the average nineteen (13-27) days previously. The criteria adopted by Fraenkel for determining the age of the corpora lutea do not seem to have been sufficiently precise and later observers confirming his conclusion that ovula- tion corresponded with a definite stage of the menstrual cycle, referred its occurrence to a somewhat earlier period of the cycle. Thus Willemin concluded that it occurred at about fifteen days after the beginning of menstruation; Grosser, not later than six- teen days; C. Ruge II, within fourteen days; and Schroeder between fourteen and sixteen days. These numbers represent, of course, an average from which there may be considerable deviation on either side, but they indicate that ovulation in the human species corresponds on the average with the middle of. the intermenstrual period. The corpus luteum, accordingly, reaches its mature development during the premenstrual stage and may, therefore, be the determining cause of that stage (Schroeder) . In lower animals ovulation is, as a rule associated with a certain condition known as cBstrus or "heat," this being preceded by phenomena constituting what is termed promstrum and corresponding essentially to menstruation. In several forms, such as the dog, pig, horse and cow, ovulation occurs regularly in association with "heat," but in others, such as the cat, the ferret and the rabbit, it occurs at this time only if copulation also occurs. In the case of .monkeys, although the females menstruate regularly throughout the year there is nevertheless but one annual cestral period when ovulation take place (Heape). The Maturation of the Ovum — Returning now to the ovum, it has been shown that at the time of its extrusion from the Graa- fian follicle it is not equivalent to a spermatozoon but to a primary spermatocyte, and it may be remembered that such a spermatocyte becomes converted into a spermatozoon only after it has under- gone two divisions, during which there is a reduction of the number of the chromosomes to practically one-half the number characteristic for the species. THE MATURATION OF THE OVUM 29 Similar divisions and a similar reduction of the chromosomes occur in the case of the ovum, constituting what is termed its maturation. The phenomena have not as yet been observed in human ova, and, indeed, among mammals only with any approach to completeness in comparatively few forms (rat, mouse, guinea- pig, bat and cat) ; but they have been observed in so many other forms, both vertebrate and invertebrate, and present in all cases Fig. 14. — Ovum of a Mouse Showing the Maturation Spindle. The ovum is enclosed by the zona pellucida (z. p), to which the cells of corona radiata are still attached,' — (SoboUa.) the so much uniformity in their general features, that there can be little question as to their occurrence in the human ovum. In typical cases the ovum (the primary oocyte) undergoes a division in the prophases of which the chromatin aggregates to form half as many tetrads as there are chromosomes in the somatic cells (Fig. 15, oc^) and at the metaphase a dyad from each tetrad passes into each of the two cells that are formed. These two cells 30 THE MATURATION OF THE OVUM (secondary oocytes) are not, however, of the same size; one of them is almost as large as the original primary oocyte and con- tinues to be called an ovum (oc^), while the other is very small and is termed a polar globule (p). A' second division of the ovum quickly succeeds the first (Fig. 15, oc^), and each dyad gives a Fig. 15. — Diagram Illustrating the Reduction of the Chromosomes during THE Maturation of the Ovum. 0, Ovum; oc', oocyte of the first generation; oc', oocyte of the second generation; p, polar globule. single chromosome to each of the two cells which result, so that each of these cells possess half the number of chromosomes charac- teristic for the species. The second division, like the first, is unequal, one of the cells being relatively very large and constituting the mature ovum, while the other is small and is the second polar THE FERTILIZATION OF THE OVUM 31 globule. Frequently the first polar globule divides during the formation of the second one, a reduction of its dyads to single chromosomes taking place, so that as the final result of the matura- tion four cells are formed (Fig. 15), the mature ovum (o), and three polar globules (j>), each of which contains half the number of chromosomes characteristic for the species. The similarity of the maturation phenomena to those of sper- matogenesis may be perceived from the following diagram: Oocyte I {) (y\ ^cVtel"" Oocyte n O O O O ^"cVtTir OvumOO 00 00 00 Spermatids Polar globules In both processes the number of cells produced is the same and in both there is a similar reduction of the chromosomes. But while each of the four spermatids is functional, the three polar globules are non-functional, and are to be regarded as abortive ova, formed during the process of reduction of the chromosomes only to under- go degeneration. In other words, three out of every four potential ova sacrifice themselves in order that the fourth may have the bulk, that is to say, th* amount of nutritive material and cyto- plasm necessary for efficient development. The Fertilization of the Ovum. — It is perfectly clear that the reduction of the chromosomes in the germ cells cannot very long be repeated in successive generations unless a restoration of the original number takes place occasionally, and, as a matter of fact, such a restoration occurs at the very beginning of the develop- ment of each individual, being brought about by the union of a spermatozoon with an ovum. This union constitutes what is known as the fertilization of the ovum. 32 THE FERTILIZATION OF THE OVUM The fertilization of the human ovum has not been observed, but the phenomenon has been repeatedly studied in lower forms, and thorough studies of the process have been made on the mouse and the guinea-pig. The results obtained from these are taken as a basis for the following account. The maturation of the ovum is quite independent of fertiliza- tion, but in many forms the penetration of the spermatozoon into the ovum takes place before the maturation phenomena are com- pleted. This is the case with the mouse. A spermatozoon makes its way through the zona pellucida and becomes embedded in the cytoplasm of the ovum and its tail is quickly absorbed by the cyto- plasm while its nucleus and probably the middle-piece persist as distinct structures. As soon as the maturation divisions are completed the nucleus of the ovum, now termed the female pro- nucleus (Fig. 1 6, ek), migrates toward the center of the ovum, and is now destitute of an archoplasm sphere and centrosome, these structures having disappeared after the completion of the matura- tion divisions. The spermatozoon nucleus, which, after it has penetrated the ovum, is termed male pronucleus (spk), may lie at first at almost any point in the peripheral part of the cytoplasm, and it now begins to approach the female pronucleus, preceded by the middle-piece, which becomes an archoplasm sphere with its contained centrosome and is surrounded by astral rays. The two pronuclei finally come into contact near the center of the ovum, forming what is termed the segmentation nucleus (Fig. i6), the archoplasm sphere and centrosome which have been introduced with the spermatozoon undergo division, the two archoplasm spheres so formed migrate to opposite poles of the segmentation nucleus, an amphiaster forms and the compound nucleus passes through the various prophases of initosis. In describing the spermatogenesis it was shown (p: i6) that two classes of spermatozoa were formed in man, those of one class containing an X idiochromosome and the other a F element, or if Guyer's results should prove to be more correct, one class con- taining ten ordinary chromosomes plus two idiochromosomes while the other possesses only ordinary chromosomes. A similar THE FERTILIZATION OF THE OVUM 33 Fig. i6. — Six Stages in the Process of Fertilization of the Ovum of a Mouse After the first stage figured it is impossible to determine which of the two nuclei represents the male or female pronucleus, ek. Female pronucleus; rki and rki, polar globules; spk, male pronucleus. — {Sobotta.) 34 THE FERTILIZATION OF THE OVUM separation of the ova into two classes probably does not occur, all possessing an X idiochromosome or two such elements as the case may be. When, therefore, the union of the male and female pronuclei takes place in fertilization, those ova that are fertilized by a spermatozoon with a F idiochromosome will have twenty- i o + B c?- Fig. 17. — Diagrams Illustrating Sex-determination in Man, A, ON the Basis of the Spermatogenesis as Described by Wieman, B, according to Guyer's Account. four chromosomes, two of which are the X and Y idiochromosomes, while in those in which the fertilization is accomplished^ by a spermatozoon containing an X idiochromosome, there will also be twenty-four chromosomes , but two of these will be X idiochro- mosomes (Fig. IT, A). Or, according to Guyer's results, one group of ova will have twenty ordinary chromosomes plus four idiochro- THE FERTILIZATION OF THE OVUM 35 mosomes, w^ile the other will have only two idiochromosomes (Fig. 17,5). That either one or the other of these conditions occurs in the fertilization of the human ovum is merely a conjecture based on what has been shown to take place in a number of invertebrates and most clearly in insects. In these two classes of spermatozoa have been found to occur, as in man, the classes differing in some cases in the number and in others in the quality of their chromo- somes in their somatic cells, and when the spermatozoal differ- ence is one of quality in the chromosomes, the number being identical, it may be supposed that this difference also is transmitted to the adults. Further, there is strong evidence that those indi- viduals that develop from ova having the larger number of chromo- somes and that have themselves this larger number in their somatic cells are females, while those from ova with the smaller number of chromosomes and with the smaller number in their somatic cells are males; where the difference in the chromosomes is one of quality only the correlations just mentioned are not so readily perceived, though they may be presumed to exist. It would seem then that the sex of a given individual is determined by the pres- ence or absence or quality of the idiochromosomes in the fertilized ovum and is determined at the time of that fertilization. While great discrepancies occur in the various descriptions of human spermatogenesis, it seems probable that idiochromosomes occur in the human germ cells and it is justifiable to attribute to them the significance that has been so definitely shown to be attached to similar structures in insects. It seems to be a rule that but one spermatozoon penetrates the ovum. Many, of course, come into contact with it and endeavor to penetrate it, but as soon as one has been successful in its en- deavor no further penetration of others occurs. The reasons for this are in most cases obscure; experiments on the ova of inverte- brates have shown that the subjection of the ova to abnormal conditions which impair their vitality favors the penetration of more 'than a single spermatozoon {polsypermy) , and, indeed, it appears that in some forms, such as the common newt (Diemy- 36 THE FERTILIZATION OF THE OVUM ctylus), polyspermy is the rule, only one of the spermatozoa, how- ever, which have penetrated uniting with the female pronucleus, the rest being absorbed by the cytoplasm of the ovum. Fertilization marks the beginning of development, and it is therefore important that something should be known as to where and when it occurs. It seems probable that in the human species the spermatozoa usually come into contact with the ovum and fertilize it in the upper part of the Fallopian tubes, and the occur- rence of extra-uterine pregnancy (see p. 23) seems to indicate that occasionally the ovum may be fertilized even before it has been received into the tube. It is evident, then, that when fertilization is accomplished the spermatozoon must have traveled a distance of about twenty-four centimeters, the length o the upper part of the vagina being taken to be about 5 cm., that of the uterus as 7 cm., and that of the tube as 12 cm. A considerable interval of time is required for the com- pletion of this journey, even though the movement of the sperma- tozoon be tolerably rapid. The observations of Henle and Hensen indicate that a spermatozoon may progress in a straight line at about the rate of from 1.2 to 2.7. mm. per minute, while Lott finds the rate to be as high as 3.6 mm. Assuming the rate of progress to be about 2.5 mm. per minute, the time required by the spa matozoon to travel from the upper part of the vagina to the upper part of a Fallopian tube will be about one and a half hours (Strass- mann). This, however, assumes that there are no obstacles in the way of the rapid progress of the spermatozoon, which is not the case, since, in the first place, the irregularities and folds of the lining membrane of the tube render the path of the spermatozoon a labyrinthine one, and, secondly, the action of the cilia of the epithelium of the tube and uterus being from the ostium of the tube toward the os uteri, it will greatly retard the progress; furthermore, it is presumable that the rapidity of movement of the spermatozoon diminishes after a certain interval of time. It seems probable, therefore, that fertilization does not occur for some hours after coition, even providing an ovum is in the tube awaiting the approach of the spermatozoon. SUPERFETATION 37 But this condition is not necessarily present, and consequently the question of the duration of the vitality of the sperm cell be- comes of importance. Ahlfeld has found that, when kept at a proper temperature, a spermatozoon will retain its vitality outside the body for eight days, and Diihrssen reports a case in which living spermatozoa were found in a Fallopian tube removed from a patient who had last been in coitu about three and a half weeks previously. As regards the duration of the vitality of the ovum less accurate data are available. Hyrtl found an apparently normal ovum in the uterine portion of the left tube of a female who died three days after the occurrence of her second menstrua- tion, and Issmer estimates the duration of the capacity for fertili- zation of an ovum to be about sixteen days. It is evident, then, that even when the date of the coitus that led to fertilization is known, the actual moment of the latter proc- ess and, therefore, the exact age of an embryo, can only be approximated (see p. 105). For the determination of the prob- able time of parturition the date of the last menstruation is in the majority of cases the only available datum and the statistics collected by Issmer show that in 1220 cases the duration of preg- nancy averaged 280 days, counting from the first day of the last menstruation. This corresponds to ten lunar and about nine calendar months, but an estimate on this basis is only an average from which considerable variation is possible. Superfetation. — ^The occasional occurrence of twin fetuses in different stages of development has suggested the possibility of the fertilization of a second ovum as the resvSt of a coition at an appreci- able interval of time after the first ovum has started upon its devel- opment. There seems to be good reason for believing that many of the cases of supposed superfetation, as this phenomenon is termed, are instances of the simultaneous fertilization of two ova, one of which, for some cause concerned with the supply of nutrition, has later failed to develop as rapidly as the other. At the same time, however, even although the phenomenon may be of rare occurrence, it is by no means impossible, for occasionally a second Graafian follicle, either in the same or the other ovary, may be so near maturity, that its ovum is extruded soon after the first one, and if the development of the latter and the incidental changes in the uterine mucous membrane have not proceeded so far as to prevent the access of the sper- 38 LITERATURE matozoon to the ovum, its fertilization and development may ensue. The changes, however, which prevent the passage of the spermatozoon are completed early in development and the difference between the normally developed embryo and that due to superfetation will be comparatively small, and will become less and less evident as devel- opment proceeds, provided that the supply of nutrition to both embryos is equal. LITERATURE E. Ballowitz: "Untersuchungen iiber die Struktur der Spermatozoen," No. 4. Zeitschr. fiir wissensch. Zool., lit, 1891. K. VON Bardeleben: "Beitrage zur Histologic des Hodens und zur Spermatogenese beim Menschen," Archiv fiir Anat. und Physiol., Anat, Abth., Supplement, 1897. Th. Boveei: "Befruchtung," Ergebnisse der Anat. und Enfwicklungsgesch,. 1, 1892. J. G. Clark: "Ursprung, Wachsthum und Ende des Corpus luteum nach Beobach- tungen am Ovarium des Schweines und des Menschen," Archiv }iir Anat. und Physiol., Anat. Abth., 1898. G. W. Corner: "The corpus luteum of pregnancy in Swine." Conlrib. on Emhryol. ii, Carnegie Inst. PuU. 222, 1915. D. Drips: "Studies on the ovary of the Spermophile {Spermophilus cilulus tridecim- lineatus) with special reference to the corpus luteum," Amer. Jour. Anat., xxv, 1919. L. Fraenkel: "Neue Experimente zur Function des Corpus luteum," Arch, fur Gynaek., xci, 1910. L. Fraenkel: "Das zeitliche Verhalten von Ovulation und Menstruation," ZerUralbl. fiirCynaek., 1911. L. Fraenkel: "Ovulation, Konzeption und Schwangerschaftsdauer," Zeit. fiir Geburtsh. u. Gynaek., lxxiv, 1913. L. Gerlach: "Ueber die Bildung der Richtungskorper bei Mus musculus," Wies- baden, 1906. O. Grosser: "Altersbestimmung junger menschlichen Embryonen — Ovulations und Menstruationstermin,'' Anat. Anz, XLVH, 1914. S. GuTHERz: "Ueber ein bemerkenswertes Strukturelement (Heterochromosome) in der Spermiogenese des Menschen," Arch. f. mikr. Anat., Lxxix, 1912. M. F. Guyer: "Accessory Chromosomes in Man," Biol. Bull., xix, 1910. W. Heape: "The Sexual Season of Ma mm als and the Relation of the Preoestrum to Menstruation," Quart. Journ. Micros. ScL, N. S., xliv, 1901 (contains very fuU bibliography). O. Hertwig: "Vergleich der Ei- und Samenbildung bei Nematoden," Archiv fiir mikrosk. Anat.,xxxvi, 1890. F. HiTSCHMANN and L. Adler: "Der Bau der Uterusschleimhaut des geschlects- reifen Weibes, mit besonderer Beriicksichtigung der Menstruation," Monatsschr. fiir Geburtsh. und Gynaek., XXXM, igo8. J. Janowski: "Beitrag zur Entstehung des Corpus luteum der Saugetiere,'' Arch.f. mikr. Anat., Lxrv, 1904. W. B. Kirkham: "The Maturation of the Mouse Egg," Biol. Bulletin, xn, 1907. LITERATURE 39 W. B. KiEKHAM and H. S. Burr: "The breeding habits, maturation of eggs and ovulation of the albino rat," Amer. Jour. Anat., xv, 1913. H. Lams and J. Doorme: "Nouvelles recherches sur la maturation et la f&;onda- tion de I'oeuf de mammifferes," Arch, de Biol., xxiii, 1907. H. Lams: "Etude de I'oeuf de Cobaye aux premiers stades de I'embryogenese," Arch, de Biol., xxvrn, 1913. M. VON Lenhossek: "Untersuchungen fiber Spermatogenese," Archiv jiir mikrosk, Anat., LI, 1898. G. Leopold and A. Rovano; "Neuer Beitrag zur Lehre von der Menstruation und Ovulation," Arch, fiir Gynaek., Lxxxin, 1907. W. H. Longley: "The Maturation of the Egg and Ovulation in the Domestic Cat," Amer. Journ. Anat.,'xii, 1911. F. H. A. Marshall: "The CEstrus Cycle and the Formation of the Corpus luteum in the Sheep," PAJ^oJ, Trans., Ser. B, cxcvi, 1904. F. H. A. Marshall: "The Development of the Corpus luteum: a Review," Quart. Journ. Micros. Sci., N. S., xux, 1906. R. Mayer: "XJeber Corpus luteum Bildung beim Menschen," Arch, far Gynaek., xcm, 1 91 1. R. Mayer : " Ueber die Beziehung der Eizelle und des befruchteten Eies zum Follikel- apparat, sowie des Corpus luteum zum Menstruation," Arch, fiir Gynaek, c, 1913- F. Meves: "Ueber Struktur und Histogenese der Samenfaden des Meerschwein- chens," Archiv fiir mikrosk. Anat., ixv, 1899. J. W. Miller: "Corpus luteum, Menstruation und Graviditat," Arch. fUr Gynaek, CI, 1914. T. H. Montgomery: "Differentiation of the human Cells of Sertoli," Biolog. Bull, XXI, 1911. T. H. Montgomery: "Human Spermatogenesis, Spermatocytes, and Spermiogene- sis: A study in Inheritance," Jour. Acad. Nat. Sci., Phila., Ser. 1, xv, 1912. W. Nagel: "Das menschliche Ei," Archiv fUr mikrosk. Anat., xxxi, 1888. G. Niessing: "Die Betheiligung der Centralkorper und Sphare am Aufbau des Samenfadens bei Saugethieren," Archiv fUr mikrosk. Anat., XLVin, 1896. G. Retzitjs: "Die Spermien des Menschen," Biolog. Untersuch., xiv, 1909. W. Rubaschkin: "Ueber die Reifungs- und Befruchtungs-processe des Meer- schweincheneies," Anat. Hefte, xxix, 1905. C. Ruge II: "Ueber Ovulation, Corpus luteum und Menstruation," Arch, far Gynaek., c, 1913. S. S. ScHOCHEX: "A suggestion as to the process of ovulation and ovarian cyst formation," Anat. Record, x, 1916. T. Sobotta: "Die Befruchtung und Furchung des Eies der Maus," Archiv fiir mik- rosk. Anat., XLV, 1895. T. Sobotta: "Ueber die Bildung des Corpus luteum bei der Maus," Archiv fiir mikrosk. Anal., XLvn, 1897. T Sobotta: "Ueber die Bildung des Corpus luteum beim Meerschweinchen," Anat., Hefte, xxxn, 1906. J. Sobotta and G. Burckhard: "Reifung und Befruchtung der Eier des weissen Ratte," Anat. Befte, xlii, 1910. 4° LITERATURE P. Strassmann: "Beitrage zur Lehre von der Ovulation, Menstruation und Con- ception," Archiv fur Gynaekol, va, 1896. O. Van der Sxricht: "Sur le processus de I'excretion des glandes endocrines, le corps Jaune et la glande interstitielle de I'ovaire;'' Arch, de Biol, xxvii, 191 2. F. Villemin: "Le corps jaune consid6r6 comme glande a sficrfition interne," Paris, 1908. H. VON Winiwarter: "Etudes sur la spermatogenese humaine," Arch, de Biol., XXVII, 1912. W. Waldeyer: "Eierstock und Ei," Leipzig, 1870. H. L. Wieman: "The chromosomes of human spermatocytes," Amer. Journ., Anal., XXI, 191 7. CHAPTER II THE SEGMENTATION OF THE OVUM AND THE FORMATION OF THE GERM LAYERS Segmentation. — The union of the male and female pronuclei has already been described as being accompanied by the formation of a mitotic spindle which produces a division of the ovum into two cells. This first division is succeeded at more or less regular intervals by others, until a mass of cells is produced in which a differentiation eventually appears. These divisions of the ovum constitute what is termed its segmentation. The mammalian ovum has behind it a long line of evolution, and even at early stages in its development it exhibits peculiarities which can be reasonably explained only as an inheritance of past conditions. One of the most potent factors in modifying the char- acter of the segmentation of the ovum is the amount of food yolk which it contains, and it seems to be certain that the immediate ancestors of the mammalia were forms whose ova contained a con- siderable amount of yolk, many of the peculiarities resulting from its presence being still clearly indicated in the early development of the almost yolkless human ovum. To give some idea of the peculiarities which result from the presence of considerable amounts of yolk it will be well to compare the processes of segmen- tation and differentiation seen in ova with different amounts of it. A little below the scale of the vertebrates proper is a form, Amphioxus, which possesses an almost yolkless ovum, presenting a simple process of development. The fertilized ovum of Amphi- oxus in its first division separates into two similar and equal cells, and these are made four (Fig. i8, ^) by a second plane of division which cuts the previous one at right angles. A third plane at right angles to both the preceding ones brings about an eight- 41 42 THE SEGMENTATION OF THE OVTJM celled stage (Fig. i8,B), and further divisions result in the forma- tion of a large number of cells which arrange themselves in the form of a hollow sphere which is known as a blastula (Fig. i8, £). The minute amount of yolk which is present in the ovum of Amphioxus collects at an early stage of the segmentation at one pole of the ovum, the cells containing it being somewhat larger than those of the other pole (Fig. i8, B), and in the blastula the cells of one pole are larger and more richly laden with yolk than those of the other pole (Fig. i8, F). If, now, the segmenting ovum of an Amphibian be examined, it will be found that a very Fig. i8. — Stages in the Segmentation of Amphioxus. A, Four-celled stage; B, eight-celled stage; C, sixteen-celled stage; D, early blastula, E, blastula; F, section of blastula. — (Haischek.) much greater amount of yolk is present and, as in Amphioxus, it is located especially at one pole of the ovum. The first three planes of segmentation have the same relative positions as in Amphioxus (Fig. i8), but one of the tiers of cells of the eight-celled stage is very much smaller than the other (Fig. 19, B). In the subsequent stages of segmentation the small cells of the upper pole divide more rapidly than the larger ones of the lower pole, the activity of the latter seeming to be retarded by the accumula- tion of the yolk, and the resulting blastula (Fig. 19, D) shows a very decided difference in the size of the cells of the two poles. THE SEGMENTATION OF THE OVUM 43 In the ova of reptiles and birds the amount of yolk stored up in the ovum is very much greater than in the amphibia, and it is aggregated at one pole of the ovum, of which it forms the principal mass, the yolkless protoplasm appearing as a small disk upon the surface of a relatively huge mass of yolk. The inertia of this mass of nutritive material is so great that the segmentation is feonfined to the small yolkless di^fif' protoplasm and affects C D - .yiG. 19. — Stages in the Segmentation of Amblysloma. — {Eycleshymer .) consequently only a portion of the entire ovum. To distinguish this form of segmentation from that which affects the entire ovum it is termed meroblasHc segmentation, the other form being known as holohlastic. In the ovum of a turtle or a bird the first plane of segmentation crosses the protoplasmic disk, dividing it into two practically equal halves, and the second plane forms at approximately right angles to the first one, dividing the disk into four quadrants (Fig. 44 THE SEGMENTATION OF THE OVUM 20, A). The third division, like the two which precede it, is radial in position, while the fourth is circular and cuts off the inner ends of the six cells previously formed (Fig. 20, C). The disk now con- sists of six central smaller cells surrounded by six larger peripheral ones. Beyond this period no regularity can be discerned in the appearance of the segmentation planes; but radial and circular divisions continuing to form, the disk becomes divided into a Fig. 20. — Four Stages in the Segmentation of the Blastoderm of the Chick. — (Coste.) large number of cells, those at the center being much smaller than those at the periphery. In the meantime, however, the smaller central cells have begun to divide in planes parallel to the surface of the disk, which, from being a simple plate of cells, thus becomes a discoidal cell-mass. During the segmentation of the disk it has increased materially in size, extending further and further over the surface of the yolk, into the substance of which some of the lower cells of the discoidal , THE SEGMENTATION OF THE OVUM 45 cell-mass have penetrated. .A comparison of the diagram (Fig. 2i) of the ovum of a reptile at about this stage of development with the figure of the amphibian blastula (Fig. 19, D) will indicate the similarity between the two, the large yolk-mass (F) of the reptile with the scattered cells which it contains corresponding to the_ lower pole cells of the amphibian blastula, the central cavity of which is practically suppressed in the reptile. Beyond this stage, however, the similarity becomes more obscured. The peri- pheral cells of the disk continue to extend over the surface of the yolk and finally completely enclose it, forming an enveloping Fig. 21. — Diagram Illustrating a Section of the Ovum of a Reptile at a Stage Corresponding to the Blastula of an Amphibian. hi. Blastoderm; F, yolk-mass. layer which is completed at the upper pole of the egg by the dis- coidal cell-mass, or, as it is usually termed, the blastoderm. Turning now to the mammalia,* it will be found that the ovum in the great majority is almost or quite as destitute of food yolk as is the ovum of Amphioxus, with the result that the segmenta- tion is of the total or holoblastic type. It does not, however, proceed with that regularity which marks the segmentation of Amphioxus or an amphibian, but whUe at first it divides into two slightly unequal cells (Fig. 22), thereafter the divisions be- * The segmentation of the human ovum has not yet been observed; what follows is based on what occurs in the ovum of the rabbit, mole, and especially of a bat (Van Beneden). 46 THE SEGMENTATION OF THE OVUM come irregular, three-celled, four-celled, five-celled, and six-celled stages having been observed in various instances. Nor is the result of the final segmentation a hollow vesicle or blastula, but a solid mass of cells, termed a morula, is formed. This structure is not, however, comparable to the blastula of the lower forms, but Fig. 22.- -PouR Stages in the Segmentation of the Ovum of a Mouse. X. Polar globule. — iSoholta.) corresponds to a stage of reptilian development a little later than that shown in Fig. 21, since, as will be shown directly, the cells corresponding to the blastoderm and the enveloping layer are already present. There is, then, no blastula stage in the mam- malian development Differentiation now begins by the peripheral cells of the morula becoming less spherical in shape and later forming a layer of flat? tened cells, the enveloping layer, surrounding the more spherical THE SEGMENTATION OF THE OVUM 47 central cells (Fig. 23, A). In the latter vacuoles now make their appearance, especially in those cells which are nearest what may Fig. 23. — Later Stages in the Segmentation of the Ovum of a Bat. A, C, and D are sections, B a surface view. — (Van Beneden.) be regarded as the lower pole of the ovum (Fig. 22, C) and these vacuoles, gradually increasing in size, eventually become confluent. 48 TWIN DEVELOPMENT AND DOUBLE MONSTERS the condition represented in Fig. 23, D, being produced. At this stage the ovum consists of an enveloping layer, enclosing a cavity which is equivalent to the yolk-mass of the reptilian ovum, the vacuolization of the inner cells of the morula representing a belated formation of yolk. On the inner surface of the enveloping layer, at what may be termed the upper pole of the ovum, is a mass of cells projecting into the yolk-cavity and forming what is known as the inner cell-mass, a structure comparable to the blastoderm of the reptile. In one respect, however, a difference obtains, the inner cell-mass being completely enclosed within the enveloping cells, which is not the case with the blastoderm of the reptile. That portion of the enveloping layer which covers the cell-mass has been termed Rauber's covering layer, and probably owes its existence to the precocity of the formation of the enveloping layer. It is clear, then, that an explanation of the early stages of development of the mammalian ovum is to be obtained by a com- parison, not with a yolkless ovum such as that of Amphioxus, but with an ovum richly lade^ with yolk, such as the meroblastic ovum of a reptile or bird. In these forms the nutrition necessary for the growth of the embryo and for the complicated processes of development is provided for by the storing up of a quantity of yolk in the ovum, the embryo being thus independent of external sources for food. The same is true also of the lowest mammalia, the Monotremes, which are egg-laying forms producing ova resembling greatly those of a reptile. When, however, in the higher mammals the nutrition of the embryo became provided for by the attachment of the embryo to the walls of the uterus of the parent so that it could be nourished directly by the parent, the storing up of yolk in the ovum was unnecessary and it became a holoblastic ovum, although many peculiarities dependent on the original meroblastic condition persisted in its development. Twin Development.^ — -As a rule, in the human species but one embryo develops at a time, but the occurrence of twins is by no means infrequent, and triplets and even quadruplets occasinoally are developed. The occurrence of twins may be due to two causes, either to the simultaneous ripening and fertilization of two ova, either from one or from both ovaries, or to the separation of a single fertilized TWIN DEVELOPMENT AND DOXJBLE MONSTERS 49 ovum into two independent parts during the early stages of develop- ment. That twins may be produced by this latter process has been abundantly shown by experimentation upon developing ova of lower forms, each of the two cells of an Amphioxus ovum in that stage of development, if mechanically separated, completing its development and producing an embryo of about half the normal size. Furthermore, it has been shown (Patterson) that in the armadillo a division of the embryonic anlage into four parts at an early stage of the develop- ment is a normal process, the four young produced at a birth being quadruplets produced from a single ovum. It is noteworthy that in the case of the armadillo the four indi- viduals of each birth are of the same sex, and it is probable that human twins of the same sex and closely similar in appearance, what are termed "like" twins, are the result of a division of a single embryonic anlage, while "unlike" twins are produced by the simultaneous fer- tilization of two separate ova. Double Monsters and the Duplication of Parts. — The occasional occurrence of double monsters is explained by an imperfect separation into two parts of an originally single embryo, the extent of the separa- tion, and probably also the stage of development at which it occurs, determining the amount of fusion of the two individuals constituting the monster. All gradations of separation occur, from almost coftiplete separation, as seen in such cases as the Siamese twins, to forms in which the two individuals are unite throughout the entire length of their bodies. The separation may also affect only a portion of the embryo, producing, for instance, double-faced or double-headed mon- sters or various forms of so-called parasitic monsters; and finally, it may affect only a group of cells destined to from a special organ, producing an excess of parts, such as supernumerary digits or accessory spleens. It has been observed in the case of double monsters that one of the two fused individuals always has the position of its, various organs reversed, it being, as it were, the looking-glass image of its fellow. Cases of a similar situs inversus viscerum, as it is called, have not in- frequently been observed in single individuals, and a plausible ex- planation of such cases regards them as one of a pair of twins formed by the incomplete division of a single embryo, the other individual having ceased to develop and either having undergone degeneration or having been included within the body of the^ apparently single indivi- dual. Another explanation of situs inversus has been advanced (Con- klin) on the *basis of what has been observed in certain invertebrates. In some species of snails situs inversus is a noimal condition and it has been found that the inversion may be traced back in the development even to the earliest segmentation stages. The conclusion is thereby indicated that its primary cause may reside in an inversion of the polarity of the ovum, evidence being forthcoming in favor of the view that even in the ovum of these and other forms there is probably a so FORMATION OF THE GERM LAYERS distinct polar differentiation. How far this view may be applicable to the mammalian ovum is uncertain, but if it be applicable it explains the phenomenon of inversion without complicating it with the question of twin-formation. The Formation of the Germ Layers. — During the stages which have been described as belonging to the segmentation period of development there has been but little differentiation of the cells. In Amphioxus and the amphibians the cells at one pole of the blastula are larger and more yolk-laden than those at the other pole, and in the mammals an inner cell-mass can be distinguished from the enveloping cells, this latter differentiation having been km .r'^^J?' '.->*-> . yi ,^._- ; ^ J,'*'.> w ^»s* vfi t^fitl »Vj J^P i^ f ^ A B Fig. 24. — Two Stages in the Gastrulation of Amphioxus. — (Morgan and Hazen.) anticipated in the reptiles and being a differentiation of a portion of the ovum, from which alone the embryo will develop, from a portion which will give rise to accessory structures. In later stages a differentiation of the inner cell-mass occurs, resulting first of all in the formation of a two-layered or diploblastic and later of a three-layered or triplohlastic stage. Just as the segmentation has been shown to be profoundly modified by the amount of yolk present in the ovum and by its secondary reduction, so, too, the formation of the three primitive layers is much modified by the same cause, and to get a clear understanding of the formation of the triploblastic condition of the mammal it will be necessary to describe briefly its develop- ment in lower forms. FORMATION OF THE GERM LAYERS Si In Amphioxus the diploblastic condition results from the flat- tening of the large-celled pole of the blastula (Fig. 24, A), and finally from the invagination of this portion of the vesicle within the other portion (Fig. 24, B). The original single- walled blastula in this way becomes converted into a double-walled sac termed a gastrula, the outer layer of which is known as the ectoderm or epiblast and the inner layer as the endoderm or hypoblast. The cavity bounded by the endoderm is the primitive gut or archen- teron, and the opening by which this communicates with the ex- terior is the blastopore. This last , , , ,- ^ structure is at first a very wide /^^^^T^^^ix opening, but as development pro- M^v^ri^rw^^M^K ceeds it becomes smaller, and „t, '^^ Vj^ ^yffMlHPP^ finally is a relatively small open- ^H^m^^^^^m^^i ing situated at the posterior ex- ^^^^ ^^H tremity of what will be the dorsal '^"'^^H- — ^M|~J surface of the embryo. V^^fe?»»^ ^^^^^^ As the oval embryo continues ^^^^°/'Tf^W\\^^y'"'^ to elongate in its later develop- ^^°^tfef>R5>^ ment the third layer or mesoderm p^^ .^.-transverse Section of makes its appearance. It arises Amphioxus Embryo with Five ,, irii/ .\ r ,1 T 1 Mesodermic Pouches. as a lateral fold (mp) of the dorsal ^^^ Notochord; d. digestive cavity; surface of the endoderm {en) on «c, ectoderm; e«, endoderm; m.medul- , . , . ,, • 1 11 1- • lary plate; mp, mesodermic pouch. — each side of the middle line as m- (Hatschek.) dicated in the transverse section shown in Fig. 25. This fold eventually becomes completely con- stricted off from the endoderm and forms a hollow plate oc- cupying the space between the ectoderm and endoderm, the cavity which it contains being the body-cavity or ccelom. In the amphibia, where the amount of yolk is very much greater than in Amphioxus, the gastrula tion becomes considerably modi- fied. On the line where the large- and small-celled portions of the blastula become continuous a crescentic groove appears and, deepening, forms an invagination (Fig. 26, gc), the roof of which is composed of relatively small yolk-containing cells while its floor is formed by the large cells of the lower pole of the blastula. The 52 FORMATION OF THE GERM LAYERS cavity of the blastula is not sufficiently large to allow of the typical invagination of all these large cells, so that they become enclosed by the rapid growth of the ectoderm cells of the upper pole of the ovum over them. Before this growth takes place the blastopore corresponds to the entire area occupied by the large yolk cells, but later, as the growth of the smaller cells gradually encloses the larger ones, it becomes smaller and is finally represented by a Fig. 26. — Section through a Gastrula of AmUystoma. dl. Dorsal lip of blastopore; gc, digestive cavity; gr, area of mesoderm formation; mes, mesoderm. — (Eydeskymer.) small opening situated at what w'll be the hind end of the embryo. Soon after the archenteron has been formed a solid plate of cells, eventually splitting into two layers, arises from its roof on each side of the median line and grows out into the space between the ectoderm and endoderm (Fig. 27, mk^ and mk'^), evidently corresponding to the hollow plates formed in the same situations in Amphioxus. This is not, however, the only source of the mesoderm in the amphibia, for while the blastopore is still quite large there may be found surrounding it, between the endoderm and ectoderm, a ring of mesodermal tissue (Fig. 26, tnes). As the FORMATION OF THE GERM LAYERS S3 blastopore diminishes in size and its lips come together and unite, the ring of mesoderm forms first an oval and then a band lying beneath the line of closure of the blastopore and united with both the superjacent ectoderm and the subjacent endoderm. This line of fusion of the three germ layers is known as the primitive streak. It is convenient to distinguish the mesoderm of the primitive streak from that formed from the dorsal wall of the archenteron by speaking of the former as the prostomial and the latter as the gastral mesoderm, though it must be understood that V Fig. 27. — Section through an Embryo Amphibian (Triton) of 2j^ Days, show- ing THE Formation of the Gastral Mesoderm. ak. Ectoderm; ch, chorda endoderm; dk, digestive cavity; ik, endoderm; mfe' and mk'', somatic and splanchnic layers of the mesoderm. D, dorsal and V, ventral. — {Hertwig.) the two are continuous immediately in front of the definitive blastopore. In the reptiha still greater modifications are found in the method of formation of the germ layers. Before the enveloping cells have completely surrounded the yolk-mass, a crescentic groove, resembling that occurring in amphibia, appears near the posterior edge of the blastoderm the cells of which, in front of the groove, arrange themselves in a superficial layer one cell thick, which may be regarded as the ectoderm (Fig. 28, ec), arid a subjacent mass of somewhat scattered cells. Later the lowermost cells of this sub- jacent mass arrange themselves in a continuous layer, constituting 54 FORMATION OF THE GERM LAYERS what is termed the primary endoderm (en^), while the remaining cells, aggregated especially in the region of the crescentic groove, form the prostomial mesoderm (prm). In the region enclosed by the groove a distinct delimitation of the various layers does not occur, and this region forms the primitive streak. The groove now begins to deepen, forming an invagination of secondary en- doderm, the extent of this invagination being, however, very different in different species. In the gecko (Will) it pushes for- PiG. 28. — Longitudinal Sections through Blastoderms of the Gecko, showing ' Gastrulation. ec. Ectoderm; en, secondary endoderm; en', primary endoderm; prm, prostomial mesoderm. — (Will.) ward between the ectoderm and primary endoderm almost to the anterior edge of the blastoderm (Fig. 28, B), but later the cells forming its floor, together with those of the primary endoderm immediately below, undergo a degeneration, the roof ceUs at the tip and lateral margins of the invagination becoming continuous with the persisting portions of the primary endoderm (Figs. 28, C and 29, B). This layer, following the enveloping cells in their growth over the yolk-mass, gradually surrounds that structure so FORMATION OF THE GERM LAYERS 55 that it comes to lie within the archenteron. In some turtles, on the other hand, the disappearance of the floor of the invagination takes place at a very early stage of the infolding, the roof cells only persisting to grow forward to form the dorsal wall of the arch- enteron. This interesting abbreviation of the process occurring in the gecko indicates the mode of development which is found in the mammalia. , The existence of a prostomial mesoderm in connection with the primitive streak has already been noted, and when the invagina- tion takes place it is carried forward as a narrow band of cells on Fig. 29. — Diagrams Illustrating the Formation of the Gastral Mesoderm IN THE Gecko. e. Chorda endoderm; ec, ectoderm; en, secondary endoderm; ««,' primary endoderm gm, gastral mesoderm. — (Will.) each side of the sac of secondary endoderm. After the absorption oi the ventral wall of the invagination a folding or turning in of the margins of the secondary endoderm occurs (Fig. 29), whereby its lumen becomes reduced in size and it passes off on each side into a double plate of cells which constitute the gastral mesoderm. Later these plates separate from the archenteron as in the lower forms. All the prostomial mesoderm does not, however, arise from the primitive streak region, but a considerable amount also S6 FORMATION OF THE GERM LAYERS has its origin from the ectoderm covering the yoke outside the lim- its of the blastoderm proper, a mode of origin which serves to ex- plain the phenomena later to be described for the mammalia. Fig. 30. — Sections of Ova of a Bat Showing (A) the Formation of the Endo- DERM AND (B AND C) OF THE AMNIOTIC Cavity. — {Van Beneden.) In comparison with the amphibians and Amphioxus, the rep- tilia present a subordination of the process of invagination in the formation of the endoderm, a primary endoderm making its appear- FORMATION OF THE GERM LAYERS 57 ance independently of an invagination, and, in association with this subordination, there is an early appearance of the primitive streak, which, from analogy with what occurs in the amphibia, may be assumed to represent a portion of the blastopore which is closed from the very beginning. Turning now to the mammalia, it will be found that these peculiarities become still more emphasized. The inner cell-mass of these forms corresponds to the blastoderm of the reptilian ovum, and the first differentiation which appears in it concerns the cells situated next the cavity of the vesicle, these cells differentiat- ing to form a distinct layer which gradually extends so as to form a complete lining to the inner surface of the enveloping cells (Fig. 30, A ) . The layer so formed is endodermal and corresponds to the pri- mary endoderm of the reptiles. Before the extension of the endoderm is completed, however, cavities begin to appear in the cells constituting the remainder of the inner mass, especially in those immediately beneath Rauber's cells (Fig. 30, .B), and these cavities in time coalesce to form a single large cavity bounded above by cells of the enveloping layer and below by a thick plate of cells, the embryonic disk (Fig. 29, C). The cavity so formed is the amniotic cavity, whose further history will be considered in a subsequent chapter. It may be stated that this cavity varies greatly in its development in different mammals, being entirely absent in the rabbit at this stage of development and reaching an excessive development in such forms as the rat, mouse, and guinea-pig. The condition here described is that which occurs in the bat and the mole, and it seems probable, from what occurs in the youngest human embryos hitherto observed, that the processes in man are closely similar. While these changes have been taking place a splitting of the enveloping layer has occurred (Fig. 30, C), it becoming divided into an outer layer whose cells unite to form a syncytium, and an inner one in which the cell boundaries remain distinct. The two layers together form what is termed the trophoblast, from the part it subsequently plays in the nutrition of the embryo, the outer layer being the plasmodi-trophohlast and the inner the cyto- 58 FORMATION OF THE GERM LAYERS trophoblast. In the bat of whose ovum Fig. 30 C, represents a section, that portion of the cyto-trophoblast which forms the roof of the amniotic cavity disappears, only the plasmodi-tropho- blast persisting in this region, but in another form this is not the case, the roof of the cavity being composed of both layers of the trophoblast. A rabbit's ovum in which there is yet no amniotic cavity and no splitting of the enveloping layer shows, when viewed from above, Fig. 31. — A, Side View of Ovum of Rabbit Seven Days Old (KolUker); Bi Embryonic Disk of a Mole (Heape); C, Embryonic Disk of a Dog's Ovum of ABOUT Fifteen Days (Bonnet). ed, Embryonic disk; hn, Hensen's node; mg, medullary groove; ps, primitive streak; va, vascular area. a relatively small dark area on the surface, which is the embryonic disk. But if it be looked at from the side (Fig. 31, A), it will be seen that the upper half of the ovum, that half in which the em- bryonic diski occurs, is somewhat darker than the lower half, the line of separation of the two shades corresponding with the edge of the primary endoderm which has entended so far in its growth around the inner surface of the enveloping layer. A little later a dark area appears at one end of the embryonic disk, produced by FORMATION OF THE GERM LAYERS 59 a proliferation of cells in this region and having a somewhat cres- centic form. As the embryonic disk increases in size a longitudinal band makes its appearance, extending forward in the median line nearly to the center of the disk, and represents the primitive streak (Fig. 31, B), a slight groove along its median line forming what is termed the primitive groove. In slightly later stages an especially dark spot may be seen at the front end of the primitive streak and is termed Hensen's node (Fig. 31, C, hn), while still later a dark streak may be observed extending forward from this in the median line and is termed the head process of the primitive' streak. Fig. 32. — Posterior Portion of a Longitudinal Section through the Em- bryonic Disk of a Mole. bl. Blastopore, ec, ectoderm; en, endoderm; prm, prostomial mesoderm. — {After Heape.) To understand the meaning of these various dark areas re- course must be had to the study of sections. A longitudinal section through the embryon^'c d'sk of a mole ovum at the time when the crescentic area makes its appearance is shown in Fig. 32. Here there is to be seen near the hinder edge of the disk what is potentially an opening (bl) , in front of which the ectoderm (ec) and primary endoderm (en) can be clearly distinguished, while behind it no such distinction of the two layers is visible. This stage may be regarded as comparable to a stage immediately preceding the invagination stage of the reptilian ovum, and the region behind the blastopore will correspond to the reptilian primitive streak. The later forward extension of the primitive streak is due to the mode of growth of the embryonic disk. Between the stages repre- sented in Figs. 32 and 31, B, the disk has enlarged considerably and the primitive streak has shared in its elongation. Since the blastopore of the eai-lier stage is situated immediately in front of 6o FORMATION OF THE GERM LAYERS the anterior extremity of the primitive streak, the point corres- ponding to it in the older disk is occupied by Hensen's node, this structure, therefore, representing a proliferation of cells from the region formerly occupied by the blastopore. As regards the head process, it is at first a solid cord of cells Pig. 33. — Transverse Section of the Embryonic Area of a Dog's Ovum at ABOUT the Stage of Development shown in Fig. 3o,C. The section passes'through the head process {Chp) ;^M, mesoderm. — {Bonnet.) which grows forward in the median line from Hensen's node, lying between the ectoderm and the primary endoderm. Later a lumen appears in the center of the cord, forming what has been termed the chorda canal, and, in some forms, including man, the canal Fig. 34. — Diagram of a Longitudinal Section through the Embryonic Disk of A Mole. am, Amnion; ce, chorda endoderm; ec, ectoderm; nc, neurenteric canal; ps, primitive streak. — (,Heape.) opens to the surface at the center of Hensen's node. The cord then fuses with the subjacent primary endoderm and then opens out along the line of fusion, becoming thus transformed into a flat plate of cells continuous at either side with the primary endo- derm (Fig. 33, Chp). The portion of the chorda canal which FORMATION OF THE GERM LAYERS 6 1 traverses Hensen's node now opens below into what will be the primitive digestive tract and is termed the neurenteric canal (Fig. 34, nc) ; it eventually closes completely, being merely a transitory structure. The similarity of the head process to the invagination which in the reptilia forms the secondary endoderm seems clear, the only essential difference being that in the mammalia the head process arises as a solid cord which subsequently becomes hollow, instead of as an actual invagination. The difference accounts for the occurrence of Hensen's node and also for the mode of forma- tion of the neurenteric canal, and cannot be considered as of great moment since the development of what are eventually tubular ff/n^ Fig. 35. — Transverse Section through the Embryonic Disk of a Rabbit. ch. Chorda endoderm; ee, ectoderm; en, endoderm; gm, gastral mesoderm. — {After van Beneden.) structures {e.g., glands) as solid cords of cells which subsequently hollow out is of common occurrence in the mammalia. It should be stated that in some mammals apparently the most anterior portion of the roof of the archenteron is formed directly from the cells of the primary endoderm, which in this region are not re- placed by the head process, but aggregate to form a compact plate of cells with which the anterior extremity of the head process unites. Such a condition would represent a further modification of the original condition. As regards the formation of the embryonic mesoderm it is not always possible to recognize both the prostomial and gastral mesoderm in the mammalian ovum. A mass of pros- tomial mesoderm is formed from the primitive streak and as the head process grows forward a band of this mesoderm extends for- ward on either side of it, but whether contributions are added to 62 FORMATION OF THE GERM LAYERS these bands from the head process is uncertain. Later on the medial margins of the bands come into intimate relation with the head process or chorda endoderm, just where this unites with the primitive endoderm, and an appearance may be presented closely similar to that shown in reptilia (compare Fig. 29, D and Fig. 35). If, in the mammalia the head process tissue takes no part in the formation of these lateral plates of mesoderm it may be supposed that a concentration of the development has taken place, the ABC D Pig. 36. — Diagrams Illustrating the Relations of the Chick Embryo to the Primitive Streak at Different Stages of Development. — (Peebles.) head process being composed purely of chorda endoderm, while the mesoderm associated with this in the reptilia now takes its origin directly from the primitive streak. The lateral plates of mesoderm are at first solid (Fig. 35, gm), but their cells early ar- range themselves in two layers, between which a space, termed the body-cavity or ccelom, later appears. In addition to this, embryonic mesoderm a certain amount, sometimes quite large, of the same layer is found lining the inner surface of the cytotrophoblast, lying between this and the primary SIGNIFICANCE OF THE GERM LAYERS 63 endoderm. The exact source of this extra-embryonic mesoderm is uncertain, though it seems probable that it is formed in situ, and is perhaps represented in the reptilian ovum by the cells which underlie the ectoderm in the regions peripheral to the blastoderm proper (see page 55). It has been experimentally determined (Assheton, Peebles) that in the chick, whose embryonic disk presents many features similar to those of the mammalian ovum, the central point of the unincubated disk corresponds to the anterior end of the primitive streak and to the point situated immediately behind the heart of the later embryo and immediately in front of the first mesodermic somite (see p. 79), as shown in Fig. 36. If these results be regarded as applicable to the human embryo, then it may be supposed that in this the head region is developed from the portion of the embryonic disk situated in front of Hensen's node, while the entire trunk is a product of the region occupied by the node. The Significance of the Germ Layers. — The formation of the three germ layers is a process of fundamental importance, since it is a differentiation of the cell units of the ovum into tissues which have definite tasks to fulfil. As has been seen, the first stage in the development of the layers is the formation of the ectoderm and endoderm, or, if the physiological nature of the layers be considered, it is the differentiation of a layer, the endoderm, which has princi- pally nutritive functions. In certain of the lower invertebrates, the class Ccelentera, the differentiation does not proceed beyond this diploblastic stage, but in all higher forms the intermediate layer is also developed, and with its appearance a further division of the functions of the organism supervenes, the ectoderm, situated upon the outside of the body, assuming the relational functions, the endoderm becoming still more exclusively nutritive, wh'le the remaining functions, supportive, excretory, locomotor, reproduc- tive, etc. are assumed by the mesoderm. The manifold adaptations of development obscure in certain cases the fundamental relations of the three layers, certain por- tions of the mesoderm, for instance, failing to differentiate simul- taneously with the rest of the layer and appearing therefore to be a portion of either the ectoderm or endoderm. But, as a rule, the 64 SIGNIFICANCE OF THE GERM LAYERS layers are structural units of a higher order than the cells, and since each assumes definite physiological functions, definite structures have their origin from each. Thus from the ectoderm there develop: 1. The epidermis and its appendages, hairs, nails, epidermal glands, and the enamel of the teeth. 2. The epithelium lining the mouth and the nasal cavities, as well as that lining the lower part of the rectum. 3. The nervous system and the nervous elements of the sense- organs, together with the lens of the eye. iFrom the endoderm develop: 1 . The epithelium lining the digestive tract in general, together with that of the various glands associated with it, such as the liver and pancreas. 2. The lining epithelium of the larynx, trachea, and lungs. 3. The epithelium of the bladder and urethra (in part). From the mesoderm there are formed : 1. The various connective tissues, including bone and the teeth (except the enamel) . 2. The muscles, both striated and non-striated. 3. The circulatory system, including the blood itself and the lymphatic system. 4. The lining membrane of the serous cavities of the body. 5. The kidneys and ureters. 6. The internal organs of reproduction. From this list it will be seen that the products of the mesoderm are more varied than those of either of the other layers. Among its products are organs in which in either the embryonic or adult condition the cells are arranged in a definite layer, while in other structures its cells are scattered in a matrix of non-cellular ma- terial, as, for example, in the connective tissue, bone, cartilage, and the blood and lymph. It has been proposed to distinguish these two forms of mesoderm as mesothelium and mesenchyme respectively , a distinction which is undoubtedly convenient, though probably devoid of the fundamental importance which has been attributed to it by some embryologists. LITERATURE 65 LITERATURE R. Assheton: "The Reinvestigation into the Early Stages of the Development of the Rabbit," Quarterly Journ. of Microsc. Science, xxxvn, 1894. R. Assheton: "The Development of the Pig During the First Ten Days," Quarterly Journ. of Micros. Science, XLI, 1898. R. Assheton: "The Segmentation of the Ovum of the Sheep, with Observations on the Hypothesis of a Hypoblastic Origin for the Trophoblast," Quarterly Journ. cf Microsc. Science,XLi, 1898. E. VAN Beneden : " Recherches sur I'embryologie des Mammiferes. De la segmenta- tion, de la formation de la cavit6 blastodermique et de I'embryon didermique chez le Murin," Arch, de Biol., xxvi, 1911. E. VAN Beneden: "Recherches sur Tembryologie des Mammiferes II: De la ligne primitive, du prolongement cephalique, de la notochorde et du mesoblaste chez le lapin et chez le murin," Arch, de Biol., xxvii, 1912. R. Bonnet: "Beitrage zur Embryologie der Wiederkauer gewonnen am Schafei," Archiv filr Anat. und Physiol., Anat. Abth., 1884 and 1889. R. Bonnet: "Beitrage zur Embryologie des Hundes," Anal. Hefte, DC, 1897. G. Born: "Erste Entwickelungsvorgange," Ergebnisse der Anat. und Entwicklungs- gesch., I, 1892. E. G. Conklin: "The Cause of Inverse Symmetry," Anatom. Anzeiger, xxni, 1903. A. C. Eycleshymer: "The Early Development of Amblystoma with Observations on Some Other Vertebrates," Jour, of Morphol., x, 1895. B. Hatschek: "Studien fiber Entwicklung des Amphioxus," Arbeilen aus dem zoolog. Instil, zu Wien, iv, 1881. W. Heape: "The Development of the Mole (Talpa europsea)," Quarterly Journ. of Micros. Science, xxin, 1883. G. C. HtTBEE: "On the Anlage and Morphogenesis of the Chorda dorsalis in Mam- malia, in particular the Guinea-pig (Cavia Cobaya)". Anat. Record xiv, 1918. A. A. W. Hubrecht: "Studies on Mammalian Embryology II: The Development of the Germinal Layers of Sorex vulgaris," Quarterly Journ. of Microsc. Science, XXXI, 1890. F. Keibel: "Studien zur Entwicklungsgeschichte des Schweines," Morpholog. Arbeiten, iii, 1893. F. Keibel: "Die Gastrulation unli die Keimblattbildung der Wirbeltiere," Ergeb- nisse der Anat. und Entwicklungsgesch., x, 1901. M. KunsemCller: "Die Eifurchung des Igels (Erinaceus emopxus L.), " Zeitschr. fiir wissensch. Zool., lxxxv, 1906. K. Mitsukuri and C. Ishikawa: "On the Formation of the Germinal Layers in Chelonia," Quarterly Journ. of Microsc. Science, xxvii, 1887. F. Peebles: "The Location of the Chick Embryo upon the Blastoderm," Journ. of Exper. Zool., i, 1904. E. Selenka: "Studien fiber Entwickelungsgeschichte der Thiere," 4tes Heft, 1886- 87; stes Heft, 1891-91. J. Sobotta: "Die Befruchtung und Furchung des Eies der Maus," Archiv fur mik- rosk. Anat., XLV, 1895. 5 66 LIIERATURE J. Sobotta: "Die Furchung des Wirbelthiereies." Ergebnisse der Anal. und Entmcke- lungsgeschichie, vi, 1897. J. Sobotta: "Neuere Anschauungen viber Entstehung der Doppel (miss) bild- ungen, mit besonderer Berucksichtigung der menschlichen Zwillingsgeburten," Wiirzburger Ahhandl., i, 1901. H. H. Wilder: "Duplicate Twins and Double Monsters," Amer. Jour, of Anat., iii, 1904. L. Will: "Beitrage zur Entwicklungsgeschichte der Reptilien," Zoolog. JahrlUcher Abth. fiir Anal., vi, 1893. CHAPTER III THE MEDULLARY GROOVE, NOTOCHORD, AND MESO- DERMIC SOMITES In the preceding chapter the development of the mammalian ovum has been described up to and including the formation of the three germinal layers. The earlier stages of development there described are practically unknown in the human ovum, but for the stages subsequent to the establishment of the germinal layers human material is available, and it will, therefore, now be con- venient to consider the structure of the younger human ova at present known and to trace in them the appearance and develop- ment of such structures as the primitive streak, the head process and the gastral mesoderm. The youngest human ovum at present known is that described by Bryce and Teacher, but, unfortunately, it presents certain features that are evidently abnormal, so that it becomes doubtful how far it may be accepted as representing the typical condition . The trophoblast, which was very thick and clearly differentiated into two layers, enclosed a space whose diameter was about 0.63 mm. and which was largely occupied by a loose syncytial tissue. Toward the center of this was an irregular cavity in which were two vesicles, quite separate from one another and probably together representing the embryo, the smaller one being the amniotic cavity and the larger one the cavity lined by the endoderm and known as the yolk-sac (Fig. 37). The separation of these two structures is apparently an abnormality and it is possible that the cavity in which they lie is, as Bryce and Teacher suggest, an artefact pro- duced by contraction of the syncytial tissue during the preserva- tion of the ovum. If comparison of this ovum with those of other mammals is warranted, it may be likened to that of the bat as shown in Fig. 67 68 THE MEDULLARY GROOVE 30, C, with the difference that the space between the primary endo- derm and the trophoblast is greatly enlarged in the human ovum and is occupied by loose syncytial tissue, which may be termed the cellular magma. This condition may be represented diagrammat- ically as in Fig. 39, A , in which the magma is represented as some- what condensed around the amniotic cavity and yolk-sac and upon the inner surface of the trophoblast. Whence this magma tissue Pig. 37.- -Prom a Reconstruction of the Bryce- Teacher Ovum. — 'Bryce-Teacher.) is derived is as yet uncertain, but it seems probable that it repre- sents a precocious development of the extra-embryonic mesoblast, i.e., of that portion of the mesoblast that lies outside the actual limits of the embryonic rudiment (see page 62). Somewhat older are the ova described by Peters, Fetzer, Jung, Linzenmeier and Herzog. The Peters ovum was taken from the uterus of a woman who had committed suicide one calendar month after the last menstruation, and it measured about i mm. in diameter. The entire inner surface of the trophoblast (Fig. 38 ce) was lined by a layer of mesoderm (cm), whic6, on the surface furthest away from the uterine cavity, was considerably thicker THE MEDULLARY GROOVE 69 than elsewhere, forming an area of attachment of the embryo to the wall of the ovum. In the substance of this thickening was the amniotic cavity (am), whose roof was formed by flattened cells, which, at the sides, became continuous with a layer of columnar cells forming the floor of the cavity and constituting the embryonic ectoderm (ec) . Immediately below this was a layer of mesoderm (m) which split at the edge of the embryonic disk into two layers, one of which became continuous with the mesodermic thickening Fig 38. — Section of Embryo and Adjacent Portion of an Ovum of i mm. am. Amniotic cavity; ce, chorionic ectoderm; cm, chorionic mesoderm; ec, embryonic ectoderm; en, endoderm; m, embryonic mesoderm; ys, yolk-sac. — (Peters.) and so with the layer of mesoderm lining the interior of the tropho- blast, while the other enclosed a sac lined by a layer of endodermal cells and forming the yolk-sac ,(3'^)- The total length of the embryo was 0.19 mm., and so far as its ectoderm and mesoderm are concerned it might be described as a flat disk resting on the surface of the yolk-sac, though it must be understood that the yolk-sac also to a certain extent forms part of the embryo. This embryo seems to be in an early stage of the primitive streak formation, before the development of the head process. On 70 THE MEDULLARY GROOVE comparing it with the stage of development represented in Fig. 39, A, it will be seen to present some important advances. The cavity (Fig. 39, B, C,) into which the yolk-sac projects is unrepre- sented in Fig. 39, ^ , and seems to have been formed by the concen- tration of the cells of the cellular magma upon the trophoblast and around the yolk-sac and amniotic cavity. The cavity is oc- cupied by a mucous fluid, destitute of cellular elements at this stage and forming what is termed the reticular magma, and the size of the human ovum at this stage and later is mainly due to the rapid growth of this cavity. The fact that the cavity is every- Pi-~. Fig. 39. — Diagrams to show the Probable Relationships ot the Parts in the Embryos Represented in Figs. 37 and 38 ac. Amniotic cavity; c, extra-embryonic coelom; Co, embryonic ccelom; Cy, cyto-tro- phoblast; m, cellular magma; me, chorionic mesoderm; PI, plasmodi-trophoblast; y, yolk sac. where bounded by mesoderm suggests that it is the extra-em- bryonic body-cavity, formed precociously before the splitting of the embryonic mesoderm (see p. 62). It seems more probable, however, that the extra-embryonic coelom is really represented by certain cavities lined with a flattened epithelium which occur in the immediate neighborhood of the embryo (Figs. 38 and 39, B, Co). These, in later stages, probably become continuous with the cavity occupied by the reticular magma by the breaking down of the separating walls, and if this be the correct interpretation of the THE MEDULLARY GROOVE 71 facts the extra-embryonic coelom is formed precociously in the human ovum and the cavity occupied by the reticular magma eventually becomes part of it. From this stage onward the tro- phoblast and the layer of mesoderm lining it may together be \ /-^-Ta. Fig. 40. — The Embryo v. H. of von Spep;. The Left Half of the Chorion has BEEN Removed to show the Embryo. u, Amniotic cavity; h, belly-stalk; ch, chorion; d, yolk-sac; e. extra-embryonic coelom; k, embryonic disk; s. chorionic villus. — [von Spee.) spoken of as the chorion, the mesoderm layer being termedjthe chorionic mesoderm. A little older again than the Peters and Herzog ova are those described by Strahl and Beneke, and by von Spee (embryo v. H.), the chorionic cavity of the former two having an average diameter Fig. 41. — Embryo from the Beneke Ovum, the Roof of the Amniotic Cavity HAVING been Removed. From a model, b. Belly-stalk; p.g., primitive groove; y, yolk-sac. — (Strahl and Beneke.) of about 2.4 mm., while the corresponding size of the latter two was somewhat less than 4.0 mm. Notwithstanding the considerable increase in the size of these older ova, due to the continued increase in the size of the extra-embryonic coelom, the embryos are but 72 THE MEDULLARY GROOVE little advanced beyond the stage shown by the Peters embryo. The thickening of the chorionic mesoderm that encloses the amni- otic cavity has now become smaller relatively to the extent of the chorion and forms a pedicle, known as the belly-stalk (Fig._4o, b. at the extremity of which is the yolk-sac (d). Furthermore, the amniotic cavity (a) now lies somewhat eccentrically in this pedicle, being near what may be termed its anterior surface, and the entire embryo projects like a papilla from the inner surface of the chorion into the extra-embryonic coelom. Fig. 41 is from a model of the Beneke embryo, detached from the chorion by cutting through the belly-stalk, and with the roof of the amniotic cavity removed. The embryonic disk, thus exposed, is an oval plate, resting, as it were, on the yolk-sac, and quite smooth except for a slight longi- PiG. 42. — Embryo from the Prassi Ovum, the Roof of the Amniotic Cavity HAVING BEEN REMOVED. Prom a model, b, belly-stalk; p.g., primitive groove; mg, medullary groove; «. neurenteric canal. — (Frassi.) tudinal groove upon its posterior portion. This is the primitive groove and sections passing through it show the primitive streak, consisting of a sheet of mesoderm interposed between the ectoderm and endoderm, as in the Peters embryo, and but poorly defined from the other two layers. From its anterior edge a median proc- ess extends forward for a short distance and is the head process (see p. 60). In front and to the sides of this there is as yet no mesoderm intervening between the ectoderm and endoderm. The embryonic disk of the Beneke embryo measured 0.75 mm. in length. That of an embryo described by Frassi (Fig. 42) was 1. 1 7 mm. in length, and in correspondence with its greater size, it presents some advances in structure that are of interest. As in THE MEDULLARY GROOVE 73 the younger embryo one sees a distinct primitive groove on the posterior portion of the embryonic disk, but the groove terminates anteriorly at a distinct pore («), which perforates the disk and opens ventrally into the yolk-sac. This is the neurenteric canal (see p. 6i) and in front of it a groove extends forward in the me- dian line almost to the anterior edge of the embryonic disk and is evidently the first indication of the medullary groove, whose walls are destined to give rise to the central nervous system. Sections passing through the region of the medullary groove show, lying am Pig. 43. — Section through the Prassi Embryo just in Pront of the Neuren- teric Canal. am, Amniotic cavity; gm, gastral mesoderm; hp, head process; m-p, medullary plate; ys, yolk-sac. — {Frassi.) beneath it, the head process (Fig. 43, hp), already fused with the endoderm (compare p. 61), and on each side of the process is a plate of mesoderm igm), representing the gastral mesoderm of lower forms (see Figs. 29 and 35), but not as yet showing any indications of splitting into the two layers that bound the embry- onic ccelom (see p. 62). This is just beginrring to appear in an embryo, also described by von Spee and known as embryo Gle. It measured 1.54 mm. in length and is closely similar, in general appearance, to an embryo described by Eternod and measuring 1.34 mm. in length (Fig. 44). It differs from the Frassi embryo most markedly in that the poste- rior streak region, is bent ventrally so as to lie almost at a right angle with the anterior portion. As a result the belly-stalk arises from the ventral surface of the embryo instead of from its 74 THE MEDULLARY GROOVE Pig. 44. — Embryo 1.34 mm. Long. al, AUantois; am, amnion; bs, belly-stalk; h, heart; m, medullary groove; nc, neurenteric canal; pc, caudal protuberance; ps, primitive streak; ys, yolk-stalk. — {Eternod.) THE MEDULLARY FOLDS 75 posterior extremity, near which the opening of the neurenteric canal (Fig. 43, nc) is now situated, almost the whole length of the surface seen in dorsal view being occupied by the medullary groove (m), which, in the embryo Gle, is bounded laterally by distinct ridges, the medullary folds. In the Kromer embryo Klb (Fig. 45), measuring 1.8 mm. in length, a new feature has made its appearance. The medullary folds have become quite high, and lateral to them there is on each side a series of five or six oblong elevations, which represent what are termed mesodermic somites and are due to divisions of the underlying mesoderm. Pig. 4S. — Model of the Kromer Embryo Klb seen from the Dorsal Surface, THE Roof of the Amniotic Cavity having been Removed. — (Keibel and Elze.) Instead of proceeding with a description of the external form of still older embryos it will be convenient to consider the further development of certain structures whose appearance has already been noted, namely, the head process, the medullary folds and the mesodermic somites, and first of all the medullary folds may be considered. The Medullary Folds. — The two folds are continuous ante- riorly, but behind they are at first separate, the anterior portion of the primitive streak lying between them. In forms, such as the Reptilia, which possess a distinct blastopore, this opening lies in the interval between the two, and consequently is in the floor of the medullary groove, and in the mammalia, even though no well-de- fined blastopore is formed, yet at the time of the formation of the 76 THE MEDULLARY FOLDS medullary fold an opening breaks through at the anterior end of the primitive streak in the region of Hensen's node, and places the cavity lying below the endoderm in communication with the space bounded by the medullary folds. The canal so formed is termed the neur enteric canal (Figs. 44 and 46, nc) and is so called because it unites what will later become the central canal of the nervous Pig. 46. — Diagram of a Longitudinal Section through the Embryo Gle, Meas- uring 1.54 MM. IN Length. al, Allantois; am, amnion; B, belly-stalk; ch, chorion; h, heart; nc, neurenterie canal- V, chorionic villi; Y, yolk-sac. — (von Spec.) system with the intestine (enteron) . The significance of this canal has already been discussed (p. 61); it is of very brief persistence, closing at an early stage of development so as to leave no trace of its existence. As development proceeds the medullary folds increase in height and at the same time incline toward one another (Fig. 45), so that their edges finally come into contact and later fuse, the two ecto- THE NOTOCHOED 77 dermal layers forming the one uniting with the corresponding layers of the other (Fig. 47) . By this process the medullary groove becomes converted into a medullary canal which later becomes the central canal of the spinal cord and the ventricles of the brain, the ectodermal walls of the canal thickening to give rise to the central nervous system. The closure of the groove does not, however, take place simultaneously along its entire length, but begins in what corresponds to the neck region of the adult and thence pro- ceeds both anteriorly and posteriorly, the extension of the fusion Fig. 47. — Diagrams showing the Manner of the Closure of the Medullary Groove. taking place rather slowly, however, especially anteriorly, so that an anterior opening int© the otherwise closed canal can be distinguished for a considerable period (Fig. 54). The Notochord. — ^While these changes have been taking place in the ectoderm of the median line of the embryonic disk, modifica- tions of the subjacent endoderm have also occurred. This endo- derm, it will be remembered, was formed by the head process of the primitive streak, and was a plate of cells continuous at the sides with the pimary endoderm and extending forward as far as what will eventually be the anterior part of the pharynx. Along the 78 THE NOTOCHORD line of its junction with the primary endoderm it is in relation to the medial edges of the lateral plates of mesoderm, which are comparable to the gastral mesoderm of lower forms, and it itself produces an important embryonic organ known as the notochord or chorda dorsalis, whence the term chorda endoderm sometimes applied to it. I After it has united with the primary endoderm the chorda en- doderm is a flat band, but later it becomes somewhat curved, concave towards the yolk-sack (Fig. 48, ^),and, the curvature Fig. 48. — Transverse SectiO|Ns through Mole Embryos showing the Forma- tion OF the Notochord. ec, Ectoderm; en, endoderm; m, mesoderm; nc, notochord. — {Heape.) increasing, the edges of the plate come into contact and finally fuse (Fig. 48, B) , the edges of the primary endoderm at the same time uniting beneath the chordal tube so formed, so that this layer becomes a continuous sheet, as it was at its first appearance. A distinct lumen, the secondary chordal canal, may occur in the the chordal tube, but it is soon obliterated by the enlargement of cells which bound it, and these cells later undergo a peculiar trans- formation whereby the chordal tube is converted into a solid elastic rod surrounded by a cuticular sheath secreted by the cells. The notochord lies at first immediately beneath the median line of the medullary groove, between the ectoderm and the endoderm, and has on either side of it the mesodermal plates. It does not. THE MESODERMIC SOMITES 79 however, quite reach the anterior extremity of the head, but terminates beneath the cerebral portion of the medullary canal at a point just caudad to where the hypophysis will be developed. It is a temporary structure of which only rudiments persist in the adult condition in man, but it is a structure characteristic of all vertebrate embryos and persists to a more or less perfect extent in many of the fishes, being indeed the only axial skeleton possessed by Amphioxus. In the higher vertebrates it is almost completely replaced by the vertebral column, which develops around it in a manner to be described later. The Mesodennic Somites.— Turning now to the middle germinal layer, it will be found that in it also important changes take place during the early stages of development. The probable mode of development of the extra-embryonic mesoderm and body cavity has already been described (p. 70) and attention may now be directed toward what occurs in the embryonic mesoderm. In both the Peters embryo and the embryo v.H. described by von Spee this portion of the mesoderm is represented by a plate of cells lying between the ectoderm and endoderm and continuous at the edges of the embryonic area both with the layer of extra-embryonic meso- derm which surrounds the yolk-sac and, through the mesoderm of the belly-stalk, with the chorionic mesoderm (Fig. 38). In older embryos, such as the embryo Gle of Graf Spee and the younger embryo described by Eternod (Fig. 44), the mesoderm no longer forms a continuous sheet extending completely across the em- bryonic disk, but is divided into two lateral plates, in the interval between which the ectoderm of the floor of the medullary groove and the chorda endoderm are in close contact (Fig. 49). The changes which next occur have not as yet been observed in the human embryo, though they probably resemble those described in other mammalian embryos, and the phenomena which occur in the sheep may serve to illustrate their probable nature. It has been seen that in the stage represented by the Frassi embryo a plate of mesoderm has formed on either side of the chorda endoderm, and that in a later stage, represented by the Kromer embryo Klb, differentiation occurs in these plates leading to the 8o THE MESODERMIC SOMITES formation of mesodermic somites. These make their appearance in what will later be the cervical region of the embryo and their formation proceeds backward as the body of the embryo increases in length. A longitudinal groove appears on the dorsal surface of each lateral plate of mesoderm, marking off the more median thicker portion from the lateral parts (Fig. 49), which from this stage onward may be termed the ventral mesoderm. The median or dorsal portions then become divided transversely into a number of more or less cubical masses which are termed the protoverlebrtB^ or, Fig. 49. — Transverse Section through the Second Mesodermic Somite of Sheep Embryo 3 mm. Long. am, Amnion; en, endoderm; I, intermediate cell-mass; mg, medullary groove; ms, mesodermic somite; so, somatic and sp, splanchnic layers of the ventral mesoderm, — {Bonnet.) better, mesodermic somites (Fig. 49, ms) . The cells of the somites and of the ventral mesoderm, are at first stellate in form, but later become more spindle-shaped, and those near the center of each somite and those of the ventral mesoderm arrange themselves in regular layers so as to enclose cavities which appear in these regions (Fig. 49). Each original lateral plate of gastral mesoderm thus becomes divided longitudinally into three areas, a more median area composed of mesodermic somites, lateral to this a narrow area underlying the original longitudinal groove which separated the somite area from the ventral mesoderm and which from its position is termed the intermediate cell-mass (Fig. 49, /), and, finally, the ventral mesoderm. This last portion is now divided into two lay- ers, the dorsal of which is termed the somatic mesoderm, while the THE MESODEEMIC SOMITES 8 1 ventral one is known as the splanchnic mesoderm (Fig. 49, so and sp ; and Fig. 50), the cavity which separates these two layers being the embryonic body-cavity or pleura peritoneal cavity (ccelom), which will eventually give rise to the pleural, pericardial and peritoneal cavities of the adult as well as the cavity of each tunica vaginalis testis. In the early stages of development this cavity is in wide communication with the extra-embryonic coelom, but later this communication is interrupted (see p. 89). '•#• 'm: ' •'•V ' ^'" . . / Pig. 50. — Transverse Section of an Embryo of 2.5 mm. (See Fig. 54) showing ON either side of the Medullary Canal a Mesodermic Somite, the Inter- mediate Cell-mass, and the Ventral Mesoderm. — (von Lenhossek.) Beginning in the neck region, the formation of the mesodermic somites proceeds posteriorly until finally there are present in the human embryo thirty-eight pairs in the neck and trunk regions of the body, and, in addition, a certain number are developed in what is later the occipital region of the head. Exactly how many of these occipital somites are developed is not known, but in the cow four have been observed, and there are reasons for believing that the same number occurs in the human embryo. In the lower vertebrates a number of cavities arranged in pairs occur in the more anterior portions of the head and have been homologized 6 82 THE MESODERMIC SOMITES with mesodermic somites. Whether this homology be perfectly cor- rect or not, these head-cavities, as they are termed, indicate the ex- istence of a division of the head mesoderm into somites, and although practically nothing is known as to their existence in the human embryo, yet, from the relations in which they stand to the cranial nerves and musculature in the lower forms, there is reason to suppose that they are not entirely unrepresented. Fig. 51. — Transverse Section of an Embryo of 4.25 mm. at the Level of the Arm Rudiment. A, Axial mesoderm of arm; Am, amnion; il, inner lamella of myotome; M, myo- tome; me, splanchnic mesoderm; ol, outer lamella of myotome; Pn, place of origin of pronephros; 5, sclerotome; S', defect in wall of myotome due to separation of the sclerotome; st, stomach; Vu, umbilical vein. — {Kallmann.) The mesodermic somites in the earliest human embryos in which they have been observed contain a completely closed cavity, and this is true of the majority of the somites in such a form as the sheep. In the four first-formed somites in this species, however, the somite cavity is at first continuous with the pleuroperitoneal THE MESODERMIC SOMITES 83 cavity and only later becomes separated from it, and in lower vertebrates this continuity of the somite cavities with the general body-cavity is the rule. The somite cavities are consequently to be regarded as portions of the general pleuroperitoneal cavity which have secondarily been separated off. They are, however, of but short duration and early become filled up by spindle-shaped cells derived from the walls of the somites, which themselves under- go a differentiation into distinct portions. The cells of that por- tion of the wall of each somite which is opposite the notochord become spindle-shaped and grow inward toward the median line to surround the notochord and central nervous system, and give rise eventually to the lateral half of the body of a vertebra and the corresponding portion of a vertebral arch. This portion of the somite is termed a sclerotome (Fig. 51, S), and the remainder forms a muscle plate or myotome (M) which is destined to give rise to a portion of the voluntary musculature of the body. The outer wall of the somite has been generally believed to take part in the formation of the cutis layer of the integument and hence has been termed the cutis plate or dermatome, but it seems probable that in mammals, it becomes, transformed into muscular tissue. The intermediate cell-mass in the human embryo, as in lower forms, partakes of the transverse divisions which separate the individual mesodermic somites. From one portion of the tissue in most of the somites (Fig. 51, Pn) the provisional kidneys or WolflSan bodies develop, this portion of each mass being termed a nephrotome, while the remaining portion gives rise to a mass of cells showing no tendency to arrange themselves in definite layers and constituting that form of mesoderm which has been termed mesenchyme (see p. 64). These mesenchymatous masses become converted into connective tissues and blood-vessels. The ventral mesoderm in the neck and trunk regions never becomes divided transversely into segments corresponding to the mesodermic somites, differing in this respect from the other por- tions of the lateral mesoderm. In the head, however, that portion of the middle layer which corresponds to the ventral mesoderm of the trunk does undergo a division into segments in connection 84 THE MESODERMIC SOMITES with the development of the branchial arches and clefts (see p. 93) . A consideration of these segments, which are known as the hranchiomeres, may conveniently be postponed until the chapters dealing with the development of the cranial muscles and nerves, and in what follows here attention will be confined to what occurs in the ventral mesoderm of the neck and trunk. Its splanchic layer (Fig. 52, vrn), applies itself closely to the endodermal digestive tract, which is constricted off from the dorsal portion of the yolk-sac, and becomes converted into mesenchyme out of which the muscular coats of the digestive tract develop. The cells which line the pleuroperitoneal cavity, however, retain their arrangement in a layer and form a part of the serous lining of the peritoneal and other serous cavities, the remainder of the lining being formed by the corresponding cells of the somatic layer; and in the abdominal region the superficial cells, situated near the line where the splanchnic layer passes into the somatic, and in close proximity to the nephrotome of the intermediate cell-mass, be- come columnar in shape and are converted into reproductive cells. The somatic layer, if traced peripherally, becomes continuous at the sides with the layer of mesoderm which lines the outer surface of the amnion (Fig. 51) and posteriorly with the mesoderm of the belly-stalk. That portion of it which lies within the body of the embryo, in addition to giving rise to the serous lining of the parietal layer of the pleuroperitoneum, becomes converted into mesenchyme, which for a considerable length of time is clearly differentiated into two zones, a more compact dorsal one which may be termed the somatic layer proper, and a thinner, more ventral vascular zone which is termed the membrana reuniens (Fig. 52). In the earlier stages the somatic layer proper does not extend ventrally beyond the line which passes through the limb buds and it grows out into these buds to form an axial core for them, in. which later the skeleton of the limb forms. The remain- der of the mesoderm lining the sides and ventral portions of the body-wall is at first formed from the membrana reuniens, but as development proceeds the somatic layer gradually extends more ventrally and displaces, or, more properly speaking, assimilates THE MESODERMIC SOMITES 85 into itself, the membrana reuniens until finally the latter has completely disappeared. It is to be noted that no part of the voluntary musculature of the lateral and ventral walls of the neck and trunk is derived from the somatic layer; it is formed entirely from the myotomes which gradually extend ventrally (Fig. 52) and finally come into contact with their fellows of the opposite side in the mid-ventral line. Whether the voluntary musculature of the limbs is also derived from the myotomes is at present doubtful. It has been very generally beUeved that the myotomes in their growth ven- trally sent prolongations into the limb buds which invested the Pig. 52. — Diagrams Illustrating the History of the Gastral Mesoderm. dM, dorsal portion of myotome; gr, genital ridge; J, intestine; M, myotome, mr, membrana reuniens; N, nervous system; SC, sclerotome; Sm, somatic mesoderm; vm, splanchnic mesoderm; vM, ventral portion of myotome; Wd, Wolffian duct. axial core of mesenchyme and eventually gave rise to the voluntary muscles. The actual existence of the prolongations of the myo- tomes and their conversion into the limb musculature has, how- ever, not yet been observed and it is quite probable that the limb musculature may be derived from the axial core of somatic meso- derm from which the limb skeleton develops. The appearance of the mesodermic somites is an important phenomenon in the development of the embryo, since it influences fundamentally the future structure of the organism. If each pair 86 THE MESODERMIC SOMITES of mesodermic somites be regarded as a structural unit and termed a metamere or segment, then it may be said that the body is com- posed of a series of metameres, each more or less closely resembling its fellows, and succeeding one another at regular intervals. Each somite differentiates, as has been stated, into a sclerotome and a myotome, and, accordingly, there will primarily be as many verte- bras and muscle segments as there are mesodermic somites, or, in other words, the axial skeleton and the voluntary muscles of the trunk are primarily metameric. Nor is this all. Since each metamere is a distinct unit, it must possess its own supply of nutri- tion, and hence the primary arrangement of the blood-vessels is also metameric, a branch passing off on either side from the main longitudinal arteries and veins to each metamere. And, further, each pair of muscle segments receives its own nerves, so that the •arrangement of the nerves, again, is distinctly metameric. It is to be noted that this metamerism is essentially resident in the dorsal mesoderm, the segmentation shown by structures derived from other embryonic tissues being secondary and asso- ciated with the relations of these structures to the mesodermic somites. The metamerism is most distinct in the neck and trunk regions, and at first only in the dorsal portions of these regions, the ventral portions showing metamerism only after the extension into them of the myotomes. But there is clear evidence that the arrangement extends also into the head, and that a portion of its mesoderm is to be regarded as composed of metameres. It has been seen that in the notochordal region of the head of lower vertebrates mesodermic somites are present, while anteriorly in the praechordal region there are head-cavities which resemble closely the mesodermic somites, and are probably directly com- parable to the somites of the trunk. There is reason, therefore, for beheving that the fundamental arrangement of the dorsal mesoderm in all parts of the body is metameric, but though this arrangement is clearly defined in early embryos, it loses distinct- ness in later periods of development. But even in the adult the original metamerism is clearly indicated in the arrangement of the nerves and of parts of the axial skeleton, and careful study LITERATURE 87 frequently reveals indications of it in highly modified muscles and blood-vessels. In the head the development of the branchial arches and clefts produces a series of parts presenting many of the peculiarities of metameres, and, indeed, it has been a very general custom to regard them as expressions of the general metamerism which pre- vails throughout the body. It is to be noted, however, that they are produced by the segmentation of the ventral mesoderm, a structure which in the neck and trunk regions does not share in the general metamerism, and, furthermore, recent observations on the cranial nerves seem to indicate that these branchiomeres cannot be regarded as portions of the head metameres or even as structures comparable to these. They represent, more probably, a second metamerism superposed upon the more general one, or, indeed, possibly more primitive than it, but whose relations can only be properly understood in connection with a study of the cranial nerves. LITERATURE In addition to many of the papers cited in the list at the close of Chapter II, the following may be mentioned: C. R. Baedeen: "The Development of the Musculature of the Body Wall in the Pig, etc.," Johns Hopkins Bosp. Rep., ix, 1900. T. H. Bryce and J. H. Teaches: " Contributions to the Study of the Early Develop- ment and Imbedding of the Human Ovum," Glasgow, 1908. A. C. F. Eteenod: "Communication sur un ceuf humainavec embryon excessive- ment jeune," Arch. Ital. de Biologic, xxn, 1895. A. C. F. Eternod: "II y a un canal notochordal dans I'embryon humain," Anat. Anzeiger, xvi, 1899. A. C. F. Eternod: "Les premiers stades du developpement de I'oeuf humain," Trans. Internal. Congr. Med. London, Sect. I, pt. i, 1913. Fetzer: "Ueber ein durch Operation gewonnenes menschliches Ei das in seiner Entwickelung etwa dem Petersschen Ei entspricht," Verh. Anal. Gesellschaft, XXIV, 1901. L. Frassi: "Weitere Ergebnisse des Studiums eines jungen menschlichen Eies in situ," Arch.f. mikr. Anat., lxxi, 1908.. O. Grosser: "Ein menschlicher Embryo mit Chordakanal," Anat. Hefte,XLVU, 1913. W. Heape: "The Development of the Mole (Talpa Europaea)," Quarterly Journ. Microsc. Science, xxwii, 1887. M. Herzog: "A contribution to our Knowledge of the Earliest Known Stages of Placentation and Embryonic Development in Man," Amer. Journ. Anat., ix, 1909. 88 LITERATURE P. Jung : " Beitrage zur friihesten Eieinbettung beim menschlichen Weibe," Berlin, 1908. F. Keibel: "Zur Entwickelungsgeschichte der Chorda bei Saugern (Meerschein- chen und Kaninchen)," ArchivfUr Anai. und Physiol., Anat. Abth., 1889. S. Kaestner: "Ueber die Bildung von animalen Muskelfasern aus dem Urwirbel," Arch.fiir Anat. undPhys., Anat. Abth., SuppL, 1890. J. Kollmakn: "Die Rumpfsegmente menschlicher Embryonen von 13 bis 35 Urwir- beln," Archiv fur Anat. undPhysiol., Anat. Abth., 1891. Linzenmeier: "Ein jungts menschiiches Eies in situ," Arch, filr Gynaek, cii, 1914. H. Peters: "Ueber die Einbettung des menschlichen Eies und das friiheste bisher bekannte menschliche Placentarstadium," Leipzig und Wien, 1899. F. Grap von Spee: " Beobachtungen an einer menschlichen Keimscheibe mit offener MeduUarrinne und Canalis neurentericus," Arch.f. Anat. u. Phys., Anat. Abth., 1889. F. Graf von Spee: "Ueber friihe Entwicklungsstufen des menschlichen Eies," Arch. f. Anat. u. Phys., Anat. Abth., 1896. H. Strahl and R. Beneke: "Ein junger menschlicher Embryo," Wiesbaden, 1910. J. W. VAN Wijhe: "Ueber die Mesodermsegmente des Rumpfes und die Entwick- lung des Excretionsystems bei Selachiern," Archiv fiir mikrosk. Anat., xxxm, 1889. K. W. Zimmermann: "Ueber Kopfhbhlenrudimente beim Menschen,'' Archiv fiir mikrosk. Anat., mi, 1898. CHAPIER IV THE DEVELOPMENT OF THE EXTERNAL FORM OF THE HUMAN EMBRYO In the preceding chapter descriptions have been given of human embryos representing the earlier known stages and the development of the general form of the human embryo has been traced up to the time when the mesodermic somites have made their appearance. It will now be convenient to continue the his- tory of the general development up to the stage when the embryo becomes a fetus. In the earlier stages, that is to say up to that represented by the Eternod embryo (Fig. 44), the embryonic disk may be de- scribed as floating upon the surface of the yolk-sac, and while this description still holds good for the Eternod embryo a distinct groove may be seen in that embryo between the peripheral portions of the embryonic disk and the upper part of the sac. This groove marks the beginning of the separation or constriction of the em- bryo from the yolk-sac, the result of which is the transformation of the discoidal embryonic portion of the embryonic disk into a cylindrical structure. Primarily this depends upon the deepening of the furrow which surrounds the embryonic area, the edges of this area being thus bent in on all sides toward the yolk-sac. This bending in proceeds most rapidly at the anterior end of the body, as shown in the diagrams (Fig. 53), and less rapidly at the pos- terior end where the belly-stalk is situated, and produces a con- striction of the yolk-sac, the portion of this structure nearest the embryonic disk becoming enclosed within the body of the embryo to form the digestive tract, while the remainder is converted into a pedicle-like portion, the yolk-stalk, at the extremity of which is the yolk-vesicle. The further continuance of the folding in of the edges of the embryonic area leads to an almost complete closing 89 9° DEVELOPMENT OF EXTERNAL FORM in of the embryonic ccelom and reduces the opening through which the yolk-stalk and belly-stalk communicate with the embryonic tissues to a small area known as the umbilicus. In the Kromer embryo Klb (Fig. 45) this separation of the embryo proper from the yolk-sac has proceeded to such an extent that both extremities of the embryonic disk are free from the yolk- sac, and the anterior extremity is bent ventrally almost at a right angle to the rest of the disk, producing what is termed the vertex bend, a feature characteristic of all later embryos. The marked Fig. S3. — Diagrams Illustrating the Constriction of the Embryo from the Yolk-sac. A and C are longitudinal, and B and D transverse sections. B is drawn to a larger scale than the other figures. development in this embryo of the medullary folds and the occur- rence of mesodermic somites have already been mentioned (p. 75). Somewhat more advanced is the BuUe embryo described by Kollmann and shown from the side and dorsally in Fig. 54, the greater part of the yolk-sac having been removed as well as the most of the amnion. The embryo measured about 2.5 mm. in length aiid showed a considerable increase in the number of meso- dermic somites, there being about fourteen of them on either side. Posteriorly the medullary groove has become converted into a medullary canal by the medullary folds meeting over it and fusing, DEVELOPMENT OE EXTERNAL FORM 91 but anteriorly it is still open. The vertex bend is well marked and immediately behind the tip of the head, on the ventral surface of the body, there may be seen a well-marked depression, the oral fossa, between which and the anterior surface of the yolk-sac is a am Pig. 54. — Embryo 2.5 mm. Long. am. Amnion; B, belly-stalk; k, heart; M, closed, and M', still open portions of the medullary groove; Om, vitelline vein; OS, oral fossa; Y, yolk-sac. — (KoUmann.) rounded elevation due to the formation of the heart. Attention may be called to the fact that the position of this organ is far forward of that which it will eventually occupy, so that it must undergo a marked retrogression during later development. 92 DEVELOPMENT OF EXTERNAL FORM Pig. 5S.^Embryo Lr, 4.2 mm. Long. am. Amnion; au, auditory capsule; B, belly-stalk; h, heart; LI, lower, and ul, upper limb; Y, yolk-sac. — (His.) DEVELOPMENT OE EXTERNAL FORM 9^ As an example of a later stage of development the embryo Lr of His, measuring 4.2 mm. in length, may be taken (Fig. 55). In this the constriction of the yolk-sac has progressed so far that its proximal portion may now be spoken of as the yolk-stalk. The mesodermic somites have undergone a further increase and have almost reached their final number, the vertex bend has become still more pronounced and the medullary groove, throughout its entire length, has been converted into the medullary canal, which, anteriorly, shows distinct enlargements and constrictions which foreshadow various portions of the future brain. The auditory organ, which made its appearance in earlier stages, has now become quite distinct, and a lateral bulging of the most anterior portion of the head indicates the position of the future eye. In addition certain other important features have now ap- peared. Thus, about opposite the heart a second bend, the nape bend, is becoming visible on the dorsal surface of the body and toward the posterior end a distinct sacral lend is evident. Sec- ondly, a little posterior to the level of the nape bend a slight elevation is to be seen on the side of the body; this is the limb bud for the upper limb and a corresponding, though smaller, elevation in the region of the sacral bend represents the lower Hmb. Thirdly, three grooves having a dorso-ventral direction have appeared on the sides of what will be the future pharyngeal region. These are representatives of a series of branchial clefts, structures that are of great morphological importance in the further develop- ment inasmuch as they determine to a large extent the arrange- ment of various organs of the head region. They represent the clefts which exist in the walls of the pharynx in fishes, through which water, taken in at the mouth, passes to the exterior, bathing on its way the gill filaments attached to the bars or arches, as they are termed, which separate successive clefts. Hence the name "branchial" which is applied to them, though in the mam- mals they never have respiratory functions to perform, but, ap- pearing, persist for a time and then either disappear or are applied to some entirely different purpose. Indeed, in man they are never really clefts but merely grooves, and corresponding to each groove 94 DEVELOPMENT OF EXTERNAL FORM iTTfSpit^-i &fc f ' <*. ^sA Fig. 56. — Floor of the Pharynx OF Embryo B, 7 mm. Long. Ep, Epiglottis; Sp, sinus praecer- vicalis; V-, tuberculum impar; V^, posterior portions of the tongue; /, //, 77/, and IV, branchial arches. — {His.) in the ectoderm there is also one in the subjacent endoderm of what will eventually be the pharyngeal region of the digestive tract, so that in the region of each cleft the ectoderm and endo- derm are in close relation, being separated only by a very thin layer of mesoderm. In the intervals between successive clefts a more considerable amount of mesoderm is present (Fig. 56). In the human embryo four clefts and five branchial arches develop on each side of the body, the last arch lying posteriorly to the fourth cleft and not being very sharply de- fined along its posterior margin. As just stated, the clefts are nor- mally merely grooves, and iji later development either disappear or are converted into special structures. Occasionally, however, a cleft may persist and the thin membrane which forms its floor may become perforated so that an opening from the exterior into the pharynx occurs at the side of the neck, forming what is termed a branchial fistula. Such an abnormality is most fre- quently developed from the lower (ventral) part of the first cleft; normally this disappears, the upper portion of the cleft persisting, however, to form the external auditory meatus and tympanic cavity. A further stage in the differentiation of these clefts and arches is shown by the embryo represented in Fig. 57. The nape bend has now increased to such an exent that the whole anterior part of the body is bent at a right angle to the middle part and the entire embryo is coiled in a spiral manner. The limb buds are much more distinct than in the previous stage and four branchial arches are now present; the second and third have become more defined and a strong process has developed from the dorsal part of the anterior border of the first one, which has thus become somewhat A-shaped. The anterior limb of each A is destined to give rise to the upper jaw, and hence is known as the maxillary process, while the posterior limb represents the future lower jaw and is termed the mandibular process. DEVELOPMENT OF EXIERNAL FORM 95 In the stage represented by this embryo the closing in of the embryonic coelom has progressed to such a degree that only a small opening is left in the ventral body-wall of the embryo through which the yolk-stalk and its accompanying vessels and the belly-stalk pass. Indeed the margins of the umbilicus may have begun to be prolonged outward over these structures, enclosing them in a cylindrical investment, the first stage of what will later be the umbilical cord being thus established. Pig. 57. — Embryo Backer 7.3 mm. in Length. X 5- — (Keibel and Elze.) Leaving aside for the present all consideration of the further development of the limbs and branchial arches, the further evolu- tion of the general form of the body may be rapidly sketched. In an embryo (Fig. 58) from Ruga's collection, described and figured by His and measuring 9.1 mm. in length,* the prolongation of the * This rheasurement is taken in a straight line from the most anterior portion of the nape bend to the middle point of the sacral bend and does not follow the curva- ture of the embryo. It may be spoken of as the nape-rump length and is convenient for use during the stages when the embryo is coiled upon itself. 96 DEVELOPMENT OF EXTERNAL FORM margins of the umbilicus has increased until more than half the yolk-stalk has become enclosed within the umbilical cord. The nape and sacral bends are still very pronounced, although the em- bryo is beginning to straighten out and is not quite so much coiled as in the preceding stage. At the posterior end of the body there has developed a rather abruptly conical tail filament, in the place of Pig. 58. — Embryo 9.1 mm. Long. LI, Lower limb; U, umbilical cord; Ul, upper limb; Y, yolk-sac- -{His.) the blunt and gradually tapering termination seen in earlier stages, and a well-marked rotundity of the abdomen, due to the rapidly increasing size of the liver, begins to become evident. In later stages the enclosure of the yolk- and belly-stalks within the umbilical cord proceeds until finally the cord is complete through the entire interval between the embryo and the wall of the ovum. At the same time the straightening out of the embryo continues, as may be seen in Fig, 59 representing the embryo xlv DEVELOPMENT OF EXTERNAL FORM 97 (Bra) of His, which shows also, both in front of and behind the neck bend, a distinct depression, the more anterior being the occipital and the more posterior the nape depression; both these depressions are the indications of changes taking place in the central nervous system. , The tail filament has become more marked, and in the '1i%aSf* region a slight ridge surrounding the eyeball and marking out the conjunctival area has appeared; a depression anterior to the nasal fossae marks off the nose from the forehead ; and the external ear, whose development will be consid- Fic. 59. — Embryo Br2, 13.6 mm. Long. — (His.) ered later on, has become quite distinct. This embryo had a nape-rump length of 13.6 mm. In the embryos S2 and L3 (Fig. 60, A and B) of His' collection the straightening out of the nape bend is proceeding, and indeed is almost completed in embryo L3, which begins to resemble closely the fully formed fetus. The tail filament, somewhat reduced in size, still persists and the rotundity of the abdomen continues to be well marked. The neck region is beginning to be distinguishable in embryo S2 and in embryo L3 the eyelids have appeared as slight folds surrounding the conjunctival area. The nose and forehead are clearly defined by the greater development of the nasal groove 98 DEVELOPMENT OF EXTERNAL FORM and the nose has also become raised above the general surface of the face, while the external ear has almost acquired its final fetal form. These embryos measure respectively about 15 and 17.5 mm. in length.* Finally, an embryo — again one of those described by His, namely, his Wt, having a length of 23 mm. — may be figured (Fig. 61) as representing the practical acquisition of the fetal Fig. 6o.- -A, Embryo S2. 15 mm. Long (showing Ectopia of the Heart); B. Embryo Lj, 17.5 mm. Long. — (His.) form. This embryo dates from about the end of the second month of pregnancy, and from this period onward it is proper to use the term fetus rather than that of embryo. |The changes which have been described in preceding stages are now complete and it remains only to be mentioned that the caudal filament, which is still prominent, gradually disappears in later stages, becoming, as it were, submerged and concealed beneath adjacent parts by the development of the buttocks. The incompleteness * The embryo S2 presents a slight abnormality in the great projection of the heart, but otherwise it appears to be normal. DEVELOPMENT OF THE BRANCHIAL ARCHES 99 of the development of these regions in embryo Wt is manifest, not only from the projection of the tail filament, but also from the external genitalia being still largely visible in a side view of the embryo, a condition which will disappear in later stages. Pig. 6i. — Embryo Wt, 23 mm. Long. — (His.) The Later Development of the Branchial Arches, and the Development of the Face.— In the embryo shown in Fig. 57, the four branchial clefts and five arches which develop in the human embryo are visible in surface views, but in the Ruge embryo (Fig. 58) it will be noticed that only the first two arches, the first with a well-developed maxillary process, and the cleft separating them can be distinguished. This is due to a sinking inward of the region occupied by the three posterior arches so that a triangular depres- lOO DEVELOPMENT OF THE BRANCHIAL ARCHES sion, the sinus pracerdcalis, is formed on each side of what will later become the anterior part of the neck region. This is well shown in an embryo (Br2) described by His which measured 6.9 mm. in length and of which the anterior portion is shown in Fig. 62. The anterior boundary of the sinus {ps) is formed by the posterior edge of the second arch and its posterior boundary by the thoracic wall, and in later stages these two boundaries gradu- ally approach one another so as first of all to diminish the opening into the sinus and later to completely obliterate it by fusing to- pic. 62. — Head of Embryo of 6.9 mm. «o, Nasal pit; ps, prsecervical sinus. — {His.) gether, the sinus, thus becoming converted into a completely closed cavity whose floor is formed by the ectoderm covering the three posterior arches and the clefts separating these. This cavity eventually undergoes degeneration, no traces of it occurring nor- mally in the adult, although certain cysts occasionally observed in the sides of the neck may represent persisting portions of it. A somewhat similar process results in the closure of the ventral portion of the first cleft,* a fold growing backward from the pos- * See page 94, small type. DEVELOPMENT OF THE BRANCHIAL ARCHES lOI terior edge of the first arch and fusing with the ventral part of the anterior border of the second arch. The upper part of the cleft persists, however, and, as already stated, forms the external auditory meatus, the pinna of the ear being developed from the adjacent parts of the first and second arches (Figs. 59 and 60). The region immediately in front of the first arch is occupied by a rather deep depression, the oral fossa, whose early develop- ment has already been noticed. In an embryo measuring 8 mm. i21Xp--\ Fig. 63. — Face of Embryo of 8 mm. mxp. Maxillary process; np, nasal pit; os, oral fossa; pg, processus globularis. — {His. in length (Fig. 63) the fossa {os) has assumed a somewhat irregular quadrilateral form. Its posterior boundary is formed by the mandibular processes of the first arch, while laterally it is bounded by the maxillary processes {mxp) and anteriorly by the free edge of a median plate, termed the nasal process, which on either side of the median line is elevated to form a marked protuberance', the processus glohularis {pg). The ventral ends of the maxillary processes are widely separated, the nasal process and the proc- essus globulares intervening between them, and they are also separated from the globular processes by a deep and rather wide groove which anteriorly opens into a circular depression, the nasal pit {np). I02 DEVELOPMENT OF THE FACE Later on the maxillary and globular processes unite, obliterat- ing the groove and cutting off the nasal pits — which have by this time deepened to form the nasal fossae — from direct communica- tion with the mouth, with which, however, they later make new communications behind the inaxillary processes, an indication of the anterior and posterior nares being thus produced. Pig. 64. — Face of Embryo after the Completion of the Upper Jaw. — {His.) Occasionally the maxillary and globular processes fail to unite on one or both sides, producing a condition popularly known as "harelip." At the time when this fusion occurs the nasal fossae are widely separated by the broad nasal process (Fig. 64), but during later development this process narrows to form the nasal septum and is gradually elevated above the general surface of the face as shown in Figs. 59-61. By the narrowing of the nasal process the globular processes are brought nearer together and form the por- tions of the upper Jaw immediately on each side of the median DEVELOPMENT OF THE LIMBS I03 line, the rest of the jaw being formed by the maxillary processes. In the meantime a furrow has appeared upon the mandibular process, running parallel with its borders (Fig. 60) ; the portion of the process in front of this furrow gives rise to the lower lip and is known as the lip ridge, while the portion behind the furrow be- comes the lower jaw proper and is termed the chin ridge. The Development of the Limbs. — As has been already pointed out, the limbs make their appearance in an embryo measuring about 4 mm. in length (Fig. 55) and are at first bud-like in form. As they increase in length they at first have their long axes directed parallel to the longitudinal axis of the body and become somewhat flattened at their free ends, remaining cylindrical in their proximal portions. A furrow or constriction appears at the junction of the flattened and cylindrical portions (F'g. 58) , and later a second con- striction divides the cylindrical portion into a proximal and distal moiety, the three segments of each limb — the arm, forearm, and hand in the upper limb, and the thigh, leg, and foot in the lower — being thus marked out. The digits are first indicated by the de- velopment of four radiating shallow grooves upon the hand and foot regions (Fig. 59) , and a transverse furrow uniting the proximal ends of the digital furrows indicates the junction of the digital and palmar regions of the hand or of the toes and body of the foot. After this stage is reached the development of the upper limb proceeds more rapidly than that of the lower, although the processes are essentially the same in both limbs. The digits begin to project slightly, but are at first to a very considerable extent united together by a web, whose further growth, however, does not keep pace with that of the digits, these thus coming to project more and more in later stages. Even in comparatively early stages the thumb, and to a somewhat slighter extent the great toe, is widely separated from the second digit (Figs. 60 and 61). While these changes have been taking place the entire limbs have altered their position with reference to the axis of the body, being in stages later than that shown in Fig. 58 directed ventrally so that their longitudinal axes are at right angles to that of the I04 DEVELOPMENT OF THE LIMBS body. From the figures of later stages it may be seen that it is the thumb (radial) side of the arm and the great toe (tibial) side of the leg which are directed forward; the plantar and palmar surfaces of the feet and hands are turned toward the body and the elbow is directed outward and slightly backward, while the knee looks outward and slightly forward. It seems proper to conclude that the radial side of the arm is homologous with phe tibial side of the leg, the palmar surface of the hand with the plantar surface of the foot, and the elbow with the knee. The limbs are not yet, however, in their final position but must undergo a second alteration, whereby their long axes again become parallel with that of the body. This is accomplished by a rotation of the limbs around' axes passing through the shoulder- and hip- joints, together with a rotation about their longitudinal axes through an angle of 90 degrees. This axial rotation of the upper limb is, however, in exactly the opposite direction to that of the lower limb of the corresponding side, so that the homologous surfaces of the two limbs have entirely different relations, the radial side of the arm, for instance, being the outer side while the tibial side of the leg is the inner side, and whereas the palmar sur- face of the hand looks ventrally, the plantar surface of the foot looks dorsally. In making these statements no account is taken of the sec- ondary position which the hand may assume as the result of its pronation; the positions given are those assumed by the limbs when both the bones of their middle segment are parallel to one another. It may be pointed out that the prevalent use of the physiological terms flexor and extensor to describe the surfaces of the limbs has a tendency to obscure their true morphological relationships. Thus if, as is usual, the dorsal surface of the arm be termed its extensor surface, then the same term should be applied to the entire ventral surface of the leg, and all movements of the lower limb ventrally should be spoken of as movements of extension and any movement dorsally as movements of flexion. And yet a ventral movement of the thigh is generally spoken of as a flexion of the hip-joint, while a straightening out of the foot upon the leg — that is to say, a movement of it dorsally — is termed its extension. AGE OF EMBRYO AT DIFFERENT STAGES 105 The Age of the Embryo at Different Stages. — The age of an embryo is a matter of considerable moment to the embryologist who desires to trace the successive stages in the development of any organ. In the case of the human embryo an exact determina- tion of the age is somewhat difficult, since in the majority of cases the only available datum from which it may be estimated is the time of the cessation of the menses. From what has already been said (pp. 28, 37) it is evident that this menstruation age (Mall) can only be approximative to the actual age, which should date from the moment of fertilization. The available evidence (see p. 28) indicates that ovulation takes place at some time in the inter- menstrual period, on the average about the middle of its duration, but since this duration is about two weeks the limits of variation from the average must be quite large, too large to be of much value in the case of young embryos, where a day means much. The earlier attempts at estimating the ages of young human embryos, those of His for instance, were based on the belief that ovulation took place as a rule immediately before menstruation, and if fertilization occurred the menses were omitted. On this basis His estimated embryos of 2.2 to 3.0 mm. to be two to two and a half weeks old, those of 5.0 to 6.0 mm. to be about three and one-half weeks and those of 10. o to ii.o mm. to be about four and one-half weeks. It is certain, however, that such ages are decidedly too low, perhaps by as much as a week. A small number of cases are on record in which the date of the coition that led to the pregnancy is definitely known. This copulation age does not necessarily give the exact fertilization age, but it is probably within one, or at most two, days of it (see p. 36). The Bryce-Teacher ovum, with an embryo measuring 0.15 mm. in length, was the result of a coition that took place 16 days before the ovum was aborted, and the assumption that the embryo was about two weeks old cannot be far astray. Similarly an embryo described by Eternod and measuring 1.3 mm. in length was the result of a single coition occurring twenty-one days previously and its age may be set at approximately three weeks or better at eighteen or nineteen days. A later embryo which measured 25 mm. io6 AGE OF EMBRYO AT DIFFERENT STAGES crown-rump measurement, was the result of a coition that took place fifty-six days before the abortion, so that the embryo may be regarded as having been a little less than eight weeks old. These and three other similar cases may be shown in a table thus : Length of Emb. Menstruation Copulation Probable Fertiliza- Authority in mm. Age in Days Age in Days tion Age in Days About o.is 38 16 14 Bryce- Teacher 1-3 34 21 19 Eternod V. B. 8.8 42 38 36 Tandler V. B. 14.0 6S 47 4S Rabl V. B. 18.0 54 47 45 MaU V. B. 25.0 75 56 54 MaU In the fourth column two days have been taken from the copulation age to estimate the fertilization age. This may be too much in some cases and too little in others and either this or a difference in the rate of growth may account for the fact that two embryos differing in their vertex-breech measurements by 4.0 mm. appear to be of the same age. The 14.0 mm. embryo, how- ever, might be assigned a fertilization age of 44 days and the 18.0 mm. one an age of 46 days without any violation of the data. It is interesting to note the wide variation that obtains between the menstruation and copulation ages, the difference in one case being as little as four days and in another as much as twenty-two, though the average difference as determined from statistics of full-term births is about eleven days. Making all possible corrections the exact age cannot be de- termined within less than two or three days (Mall) , but in general one may say that embryos of 2.0 to 3.0 mm. may be assigned to the fourth week of development, those of 5.0 to 6.0 vertex-breech length to the latter part of the fifth week, those of lo.o mm. to the end of the sixth week and those of 25.0 to 28.0 mm. which are just passing into the fetus stage, to the end of the eighth week. As regards the later periods of development, the limits of error for any date become of less importance. Schroder gives the following measurements as the average: LITERATURE I07 3d lunar month 70-90 mm. 4th lunar month 100-170 mm. Sth lunar month 180-270 mm. 6th lunar month 280-340 mm. 7th lunar month > 350-380 mm. Sth lunar month 425 mm. gth lunar month 467 mm. loth lunar month 490-500 mm. The data concerning the weight of embryos of different ages are as yet very insufl&cient, and it is well known that the weights of new-born children may vary greatly, the authenticated ex- tremes being, according to Vierordt, 717 grams and 6123 grams. It is probable that considerable variations in weight occur also during fetal life. So far as embryos of the first two months are concerned, the data are too imperfect for tabulation; for later periods Fehling gives the following as average weights: 3d month 20 grams. 4th month 120 grams. Sth month 285 grams. 6th month 635 grams. 7th month 1220 grams. 8th month 1700 grams. gth month 2240 grams. loth month 3250 grams. and the results obtained by Jackson are essentially similar. LITERATURE In addition to the papers of Bryce and Teacher, Eternod, Fetzer, Frassi, Herzog, Peters, Von Spee, Strahl and Beneke and Grosser, cited in the preceding chapter, the following may be mentioned : J. L. Bremee: "Description of a 4 mm. Human Embryo,'' Amer. Journ. Anat., V, 1906. J. Broman: "Beobachtung eines menschlichen Embryos von beinahe 3 mm. L^nge mit specieller Bemerkung uber die bei demselben befindlichen Hirnfalten," Morpholog. Arbeiten, v, 1895. A. J. P. VAN DEN Broek: "Zur Kasuistik junger menschlicher Embryonen," Anat. Hefte, xLiv, 1911. J. M. Coste: "Histoire gfin^rale et particulifere du developpement des corps organ- ises," Paris, 1847-1859. W. E. Dandy: "A Human Embryo with Seven Pairs of Somites, Measuring about 2 mm. in Length," Amer. Journ. Anat., x, igio. Io8 LITERATURE A. Ecker: "Beitrage zur Kenntniss der ausserer Formen jungster menschlichen Embryonen," Archiv.fur Anal, und Physiol., Anat. Abth., 1880. C. Elze: "Beschreibung eines menschlichen Embryos von zirka 7 mm. grosster Lange," Anat. Hefte, xxxv, 1907. C. GiACOMiNi: "Un oeuf humain de 11 jours," Archives Ital. de Biologie, xxxix, 1898. O. Grosser: "Altersbestimmung junges menschliche Embryonen — Ovulations — und Menstruationstermin," Anat. Anzeiger, x.L\ll, 1914. V. Hensen: "Beitrag zur Morphologie der Korperform und des Gehirns des menschlichen Embryos," Archivfur Anat. und Physiol., Anal. Abth., 1877. W. His: "Anatomiemenschlicher Embryonen," Leipzig, 1880. F. Hochstetter: "Bilder der ausseren Korperform einiger menschlicher Embryo- nen aus den beiden Ersten Monaten der Entwicklung," Munich, 1907. N. W. Ingalls: "Beschreibung eines menschlichen Embryos von 4.9 mm.," Arch. fiir mikr. Anal., Lxx, 1907. C. M. Jackson: "On the Prenatal Growth of the Human Body and the Relative Growth of the Various Organs and Parts," Amer. Journ. Anat., Df, 1909. J. Janosik: "Zwei junge menschliche Embryonen," Archivfiir mikrosk. Anal., xxx, 1887. H. E. Jordan: "Description of a s mm. Human Embryo," Anal. Record, in, 1909. P. Jung: "Beitrage zur friihesten Ei-einbettung beim menschlichen Weibe," Berlin, 1908. F. Keibel: "Ein sehr junges menschliches Ei," Archivfiir Anal, und Physiol., Anal. Abth., 1890. F. Keibel: "Ueber einen menschlichen Embryo von 6.8 mm. grosster Lange," Verhandl. Anatom. Gesellsch., xin, 1899. F. Keibel and C. Elze: "Normentafeln zur Entwicklungsgeschichte der Wirbel- tiere," Heft vni, 1908. J. Kollmann: "Die Korperform menschlicher normaler und pathologischer Em- bryonen," Archivfiir Anat. und Physiol., Anat. Abth., Supplement, 1889. A. Low: "Description of a Human Embryo of 13-14 Mesodermic Somites," Journ. Anat. and Phys., xlii, 1908. F. P. Mall: "A Human Embryo Twenty-six Days Old," Journ. of Morphology, v, 1891. F. P. Mall: "A Human Embryo of the Second Week," Anat. Anzdger, vni, 1893. F. P. Mall: "Early Human Embryos and the Mode of their Preservation," Bulletin of the Johns Hopkins Hospital, iv, 1894. F. P. Mall: "On the Age of Human Embryos," Amer. Journ. Anat., xxiii, 1918. C. S. Minot: "Human Embryology," New York, 1892. J. MtJLLER: " Zerglierderungen menschlicher Embryonen aus fruherer Zeit," Archiv fiir Anat. und Physiol., 1830. C. Phisalix: "Etude d'un Embryon humain de ii millimeters," Archives de zoolog. experimentale et genSrale, SSr. 2, VI, 1888. H. Piper: "Ein menschlicher Embryo von 6.8 mm. Nackenlinie," Archivfiir Anat. und Physiol., Anat. Abth., 1898. C. Rabl: "Die Entwicklung des Gesichtes, Heft i. Das Gesicht der Saugetiere, Leipzig, 1902. LITERATURE 109 G. Retzius: "Zur Kenntniss der Entwicklung der Korperformen des Menschen wahrend der fotalen Lebensstufen," Biolog. Untersuch., xi, 1904. J. Tandler: "Ueber einen menschlichen Embryo von 38 Tage," Anat. Anzeiger, XXXI, 1907. Allen Thompson: "Contributions to the History of the Structure of the Human Ovum and Embryo before the Third Week after Conception, with a Description of Some Early Ova," Edinburgh Med. and Surg. Journal, iii, 1839. (See also Froriep's Neue Notizen, xiii, 1840). P. Thompson: Description of a human embryo of twenty-three paired somites," Journ. Anat. and Phys., xli, 1907. F. W. Thyng: "The Anatomy of a 17.8 mm. human embryo," Amer. Journ. Anal., xvn, 1914. H. Triepel: " Altersbestimmung bei menschlichen Embryonen," Anat. Anz., xlvi, 1914. H. Triepel: "Alter menschlicher Embryonen und Ovulationstermin," Anal. Anzei- ger, XLVin, 1915. I. E. Wallin; "A Human Embryo of Thirteen Somites," Amer. Journ. Anal., xv, 1913- J. C. Watt: "Description of two young twin human embryos with 17-19 paired somites," i'^J, Camepe Inst. No. 222, Conlr. to Embryol, No. 2, igis- CHAPTER V THE YOLK-STALK, BELLY-STALK, AND FETAL MEMBRANES The conditions to which the embryos and larvae of the majority of animals must adapt themselves are so different from those under which the adult organisms exist that in the early stages of de- velopment special organs are very frequently developed which are of use only during the embryonic or larval period and are dis- carded when more advanced stages of development have been reached. This remark applies with especial force to the human embryo which leads for a period of nine months what may be termed a parasitic existence, drawing its nutrition from and yielding up its waste products to the blood of the parent. In order that this may be accomplished certain special organs are developed by the embryo, by means of which it forms an intimate connection with the walls of the uterus, which, on its part, be- comes greatly modified, the combination of embryonic and ma- ternal structures producing what are termed the deciduce, owing to their being discarded when at birth the parasitic mode of life is given up. Furthermore, it has already been seen that many peculiar modifications of development in the human embryo result from the inheritance of structures from more or less remote ancestors, and among the embryonic adnexes are found structures which represent in a more or less modified condition organs of con- siderable functional importance in lower forms. Such structures are the yolk-stalk and vesicle, the amnion, and the allantois, and for their proper understanding it will be well to consider briefly their development in .some lower form, such as the chick. At the time when the embryo of the chick begins to be con- stricted off from the surface of the large yolk-mass, a fold, con- no YOLK-STALK AND FETAL MEMBRANES III sisting of ectoderm and somatic mesoderm, arises just outside the embryonic area, which it completely surrounds. As develop- ment proceeds the fold becomes higher and its edges gradually draw nearer together over the dorsal surface of the embryo (Fig. 65, A, Af), and finally meet and fuse (Fig. 65, B and C), so that the embryo becomes enclosed within a sac, which is termed the amnion and is formed by the fusion of the layers which consti- tuted the inner wall of the fold. The layers of the outer wall of the fold after fusion form part of the general ectoderm and somatic Pig. 65. — Diagrams Illustrating the Formation of the Amnion and Allantois IN THE Chick. Af, Amnion folds; Al, allantois; Am, amniotic cavity; Ds, yolk-sac. — (Gegenbaur.) mesoderm which make up the outer wall of the ovum and together are known as the serosa, corresponding to the chorion of the mammalian embryo. The space which occurs between the am- nion and the serosa is a portion of the extra-embryonic ccelom, and is continuous with the embryonic pleuroperitoneal cavity. In the ovum of the chick, as in that of the reptile, the proto- plasmic material is limited to one pole and rests upon the large yolk-mass. As development proceeds the germ layers gradu- ally extend around the yolk-mass and eventually completely en- 112 THE AMNION close it, the yolk-mass coming to lie within the endodennal layer, which, together with the splanchnic mesoderm which lines it, forms what is termed the yolk-sac. As the embryo separates from the yolk-mass the yolk-sac is constricted in its proximal portion and so differentiated into a yolk-stalk and a yolk-sac, the contents of the latter being gradually absorbed by the embryo during its growth, its walls and those of the stalk being converted into a portion of the embryonic digestive tract. In the meantime, however, from the posterior portion of the digestive tract, behind the point of attachment of the yolk-sac, a diverticulum has begun to form (Fig. 65, A, At). This increases in size, projecting into the extra-embryonic portion of the pleuro- peritoneal cavity and pushing before it the splanchnic mesoderm which lines the endoderm (Fig. 65, B and C). This is the allan- tois, which, reaching a very considerable size in the chick and applying itself closely to the inside of the serosa, serves as a respi- ratory and excretory organ for the embryo, for which purpose its walls are richly supplied with blood-vessels, the allantoic arteries and veins. Toward the end of the incubation period both the amnion and allantois begin to undergo retrogressive changes, and just before the hatching of the young chick they become completely dried up and closely adherent to the egg-shell, at the same time separating from their point of attachment to the body of the young chick, so that when the chick leaves the egg-shell it bursts through the dried-up membranes and leaves them behind as useless structures. The Amnion. — Turning now to the human embryo, it will be found that the same organs are present, though somewhat modified either in the mode or the extent of their development. A well developed amnion occurs, arising, however, in a very different manner from what it does in the chick; a large yolk-sac occurs even though it contains no yolk; and an allantois which has no respira- tory or excretory functions is present, though in a somewhat degenerated condition. It has been seen from the description of the earHest stages of development that the processes which occur in the lower forms are greatly abbreviated in the human embryo. THE AMNION II3 The enveloping layer, instead of gradually extending from one pole to enclose the entire ovum, develops in situ during the stages immediately succeeding segmentation, and the extra-embryonic mesoderm, instead of growing out from the embryo to enclose the yolk-sac, apparently also undergoes a precocious development in situ. The earliest stages in the development of the amnion are not yet known for the human embryo, but from the condition in which it is found in the Peters embryo (Fig. 38) and in the embryo v.H. of von Spec (Fig. 40) it is probable that it arises, not by the fusion of the edges of a fold, as in the chick, but by a vacuolization of a portion of the inner cell-mass, as has been de- scribed as occurring in the bat (p. 57). It is, then, a closed cavity from the very beginning, the floor of the cavity being formed by the embryonic disk, its posterior' wall by the anterior surface of the belly-stalk, while its roof and sides are thin and composed of a single layer of flattened ectodermal cells lined on the outside by a layer of mesoderm continuous with the somatic mesoderm of the embryo and the mesoderm of the belly-stalk (Fig. 66, A). When the bending downward of the peripheral portions of the embryonic disk to close in the ventral surface of the embryo oc- curs, the line of attachment of the amnion to the disk is also carried ventrally (Fig. 66, B), so that when the constriction off of the embryo is practically completed, the amnion is attached anteriorly to the margin of the umbilicus and posteriorly to the extremity of the band of ectoderm lining what may now be con- sidered the posterior surface of the belly-stalk, while at the sides it is attached along an oblique line joining these two points (Fig. 66, B and C, in which the attachment of the amnion is indicated by the broken line) . ' Leaving aside for the present the changes which occur in the attachment of the amnion to the embryo (see p. 119), it may be said that during the later growth of the embryo the amniotic cavity increases in size until finally its walls come into contact with the chorion, the extra-embryonic body-cavity being thus practically obliterated (Fig. 66, D), though no actual fusion of amnion and chorion occurs. Suspended by the umbilical cord 114 THE AMNION which has by this time developed, the embryo floats freely in the amniotic cavity, which is filled by a fluid, the liquor amnii, whose origin is involved in doubt, some authors maintaining that it in- filtrates into the cavity from the maternal tissues, while others hold that a certain amount of it at least is derived from the em- FiG. 66. — Diagrams Illustrating the Formation of the Umbilical Cord. The heavy black line represents the embryonic ectoderm; the dotted line repre- sents the line o£ reflexion of the body ectoderm into that of the amnion. Ac, Amniotic cavity; Al, allantois; Be, extra-embryonic coelum; Bs, belly-stalk; Ch, horion; P, placenta; Uc, umbilical chord; V, chorionic villi; Ys, yolk-sac. bryo. It is a fluid with a specific gravity of about 1.003 ^^^ con- tains about I per cent, of solids, principally albumin, grape-sugar, and urea, the last constituent probably coming from the embryo. When present in greatest quantity — that is to say, at about the beginning of the last month of pregnancy — it varies in amount between one-half and three-fourths of a liter, but during the last month it diminishes to about half that quantity. To protect the THE YOLK-SAC US epidermis of the fetus from maceration during its prolonged im- mersion in the liquor amnii, the sebaceous glands of the skin at about the sixth month of development pour out upon the surface of the body a white fatty secretion known as the vernix caseosa. During parturition the amnion, as a rule, ruptures as the re- sult of the contraction of the uterine walls and the liquor amnii escapes as the "waters,'' a phenomenon which normally precedes the delivery of the child. As a rule, the rupture is sufficiently ex- tensive to allow the passage of the child, the amnion remaining behind in the uterus, to be subsequently expelled along with the deciduae. Occasionally it happens, however, that the amnion is suflSciently strong to withstand the pressure exerted upon it by the uterine con- tractions and the child is born still enveloped in the amnion, which, in such cases, is popularly known as the "caul," the possession of which, according to an old superstition, marks the child as a favorite of fortune. As stated above, the liquor amnii varies considerably in amount in different cases, and occasionally it may be present in excessive quanti- ties, producing a condition known as hydramnios. On the other hand, the amount may fall considerably below the normal, in which case the amnion may form abnormal unions with the embryo, sometimes pro- ducing malformations. Occasionally also bands of a fibrous character traverse the amniotic cavity and, tightening upon the embiyo during its growth, may produce various malformations, such as scars, splitting of the eye lids or lips, or even amputation of a Umb. The Yolk-sac. — The probable mode of development of the yolk-sac in the human embryo, and its differentiation into yolk- stalk and yolk- vesicle have already been described (p. 89). Wheii these changes have been completed, the vesicle is a small pyriform structure lying between the amnion and the chorionic mesoderm, some distance away from the extremity of the umbilical cord (Fig. 66, D), and the stalk is a long slender column of cells extending from the vesicle through the umbilical cord to unite with the in- testinal tract of the embryo. The vesicle persists until birth and may be found among the decidual tissues as a small sac measuring from 3 to 10 mm. in its longest diameter. The stalk, however, early undergoes degeneration, the lumen which it at first contains Il6 THE ALLANTOIS AND BELLY-STALK becoming obliterated and its endoderm also disappearing as early as the end of the second month of development. The portion of the stalk which extends from the umbilicus to the intestine usually shares in the degeneration and disappears, but in about 3 per cent, of cases it persists, forming a more or less extensive diverticulum of the lower part of the small intestine, sometimes only half an inch or so in length and sometimes much larger. It may or may not retain connection with the abdominal wall at the umbilicus, and is known as Meckel's diverticulum. This embryonic rudiment is of no little importance, since, when present, it is apt to undergo invagination into the lumen of the small intestine and so occlude it. How frequently this happens relatively to the occurrence of the diverticulum may be judged from the fact that out of one hundred cases of occlusion of the small intestine six were due to an invagination of the diverticulum. In the reptiles and birds the yolk-sac is abundantly supplied with blood-vessels by means of which the absorption of the yolk is carried on, and even although the functional importance of the yolk-sac as an organ of nutrition is almost nil in the human embryo, yet it still retains a well-developed blood-supply, the walls of the vesicle, especially, possessing a rich network of vessels. The future history of these vessels, which are known as the vitelline vessels, will be described later on. The Allantois and Belly-stalk.— It has been seen that in reptilian and avian embryos the allantois reaches a high degree of development and functions as a respiratory and excretory organ by coming into contact with what is comparable to the chorion of the mammalian embryo. In man it is very much modified both in its mode of development and in its relations to other parts, so that its resemblance to the avian organ is somewhat obscured. The differences depend partly upon the remarkable abbreviation manifested in the early development of the human embryo and partly upon the fact that the allantois serves to place the embryo in relation with the maternal blood, instead of with the external atmosphere, as is the case in the egg-laying forms. Thus, the THE ALLANTOIS AND BELLY-STALK II7 endodermal portion of the allantois, instead of arising from the intestine and pushing before it a layer of splanchnic mesoderm to form a large sac lying freely in the extra-embryonic portion of the body-cavity, appears in the human embryo before the intes- tine has differentiated from the yolk-sac and pushes its way into the solid mass of mesoderm which forms the belly-stalk (Fig. 66, A). To understand the significance of this process it is neces- sary to recall the abbreviation in the human embryo of the de- velopment of the extra-embryonic mesoderm and body-cavity. Instead of growing out from the embryonic area, as it does in the lower forms, this mesoderm develops in situ from the cellular magma and, furthermore, the extra- embryonic body-cavity arises before there is any trace of a splitting of the embryonic mesoderm (Fig. 39). The belly-stalk, whose development from a portion of the inner cell-mass has already been traced (p. 72), is to be regarded as a portion of the body of "*«''»^5m the embryo, since the ectoderm which ^"°- 67-— Transverse Sec- ■' ' _ TION THROUGH THE BeLLY- covers one surface of it resembles ex- stalk of an Embryo of 2.1s actly that of the embryonic disk and *™' „ ^.,. , , „ ■^ . -^ A a. Umbilical (allantoic) shows an extension backward of the artery; AU, allantois; am, am- medullary groove upon its surface (Fig. "dn'-'ifff^.T''""'' ^"^"*°"^ 67). The mesoderm, therefore, of the belly-stalk is to be regarded as a portion of the embryonic mesoderm which has not yet undergone a splitting into somatic and splanchnic layers, and, indeed, it never does undergo such a splitting, so that there is no body-cavity into which the endo- dermal allantoic diverticulum can grow. But this does not account for all the peculiarities of the human allantois. In the birds, and indeed in the lower oviparous mam- mals, the endodermal portion of the allantois is equally developed with the mesodermal portion, the allantois being an extensive sac whose cavity is filled with fluid, and this is also true of such mam- mals as the marsupials, the rabbit, and the ruminants. In man, Il8 THE ALLANTOIS AND BELLY-STALK however, the endodermal diverticulum never becomes a sac-like structure, but is a slender tube extending from the intestine to the chorion and lying in the substance of the mesoderm of the belly- stalk (Fig. 66, D), the greater portion of which is to be regarded as homologous with the relatively thin layer of splanchnic mesoderm covering the endodermal diverticulum of the chick. An explana- tion of this disparity in the development of the mesodermal and endodermal portions of the human allantois is perhaps to be found in the altered conditions under which the respiration and secretion take place. In all forms, the lower as well as the higher, it is the mesoderm which is the more important constituent of the allantois, since in it the blood-vessels, upon whose presence the physiological functions depend, arise and are embedded. In the birds and oviparous mammals there are no means by which excreted material can be passed to the exterior of the ovum, and it is, therefore, stored up within the cavity of the allantois, the allantoic fluid containing considerable quantities of nitrogen, indi- cating the presence of urea. In the higher mammals the intimate relations which develop between the chorion and the uterine walls allow of the passage of excreted fluids into the maternal blood; and the more intimate these relations, the less necessity there is for an allantoic cavity in which excreted fluid may be stored up. The difference in the development of the cavity in the ruminants, for example, and man depends probably upon the greater intimacy of the union between ovum and uterus in the latter, the arrange- ment for the passage of the excreted material into the maternal blood being so perfect that there is practically no need for the development of an allantoic cavity. The portion of the endodermal diverticulum which is enclosed within the umbilical cord persists until birth in a more or less rudimentary condition, but the intra-embryonic portion extending from the apex of the bladder to the umbilicus becomes converted into a solid cord of fibrous tissue termed the urachus. Occasionally a lumen persists in the urachal portion of the allantois and may open to the exterior at the umbilicus, in which case urine from the bladder may escape at the umbilicus. THE UMBILICAL CORD II9 Since the allantois in the human embryo, as well as in the lower forms, is responsible for respiration and excretion, its blood- vessels are well developed. They are represented in the belly- stalk by two veins and two arteries (Fig. 67), known in human embryology as the umbilical veins and arteries. These extend from the body of the embryo out to the chorion, there branching repeatedly to enter the numerous chorionic villi by which the embryonic tissues are placed in relation with the maternal. The Umbilical Cord. — During the process of closing in of the ventral surface of the embryo a stage is reached in which the embryonic and extra-embryonic portions of the body-cavity are completely separated except for a small area, the umbilicus through which the yolk-stalk passes out (Fig. 66, B). At the edges of this area in front and at the sides the embryon'c ectoderm and somatic mesoderm become continuous with the corresponding layers of the amnion, but posteriorly the line of attachment of the amnion passes up upon the sides of the belly-stalk (Fig. 66, B), so that the whole of the ventral surface of the stalk is entirely un- covered by ectoderm, this layer being limited to its dorsal surface (Fig. 67). In subsequent stages the embryonic ectoderm and somatic mesoderm at the edges of the umbilicus grow out ventrally, carrying with them the line of attachment of the amnion and forming a tube which encloses the proximal part of the yolk- stalk. The ectoderm of the belly-stalk at the same time extend- ing more laterally, the condition represented in Fig. 66, C, is produced, and, these processes continuing, the entire belly-stalk, together with the yolk-stalk, becomes enclosed within a cylindrical cord extending from the ventral surface of the body to the chorion and forming the umbilical cord (Fig. 66, D). From this mode of development it is evident that the cord is, strictly speaking, a portion of the embryo, its surfaces being completely covered by embryonic ectoderm, the amnion being carried during its formation further and further from the umbilicus until finally it is attached around the distal extremity of the cord. In enclosing the yolk-stalk the umbilical cord encloses also a small portion of what was originally the extra-embryonic body I20 THE CHORION ur "ua Uv Fig. 68. — Transverse Sections of the Umbilical Cord of Embryos of (^4) 1.8 cm. and (b) 25 cm. al, Allantois; c, coelom; «o, umbilical artery; uv, umbilical vein; ys, yolk-stalk. THE CHORION 121 cavity surrounding the yolk-stalk. A section of the cord in an early stage of its development (Fig. 68, A) will show a thick mass of mesoderm occupying its dorsal region; this represents the mesoderm of the belly-stalk and contains the allantois and the umbilical arteries and vein (the two veins originally present in the belly-stalk having fused), while toward the ventral surface there will be seen a distinct cavity in which lies the yolk stalk with its accompanying blood-vessels. The portion of this ccelom nearest the body of the embryo becomes much enlarged, and during the second month of development contains some coils of the small intestine, but later the entire cavity becomes more and more encroached upon by the growth of the mesoderm, and at about the fourth month is entirely obliterated. A section of the cord subsequent to that period of development will show a solid mass of mesoderm in which are embedded the umbilical ar- teries and vein, the allantois, and the rudiments of the yolk- stalk (Fig. 68, B). When fully formed, the umbilical cord measures on the aver- age 55 cm. in length, though it varies considerably in different cases, and has a diameter of about 1.5 cm. It presents the ap- pearance of being spirally twisted, an appearance largely due, however, to the spiral course pursued by the umbilical arteries, though the entire cord may undergo a certain amount of torsion from the movements of the embryo in the later stages of develop- ment and may even be knotted. The greater part of its sub- stance is formed by the mesoderm, the cells of which become stellate and form a reticulum, the meshes of which are occupied by connective-tissue fibrils and a mucous fluid which gives to the tissue a jelly-like consistence, whence it has received the name of Wharton's jelly. The Chorion. — To understand the developmental changes which the chorion undergoes it wiU be of advantage to obtain some insight into the manner in which the ovum becomes implanted in the wall of the uterus. Nothing is known as to how this implanta- tion is effected in the case of the human ovum; it has already been accomplished in the youngest ovum at present known. But the 122 IHE CHORION process has been observed in other mammals, and what takes place in Spermophilus, for example, may be supposed to give a clue to what occurs in the human ovum. In the spermophile the ovum lies free in the uterine cavity up to a stage at which the vacuolization of the central cells is almost completed (Fig. 69, A). At one region of the covering layer the cells become thicker and later form a syncytial projection or knob which comes into Fig. 69. — Successive Stages in the Implantation of the Ovum of THE Spermophile. u-, Syncytial knob; fe, inner cell-mass. — (Resjek.) contact with the uterine mucosa (Fig. 69, B), and at the point of contact the mucosa cells undergo degeneration, allowing the knob to come into relation with the deeper tissues of the uterus (Fig. 69, C), the process apparently being one in which the mucosa cells are eroded by the syncytial knob. It seems probable that in the human ovum the process is at first of a similar nature and that as the covering layer cells come into contact with the deeper layes of the uterus, these too are eroded, and, the uterine blood-vessels being included in the THE CHORION 123 s UTTt/ \^ mm//d '^^^j^^jb 1 i Wii f/t/i ^B Pig. 70. — Diagrams Illustrating the Implantation of the Ovum. ac. Amniotic cavitjr; hs, belly-stalk; c{, chorion frondosum; cl, chorion laeve; do, decidua capsularis; ic, inner cell-mass; j~, space surrounding ovum which becomes the intervilloiis space; um, uterine mucosa; i), chorionic villus; ys, yolk-sac. 124 THE CHORION erosion process, an extravasation of blood plasma and corpuscles occurs in the vicinity of the burrowing ovum. In the meantime the ovum has increased considerably in size, its growth in these early stages being especially rapid, and the area of contact consequently increases^in size, entailing continued erosion of the uterine mucosa. At the same time, too, the uterine tissues surrounding the ovum grow up around it, forming at first as it Fig. 71. — Section of an Ovum of i mm. A Section of the Embryo Lies in the Lower Part of the Cavity of the Ovum. D, Decidua; E.U., uterine epithelium; Sch, blood-clot closing the aperture left by the sinking of the ovum into the uterine mucosa. — {From Strakl, after Peters.) were a circular wall (Fig. 70, A), and eventually completely enclose it, forming an envelope known as the decidua capsularis or reflexa. The blood extravasation is now contained within a closed space bounded on the one hand by the uterine tissues and on the other by the wall of the ovum (Fig. 70, B). The youngest known human ova have already reached ap- proximately this stage. Thus, the Peters ovum (Fig. 71) had already sunk deeply into the uterine mucosa, the point of entrance THE CHORION 12 5 being indicated by a gap in the decidua capsularis, closed in this case by a patch of coagulated blood (Sch). Ihe uterine tissues in the immediate vicinity of the ovum were much swollen and apparently somewhat necrotic and their blood-vessels could be seen to communicate with the space between the wall of the ovum and the maternal tissues. This space, however, was con- verted into an irregular network of blood lacunae by anastomosing cords of cells, which arose from the wall of the ovum and ex- tended through the space to the maternal tissues; these cords of cells are represented in Fig. 71 by the darker masses projecting from the wall of the ovum and scattered among the paler blood lacunae. This stage of implantation of the ovum is shown dia- grammatically in Fig. 70, B, where, for simplicity's sake, the cell cords are represented merely as processes radiating from the ovum without reaching the maternal tissues. The cell cprds are derivatives of the trophoblast and are, there fore, of embryonic origin. If examined under a higher magnifica- tion than that shown in Fig. 70 they will be seen to be composed an axial core of cells with distinct outlines, enclosed within a layer of protoplasm which lacks all traces of cell boundaries, although it contains numerous nuclei, being what is termed a syncytium or Plasmodium. The two tissues represent the two layers differen- tiated from the original trophoblast, the cellular one being the cyto-trophoblast and the plasmodial one the plasmodi-trophoblast. The latter is the tissue that comes into contact with the maternal blood contained in the lacunar spaces and with the maternal tissues, in connection with these latter sometimes developing into masses of considerable extent. To the plasmodi-trophoblast may be ascribed the active part in the destruction of the maternal tissues and probably also the absorption of the products of the destruction for the nutrition of the growing ovum. For up to this stage the ovum has been playing the role of a parasite thriving upon the tissues of its host. The food material that the ovum thus obtains may con- veniently be termed the embryotroph and the type of placentation which obtains up to this stage and for some time longer may be 126 THE CHORION termed the embryotrophic type. But even in the Peters t^vum the preparation for another type has begun. In earher stages the cell cords were entirely trophoblastic, but in this ovum (Fig. 71) processes from the chorionic mesoderm may be seen projecting into the bases of the cell cords, and in later stages these processes extend farther and farther into the axis of each cord, the anastomoses of the cords disappear and the cords themselves become converted into branching processes, the chorionic villi, which project from the entire surface of the ovum (Fig. 72) into the Fig. 72. — Entire Ovum Aborted at about the Beginning of the Second Month. XiJ^. — (Grosser.) surrounding space, and are bathed by the maternal blood contained in the surrounding space, which may now be known as the inter- villous space. Toward the maternal surface of the space some masses of the trophoblast still persist, uniting the extremities of certain of the villi to the enclosing uterine wall, such viUi being termed fixation villi to distinguish them from others, which project freely into the intervillous space. Later, when the embryonic blood-vessels develop, those associated with the allantois extend outward into the chorionic mesoderm and thence send branches into each villus. The second type of placentation, the hamotro- THE CHORION ^2^ phic type, is thus established, the fetal blood contained in the vessels of the villi receiving nutrition through the walls of the villi from the maternal blood contained in the intervillous space, and, similarly, transferring waste products to it. At first, as stated above, the villi usually cover the entire surface of the ovum, but later, as the ovum increases in size, those villi which are remote from the attachment of the belly-stalk to the chorion are placed at a disadvantage so far as their blood supply is concerned and gradually disappear, and this process Fig. 73. — Two Villi from the Chorion of an Embryo of 7 mm. continues until, finally, only those villi are retained which are in the immediate region of the belly-stalk (Fig. 70, C), these per- sisting to form the fetal portion of the placenta. By these changes the chorion becomes differentiated into two regions (Fig. 70, C), one of which is destitute of villi and is termed the chorion Iceve, while the other, provided with them, is known as the chorion frondosum. Occasionally one or more patches of villi may persist in the area that normally becomes the chorion Iseve and thus accessory placenta {placenta succenturiata) , vaiying in number and size, may be formed. 128 THE CHORION Pj(- ^^ — Transverse Sections through Chorionic Villi in (A) the Fifth AND (B) THE Seventh Month of Development. cf, Canalized fibrin; Ic, Langhans cells; i, syncytium. — (A which is more highly magnified than B, from Szymonowicz; B from Minot.) THE CHORION 129 The villi when fully formed are processes of the ' chorion, branching profusely and irregularly (Fig. 73) , and each consists of a core of mesoderm, containing blood-vessels, enclosed within a double layer of trophoblastic tissue (Fig. 74, A). The inner layer consists of a sheet of well-defined cells arranged in a single series; it is derived from the cyto-trophoblast and forms what is known as the layer of Langhans cells. The outer layer is syncytial in structure and is formed from the plasmodi-trophoblast. [ Pig. 75. — Mature Placenta after Separation from the uterus. c, Cotyledons; ch, chorion, amnion, and decidua vera; um, umbilical cord. — (,Kollmann.) As development proceeds the villi, which are at first distributed evenly over the chorion frondosum, become separated into groups termed cotyledons (Fig. 75) by the growth into the intervillous space of trabeculae from the walls of the uterus, the fixation villi becoming connected with these septa as well as with the general uterine wall. The ectoderm of the villi undergoes also certain changes with advancing growth, the layer of Langhans cells disappearing except in small areas scattered irregularly in the villi, and the syncytium, though persisting, undergoes local thick- enings which become replaced, 'more or less extensively, by de- positions of fibrin (Fig. 74 B, cf). I30 THE DECIDU^ The changes which occur during the later stages of develop- ment in the chorion are very similar to those described for the villi. Thus, the mesoderm thickens, its outermost layers be- coming exceedingly fibrillar in structure, while later, as in the villi, the syncytial layer of its trophoblast is replaced in irregu- Jte L"^ •«*&>' •»• ■^S' P^v TTTHS Fig. 76. — Section through the Placental Chorion of an Embryo of Seven Months. c, Cell layer; e-p, remnants of epithelium; fb, fibrin layer; mes, mesoderm. — (Minot.) lar patches by a peculiar form of fibrin which is traversed by flattened anastomosing spaces and to which the name canalized fibrin ox fibrinoid has been applied (Fig. 76). The Deciduae. — It has been pointed out (p. 27) that in connec- tion with the phenomenon of menstruation periodic alterations THE DECIDU^ 131 occur in the mucous membrane of the uterus. If during one of these periods a fertilized ovum reaches the uterus, the desquama- tion of portions of the epithehum does not occur nor is there any appreciable hemorrhage into the cavity of the uterus ; the uterine mucosa remains in what is practically the ante-menstrual condi- tion until the conclusion of pregnancy, when, after the birth of the fetus, a considerable portion of its thickness is expelled from Fig. 77. — Diagram showing the relations of the Petal Membranes. Am, Amnion; Ch, chorion; M, muscular wall of uterus; C, decidua capsularis; B, decidua basalis; V, decidua vera; Y, yolk-stall:. the uterus, forming what is termed the decidua. In other words, the sloughing of the uterine tissue which concludes the process of menstruation is postponed until the close of pregnancy, and then takes place simultaneously over the whole extent of the uterus. Of course, the changes in the uterine tissues are somewhat more extensive during pregnancy than during menstruation, but there is an undoubted fundamental similarity in the changes during the two processes. 132 THE DECIDU^ The human ovum comes into direct apposition with only a small portion of the uterine wall, and the changes which this portion of the wall undergoes differ somewhat from those occur- ring elsewhere. Consequently it becomes possible to divide the deciduae into (i) a portion which is not in direct contact with the ovum, the decidua vera (Fig. 77, V) and (2) a portion which is. The latter portion is again capable of division. The ovum be- FiG. 78. — Surface view of Half of the Decidua Vera at the End of the Third Week of Gestation. d, Mucous membrane of the Fallopian tubes; ds, prolongation of the vera toward the cervix uteri; pp., papillas; rf, marginal furrow. (Kollmann.) comes completely embedded in the mucosa, but, as has been pointed out, the chorionic vilh reach their full development only over that portion of the chorion to which the belly-stalk is at- tached. The decidua which is in relation to this chorion frondo- sum undergoes much more extensive modifications than that in relation to the chorion laeve, and to it the name of decidua basalts {decidua serotina) (Fig. 77, 5) is applied, while the rest of the de- THE DECIDUA VERA ^33 cidua which encloses the ovum is termed the decidua capsularis (decidua reflexa) (C). The changes which give rise to the decidua vera may first be described and those occurring in the others considered in succession. (a) Decidua vera. — On opening a uterus during the fourth or fifth month of pregnancy, when the decidua vera is at the height of its development, the surface of the mucosa presents a corrugated appearance and is traversed by irregular and rather deep grooves CFig. 78). This appearance ceases at the internal orifice, the mucous membrane of the cervix uteri not forming a decidua, and the deciduae of the two surfaces of the uterus are separated by a distinct furrow known as the marginal groove. In sections the mucosa is found to have become greatly thickened, frequently meas- uring I cm. in thickness, and its glands have undergone very considerable modifica- tion. Normally almost straight (Fig. 79, A), they increase in length, not only keeping Fig. 79. — Diagrammatic Sections of the Uterine Mucosa, A, in the Non- pregnant Uterus, and B, at the Beginning of Pregnancy. c. Stratum compactum; gl, the deepest portions of the glands; m, muscular layer; sp, stratum spongiosum. — {Kundrat and Englemann.) pace with the thickening of the mucosa, but surpassing its growth, so that they become very much contorted and are, in addition, considerably dilated (Fig. 79, B). Near their mouths they are dilated, but not very much contorted, while lower down the reverse 134 THE DECIDUA CAPSULARIS is the case, and it is possible to recognize three layers in the de- cidua, (i) a stratum compactum nearest the lumen of the uterus, containing the straight but dilated portions of the glands; (2) a stratum spongiosum, so called from the appearance which it presents in sections owing to the dilated and contorted portions of the glands being cut in various planes; and (3) next the mus- cular coat of the uterus a layer containing the contorted but not dilated extremities of the glands is found. Only in the last layer does the epithelium of the glands retain its normal columnar form ; elsewhere the cells, separated from the walls of the glands, become enlarged and irregular in shape and eventually degenerate. In addition to these changes, the epithelium of the mucosa disappears completely during the first month of pregnancy, and the tissue between the glands in the stratum compactum becomes packed with large, often multinucleated cells, which are termed the decidual cells and are probably derived from the connective tissue cells of the mucosa. After the end of the fifth month the increasing size of the embryo and its membranes exerts a certain amount of pressure on the decidua, and it begins to diminish in thickness. The portions of the glands which lie in the stratum compactum become more and more compressed and finally disappear, while in the spongi- osum the spaces become much flattened and the vascularity of the whole decidua, at first so pronounced, diminishes greatly. (b) Decidua capsularis. — The decidua capsularis has also been termed the decidua reflexa, on the supposition that it was formed as a fold of the uterine mucosa reflected over the ovum after this had attached itself to the uterine wall. Since, however, the attachment of the ovum is to be regarded as a process of burrowing into the uterine tissues (see p. 122), the necessity for an upgrowth of a fold is limited to an elevation of the uterine tissues in the neighborhood of the ovum to keep pace with its increasing size. Since it is part of the area of contact with the ovum it possesses no epithelium upon the surface turned toward the ovum, although in the earlier stages its outer surface is covered by an epithehum continuous with that of the decidua vera , and between it and the THE DECIDUA BASALIS 135 chorion there is a portion of the blood extravasation in which the villi formed from the chorion Iseve float. Glands and blood-vessels also occur in its walls in the earlier stages of development. As the ovum continues to increase in size the capsularis begins to show signs of degeneration, these appearing first over the pole of the ovum opposite the point of fixation. Here, even in the case of the ovum described by Rossi Doria, the cavity of which measured 6X5 mm. in diameter, it has become reduced to a thin membrane destitute of either Blood-vessels or glands, and the degeneration gradually extends throughout the entire capsule, the portion of the blood space whic^h it encloses also disappearing. At about the fifth month the growth of thie ovum has brought the capsularis in contact throughout its whole extent with the vera, and it then appears as a whitish transparent membrane with no trace of either glands or blood-vessels, and it eventually disappears by fusing with the vera. (c) Decidua basalis. — ^The structure of the decidua basalis, also known as the decidua serotina, is practically the same as that of the vera up to about the fifth month. It differs only in that, being part of the area of contact of the ovum, it loses its epithelium much earlier and is also the seat of extensive blood extravasations, due to the erosion of its vessels by the chorionic trophoblast. Its glands, however, undergo the same changes as those of the vera, so that in it also a compactum and a spongiosum may be recog- nized. Beyond the fifth month, however, there is a great differ- ence between it and the vera, in that, being concerned with the nutrition of the embryo, it does not partake of the degeneration noticeable in the other deciduae, but persists until birth, forming a part of the structure termed the placenta. The Placenta. — This organ, which forms the connection be- tween the embryo and the maternal tissues, is composed of two parts, separated by the intervillous space. One of these parts is of embryonic origin, being the chorion frondosum, while the other belongs to the maternal tissues and is the decidua basalis. Hence the terms placenta fetalis and placenta uterina frequently applied to the two parts. The fully formed placenta is a more 136 THE PLACENIA or less discoidal structure, convex on the surface next the uterine muscularis and concave on that turned toward the embryo, the umbilical cord being continuous with it near the center of the latter surface. It averages about 3.5 cm. in thickness, thinning out somewhat toward the edges, and has a diameter of 15 to 20 cm., and a weight varying between 500 and 1250 grams. It is situated on one of the surfaces of the uterus, the posterior more frequently than the anterior, and usually much nearer the fundus than the internal orifice. It develops, in fact, wherever the ovum happens to become attached to the uterine walls, and occasionally this attachment is not accomplished until the ovum has descended nearly to the internal orifice, in which case the placenta may com- pletely "close this opening and form what is termed a placenta pravia. If a section of a placenta in a somewhat advanced stage of de- velopment be made, the following structures may be distinguished: On the inner surface there will be a delicate layer representing the amnion (Fig. 80, Am), and next to this a somewhat thicker one which is the chorion (Cho), in which the degenerative changes al- ready mentioned may be observed. Succeeding this comes a much broader area composed of the large intervillous blood space in which lie sections of the villi (vi) cut in various directions. Then follows the stratum compactum of the basalis, next the stratum spongiosum (£>')> next the outermost l^yer of the mucosa (D"), in which the uterine glands retain their epithelium, and, filially the muscularis uteri (Mc). These various structures have, for the most part, been already described and it remains here only to say a few words concerning the special structure of the basal compactum and concerning certain changes that take place in the intervillous space. The stratum compactum of the basal decidua forms what is termed the basal plate of the placenta, closing the intervillous space on the uterine side and being traversed by the maternal blood- vessels that open into the space. Tie formation of canalized fibrin, already mentioned in connection with the decidua vera and the syncytium of the villi, also occurs in the basal portion of the THE PLACENTA 137 m Pig. 80. — Section through a Placenta of Seven Months' Development. Am, Amnion; cho, chorion; D, layer of decidua containing the uterine glands; Mc, m-' — '" """'■ "* *'"' "tsr'is: Ve. maternal blood-vessel; Vi, stalk of a villus; vi, villi in 138 S N V) V THE PLACENTA ■«3 > 01 S * •2-5 O u-c 3 ° B ft 3-2 < y H Z H U <; z <; X go ^5'^ ™ --* *. ■J3 ■> ^ to .. . ^ +3 "S* O P* h. 10 " 8 g-ii •s 'it » ft ■PC" ft m " ft* J3 o 00 -^ P ,; S ° t^ a" o .M = C8 u SEPARATION OF THE DECIDUiE I39 decidua, a definite layer of it, known as Nitabuch's fibrin stria, being a characteristic constituent of the basal plate and patches of greater or less extent also occur upon the surface of the plate. Leucocytes also occur in considerable abundance in the plate and their presence has been taken to indicate an attempt on the part of the maternal tissues to resist the erosive action of the parasitic ovum. From the surface of the basal plate processes, termed placental septa, project into the intervillous space, group- ing the villi into cotyledons and giving attachment to some of the fixation villi (Fig. 81). Throughout the greater extent of the placenta the septa do not reach the surface of the chorion, but at the periphery, throughout a narrow zone, they do come into contact with the chorion and unite beneath it to form a membrane which has been termed the closing plate. Beneath this lies the peripheral portion of the intervillous space, which, ow'ng to the arrangement of the septa in this region, appears to be imperfectly separated from the rest of the space and forms what is termed the marginal sinus (Fig. 81). Attention has already been called to the formation of canalized fibrin or fibrinoid in connection with the syncytium of the villi. In the later stages of pregnancy there may be produced by this process masses of fibrinoid of considerable size, lying in the inter- villous space; these, on account of their color, are termed white infarcts and may frequently be observed as whitish or grayish patches through the walls of the placenta after its expulsion. Red infarcts produced by the clotting of the blood, also occur, but with much less regularity and frequency. The Separation of the Deciduae at Birth. — At parturition, after the rupture of the amnion and the expulsion of the fetus, there still remain in the uterine cavity the deciduae and the amnion, which is in contact but not fused with the deciduae. A continu- ance of the uterine contractions, producing what are termed the "after-pains," results in the separation of the placenta from the uterine walls, the separation taking place in the deep layers of the spongiosum, so that the portion of the mucosum which contains the undegenerated glands remains behind. As soon as the I40 SEPARATION OF THE DECIDU^ placenta has separated, the separation of the decidua vera takes place gradually though rapidly, the line of separation again being in the deeper layers of the stratum spongiosum, and the whole of the deciduae, together with the amnion, is expelled from the uterus forming what is known as the "after-birth." Hemorrhage from the uterine vessels during and after the separation of the deciduae is prevented by the contractions of the uterine walls, assisted, according to some authors, by a pre- liminary blocking of the mouths of the uterine vessels by certain large polynuclear decidual cells found during the later months of pregnancy in the outer layers of the decidua basalis. The re- generation of the uterine mucosa after parturition has its start- ing-point from the epithelium of the undegenerated glands which persist, this epithelium rapidly evolving a complete mucosa over the entire surface of the uterus. The complicated arrangement of the human placenta is, of course, the culmination of a long series of speciaUzations, the path along which these have proceeded being probably indicated by the conditions ob- taining in some of the lower mammals. The Monotremes resemble the reptiles in being oviparous and in this group of forms there is no relation of the ovum to the maternal tissues such as occurs in the formation of a placenta. In the other mammals viviparity is the rule and this condition does demand some sort of connection between the fetal and maternal tissues. One of the simplest of such con- nections is that seen in the pig, where the chorionic viUi of the ovum fit into corresponding depressions in the uterine mucosa, this tissue, however, undergoing no destruction, and at birth the vilU simply withdraw from the depressions of the mucosa, leaving it intact. This type of placentation is an embryotrophic one, and since there is no separation of deciduae from the uterine wall after pregnancy it is also of the indeciduate type. In the sheep the placentation is also embryo- trophic and indeciduate, but destruction of the maternal mucosa does take place, the villi penetrating deeply into it and coming into rela- tion with the connective tissue surrounding the maternal blood-vessels. Another step in advance is shown by the dog, in which even the connective tissue around the maternal vessels in the placental area undergoes almost complete destruction so that the chorionic villi are separated from the maternal blood practically only by the endothelial lining of the maternal vessels. In this case the mucosa undergoes so much alteration that the undestroyed portions of it are sloughed off after birth as a decidua, so that the placentation, like that in man, is LITERATURE I41 of the deciduate type. It still represents, however, an embryotrophic type, although closely approximating to the hsemotrophic one found in man, in which, as described above, the destruction of the maternal tissues proceeds so far as to open into the maternal blood-vessels, so that the fetal villi are in direct contact with the maternal blood. If these various stages may be taken to represent steps by which the conditions obtaining in the human placenta have been evolved, the entire process may be regarded as the result of a progressive activity of a parasitic ovum. In the simplest stage the pabulum supplied by the uterus was sufficient for the nutrition of the parasite, but gradu- ally the ovum, by means of its plasmodi-trophoblast, began to attack the tissues of its host, thus obtaining increased jiutrition, until finally, breaking through into the maternal blood-vessels, it achieved for itself still more favorable nutrition, by coming into direct contact with the maternal blood. LITERATURE In addition to the papers by Beneke and Strahl, Bryce and Teacher, Frassi, Jung, Herzog, Grosser and Linzenmeier cited in Chapter III, the following may be mentioned : A. Branca: "Recherches sur la structure, devolution et le r61e de la vesicule om- bilicale de I'homme" Journ. de I'Anat. el de la Physiol., XLix, 1913. E.Cova: "Ueber ein menschliches Ei der zweiten 'Woche,"4rcA. fur Gynaek., ixxxiii, 1907. A. Debeyre: "Description d'un embryon humain de 0.9 mm.," Journ. de I'Anat. el de la Physiol, xLviii, 1912. L. Frassi: "Ueber ein junges menschliches Ei in situ," Arch, fiir mikr. Anal., lxx, 1907. O. Grosser: "Vergleichende Anatomie und Entwicklungsgeschichte der Eihaute und der Placenta mit besonderer Berucksichtigung des Menschen," Wien, 1909. H. Happe: "Beobachtungen an Eihauten junger menschlicher Eier," Anal. Hefte, xxxn, 1906. W. His: "Die Umschliessung der menschlichen Frucht wahrend der fruhesten Zeit des Schwangerschafts," Archivfiir Anal, und Physiol., Anal. Abth., 1897. M. Hofmeier: "Die menschliche Placenta," Wiesbaden, 1890. R. W. Johnstone: "Contribution to the study of the early human ovum," Journ. Obslet. and Gynaek., xxvi, 1914. F. Keibel: "Zur Entwickelungsgeschichte der Placenta," Anal. Anzeiger, iv, 1889. F. Keibel: "Ueber die Grenze zwischen miitterlichen und fetalen Gewebe," Anal. Anzeiger, XLVm, 1915. J. Kollmann: "Die menschlichen Eier von 6 mm. Grosse," Archivfiir Anal, und Physiol., Anal. Abth., 1879. T. G. Lee: "Implantation of the ovum in Spermophilus tridecemlineatus Mitch." Mark Anniversary Volume, New York, 1904. G. Leopold: "Ueber ein sehr junges menschliches Ei in situ," Arb. aus der konigl. FrauenkUnik in Dresden, rv, 1906. 142 LITERATURE F. Marchand: " Beobachtungen an jungen menschlichen Eiern," Anai. Hefle, xxi, 1903. J. Merttens: "Beitrage zur normalen und pathologischen Anatomie der mensch- lichen Placenta," Zeitschrift fur Geburtshiilfe und GynaekoL, xxx and xxxi, 1894. C. S. Minot: "Uterus and Embryo," Journal of MorphoL, 11, 1889. G. Pai.adino: "Sur la gen^se des espaces intervilleux du placenta humain et de leur premier contenu, comparativement 6. la mgme partie chez quelques mammiferes, Archives Ital. de Biolog., xxxi and xxxn, 1899. H. Peters: "Ueber die Einbettung des menschlichen Eies und das fruheste bisher bekannte menschliche Placentationsstadium," Leipzig und Wien, 1899. J. Rejsek: "Anheftung (Implantation) des Saiigetiereies an die Uteruswand, insbe- sondere des Eies von Spermophilus cAfShii," Arch, fiir mikrosk. Anat., Lxm, 1904. T. Rossi Doria: "Ueber die Einbettung des menschlichen Eies, studirt an einem kleinen Eie der zweiten Woche," Arch, fur Gynaek., lxxvi, 1905. C. Rtjge: "Ueber die menschliche Placentation," Zeitschrift fur Geburtshiilfe und Gynaekol, xxxix, 1898. Siegenbeek VAN Heukelom: "Ueber die menschliche Placentation," Arch. f. Anal. und Phys., Anat. Abth., 1898. F. Graf Spee: "Ueber die menschliche Eikammer und Becidua reflexa," Verhandl. des Anat. Gesellsch., xii, 1898. H. Strahl: "Die menschliche Placenta," Ergtbn. der Anat. und Entwickl., 11, 1893. " Neues iiber den Bau der Placenta," ibid, vi, 1897. "Placentaranatomie," iftid., VIII, 1899. R. ToDYO: "Ein junges menschliches Ei," Arch, fiir Gynaek., xcv, 1912. Van Cauwenberghe: "Recherches sur la r61e du Syncytium dans la nutrition embryonnaire de la femme," Arch, de Biol., xxiii, 1907. J. C. Webster: "Human Placentation," Chicago, 1901. E. Wormser: "Die Regeneration der Uterusschleimhaut nach der Geburt," Arch. fiir Gynaek., Lxrx, 1903. PART II ORGANOGENY CHAPTER VI THE DEVELOPMENT OF THE INTEGUMENTARY SYSTEM The Development of the Skin. — The skin is composed of two embryologically distinct portions, the outer epidermal layer being developed from the ectoderm, while the dermal layer is mesen- chymatous in its origin. The ectoderm covering the general surface of the body is, in the earliest stages of development, a single layer of cells, but at the end of the first month it is composed of two layers, an outer one, the epitrichium, consisting of slightly flattened cells, and a lower one whose cells are larger, and which will give rise to the epidermis (Fig. 82, A). During the second month the differences between the two layers become more pronounced, the epitrichial cells assuming a characteristic domed form and becoming vesicular in structure (Fig. 82, B). These cells persist until about the sixth month of development, but after that they are cast off, and, becoming mixed with the secretion of sebaceous glands which have appeared by this time, form a constituent of the vernix caseosa. In the meantime changes have been taking place in the epi- dermal layer which result in its becoming several layers thick (Fig. 82, E), the innermost layer being composed of cells rich in protoplasm, while those of the outer layers are irregular in shape and have clearer contents. As development proceeds the number of layers increases and the superficial ones, undergoing a horny degeneration, give rise to the stratum corneum, while the deeper 14.^ 144 DEVELOPMENT OF THE SKIN ones become the stratum Malpighii. At about the fourth month ridges develop on the under surface of the epidermis, projecting downward into the dermis, and later secondary ridges appear in the intervals between the primary ones, while on the palms and soles ridges appear upon the outer surface of the epidermis, corre- sponding in position to the primary ridges of the under surface. The mesenchyme which gives rise to the dermis grows in from all sides between the epidermis and the outer layer of the myo- tomes, which are at first in contact, and forms a continuous layer Fig. 82. — A, Section of Skin from the Dorsum of Finger of an Embryo of 4.5 CM, B, from the Plantar Surface of the Foot of an Embryo of 10.2 cm. et, Epitrichium ; ep, epidermis. underlying the epidermis and showing no indications of a seg- mental arrangement. It becomes converted principally into fibrous connective tissue, the outer layers of which are relatively compact, while the deeper ones are looser, forming the subcu- taneous areolar tissue. Some of the mesenchymal cells, how- ever, become converted into non-striated muscle-fibers, which for the most part are few in number and associated with the hair follicles, though in certain regions, such as the skin of the scrotum, they are very numerous and form a distinct layer known as the dartos. Some cells also arrange themselves in groups and undergo DEVELOPMENT OF THE NAILS I4S a fatty degeneration, well-defined masses of adipose tissue embedded in the lower layers of the dermis being thus formed at^about the sixth month. Although the dermal mesenchyme is unseg- mental in character, yet the nerves which send branches to it are segmental, and it might be expected that indications of this condition would be retained by the cutaneous nerves even in the adult. A study of the cutaneous nerve-supply in the adult realizes to a very considerable extent this expectation, the areas supplied by the vari- ous nerves forming more or less distinct zones, and being therefore segmental (Fig. 83). But a considerable commingling of adjacent areas has also occurred. Thus, while the distribution of the cutaneous branches of the fourth thoracic nerve,as determined experimentally in the monkey (Macacus), is distinctly zonal or segmental, the nipple lying practically in the middle line of the zone, the upper half of its area is also supplied or overlapped by fibers of the third nerve and the lower half by fibers of the fifth (Fig. 84), so that any area of skin in the zone is innervated by fibers coming from at least two segmental nerves (Sherrington). And, furthermore, the distribu- tion of each nerve crosses the mid-ventral line of the body, forming a more or less extensive crossed overlap. And not only is there a confusion of adjacent areas but an area may shift its position relatively to the deeper structures supplied by the same nerve, so that the skin over a certain muscle is not necessarily supplied by fibers from the nerve which supplied the muscle. Thus, in the lower half of the abdomen, the skin at any point will be supplied by fibers from higher nerves than those supplying the underlying muscles (Sherrington), and the skin of the limbs may receive twigs from nerves which are not represented at all in the muscle-supply (second and third thoracic and third sacral). The Development of the Nails. — The earliest indications of the development of the 10 7/ 'fi rj] TV rs Te TT Ta Tio Tii^ JTri Lt Is St Fig. 83. — Diagram showing the cuta- NEOUS Distribution OF THE Spinal Nerves. —{Head.) 146 DEVELOPMENT OF THE NAILS nails have been described by Zander in embryos of about nine weeks as slight thickenings of the epidermis of the tips of the digits, these thickenings being separated from the neigh- boring tissue by a faint groove. Later the nail areas migrate Fig. 84. — Diagram showing the Overlap of the ///, IV, and V Intercostal Nerves of a Monkey. — {Sherrington.) Fig. 85. — Longitudinal Section through the Terminal Joint of the Index- finger OF AN Embryo of 4.5 cm. < e. Epidermis; ep, epitrichium; «/, nail fold; Ph, terminal phalanx; sp, sole plate. to the dorsal surfaces of the terminal phalanges (Fig. 85) and the grooves surrounding the areas deepen, especially at their proximal edges, where they form the nail-folds (nf), while distally thickenings of the epidermis occur to form what have been termed DEVELOPMENT OF THE NAILS 147 SPA sc ep- nb sole-plates (sp), structures quite rudimentary in man, but largely developed in the lower animals, in which they form a considerable portion of the claws. The actual nail substance does not form, however, until the embryo has reached a length of about 17 cm. By this time the epidermis has become several layers thick and its outer layers, over the nail areas as well as elsewhere, have become transformed into the stratum corneum (Fig. 86, sc), and it is in the deep layers of this (the stratum lucidum) that keratin granules develop in cells wh'ch degenerate to g've rise to the nail substance (n). At its first formation, accordingly the nail is covered by the outer layers of the stratum corneum as well as by the epitrichium, the two together forming what has been termed the eponychium (Fig. 86, ep) . The epitrichium soon disappears, how- ever, leaving only the outer layers of the stratum corneum as a covering, and this also later dis- appears with the exception of a narrow band surrounding the base of the nail which persists as the perionyx. The formation of the nail begins in the more proximal portion of the nail area and its further growth is by the addition of new keratinized cells to its proximal edge and lower surface, these cells being formed only in the proximal part of the nail bed in a region marked by its whitish color and termed the lunula. ^■^ The first appearance of the nail areas at the tips of the digits as described by Zander has not yet been confirmed by later observers, but the migra- tion of the areas to the dorsal surfaces necessitated by such a location of the primary differentiation affords an explanation of the otherwise anomal us cutaneous nerve-supply of the nail areas in the adult, this being from the palmar (plantar) nerves. Fig. 86. — ^Longi- tudinal Section THROUGH THE NaIL Area in an Embryo OF 17 CM. ep, Eponychium; n, nail substance ; nb, nail bed; sc, stratum corneum; sp, sole plate. — (Okamura.') 148 DEVELOPMENT OF THE HAIRS The Development of the Hairs. — The hairs begin to develop at about the third month and continue to be formed during the remaining portions of fetal Ufe. They arise as solid cylindrical downgrowths, projecting obliquely into the subjacent dermis from the lower surface of the epidermis. As these downgrowths con- tinue to elongate, they assume a somewhat club-shaped form (Fig. 87, A), and later the extremity of each club moulds itself Til -~: Fig. 87. — The Development of a Hair. c. Cylindrical cells of stratum mucosum; hf, wall of hair follicle; m, mesoderm; mu, stratum mucosum of epidermis; -p, hair papilla; r, root of hair; 5, sebaceous gland. — (KoHma»».) over the summit of a small papilla which develops from the dermis (Fig. 87, B). Even before the dermal papilla has made its appearance, however, a differentiation of the cells of the down- growth becomes evident, the central cells becoming at first spindle- shaped and then undergoing a keratinization to form the hair shaft, while the more peripheral ones assume a cuboidal form and DEVELOPMENT OF THE HAIRS 1 49 constitute the lining of the hair follicle. The further growth of the hair takes place by the addition to its basal portion of new keratinized cells, probably produced Ijy the multiplication of the epidermal cells which envelop the papilla. From the cells which form the lining of each follicle an out- growth takes place into the surrounding dermis to form a se- baceous gland, which is at first solid and club-shaped, though later it becomes lobed. The central cells of the outgrowth separate from the peripheral and from one another, and, their protoplasm undergoing a fatty degeneration, they finally pass out into the space between the follicle walls and the hair and so reach the surface, the peripheral cells later giving rise by division to new generations of central cells. During fetal life the fatty material thus poured out upon the surface of the body becomes mingled with the cast-off epitrichial cells and constitutes the white oleaginous substance, the vernix caseosa, which covers the surface of the new-born child. The muscles, arrectores pilorum, coimected with the hair follicles arise from the mesenchyme cells of the surrounding dermis. The first growth of hair forms a dense covering over the entire surface of the fetus, the hairs which compose it being exceedingly fine and silky and constituting what is termed the lanugo. This growth is cast off soon after birth, except over .the face, where it is hardly noticeable on account of its extreme fineness and lack of coloration. The coarser hairs which replace it in certain regions of the body probably arise from new follicles, since the formation of follicles takes place throughout the later periods of fetal life and possibly after birth. But even these later formed hairs do not individually persist for any great length of time, but are con- tinually being shed, new or secondary hairs normally developing in their places. The shedding of a hair is preceded by a cessation of the proliferation of the cells covering the dermal papilla and by a shrinkage of the papilla, whereby it becomes detached from the hair, and the replacing hair arises from a papilla which is prob- ably budded off from the older one before its degeneration and carries with it a cap of epidermal cells. ISO DEVELOPMENT OF THE SUDORIPAROUS GLANDS It is uncertain whether the cases of excessive development of hair over the face and upper part of the body which occasionally occur are due to an excessive development of the later hair follicles (hyper- trichosis) or to a persistence ^nd continued growth of the lanugo. The Development of the Sudoriparous Glands. — The sudori- parous glands arise during the fifth month as solid cylindrical outgrowths from the primary ridges of the epidermis (Fig. 88), and at first project vertically downward into the subjacent dermis. Later, however, the lower end of each downgrowth is thrown into coils, and at the same time a lumen appears in the center. Since, however, the cylinders are formed from the deeper layers of the epidermis, their lumina do not at first open upon the surface, but gradually approach it as the cells of the deeper layers of the epidermis replace those which are continually being cast off from the surface of the stratum corneum. The final opening to the surface occurs during the seventh month of development. The Development of the Mammary Glands. — In the ma- jority of the lower mammals a number of mammary glands occur, arranged in two longitudinal rows, and it has been observed that in the pig the first indication of their development is seen in a thickening of the epidermis along a line situated at the junction of the abdominal walls with the membrana reuniens (Schulze). This thickening subsequently becomes a pronounced ridge, the milk ridge, from which, at certain points, the mammary glands develop, the ridge disappearing in the intervals. In human embryos 8 mm. or less in length a similar epidermal thickening has been observed extending from just below the axilla to the inguinal region (Fig. 89). Later, in embryos of 10 to 13 mm., the anterior part of the thickening becomes more distinct while its lower two-thirds become less distinct and eventually disappear. Fig. 88.^ — ^LoWER Surface of a De- tached Portion of Epidermis from THE Dorsum of the Hand. h, Hair follicle: x, sudoriparous gland. — (Blaschko.) DEVELOPMENT OF THE MAMMARY GLANDS 151 In somewhat older embryos (14 to 18 mm.) the gland is rep- resented by a marked thickening of the epidermis which projects down into the dermis and has a circular outline (Fig. 90, A). Later the thickening becomes lobed (Fig. 90, B), and its superficial and central cells become cornified and are cast off, so that the gland area appears as a depression of the surface of the skin. During the fifth and sixth months the lobes elongate into solid cylindrical columns of cells (Fig. 91) resembling not a little the cylinders which become con- verted into sudoriparous glands, and each column becomes slightly enlarged at its lower end, from wt ich outgrowths be- gin to develop to form the acini. A lumen first appears in the lower ends of the col- umns and is formed by the separation and breaking down of the central cells, the peri- pheral cells persisting as the lining of the acini and ducts. The elevation of the gland Fig. 89. — Milk ridge (,mr) in a Human i_ .1 r i r Embryo. — (Kallius.) area above the surface to form the nipple appears to occur at different periods in different embryos and frequently does not take place until after birth. In the re- gion aroimd the nipple sudoriparous and sebaceous glands develop, the latter also occurring within the nipple area and fre- quently opening into the extremities of the lacteal ducts. In the areola, as the area surrounding the nipple is termed, other glands known as Montgomery's glands, also appear, their development resembling that of the mammary gland so closely as to render it probable that they are really rudimentary mammary glands, perhaps developments of portions of the original milk ridge other than that which gives rise to the main gland. The further development of the glands, consisting of an in- crease in the length of the ducts and the development from them of 152 DEVELOPMENT OF THE MAMMARY GLANDS additional acini, continues slowly up to the time of puberty in both sexes, but at that period further growth usually ceases in the male, while in females it continues for a time and the subjacent dermal tissues, especially the adipose tissue, undergo a rapid development. The occurrence of a milk ridge in human embryos is of special inter- est in connection with the occasional formation of supernumerary Pig. 90. — Sections through the Epidermal Thickenings which Represent THE Mammary Gland in Embryos {A) of 6 cm. and {B) of 10.2 cm. mammary glands (polymastia). This is by no means an infrequent anomaly; it has been observed in 19 per cent, of over 100,000 soldiers of the German army and in 47 per cent, of the individuals of certain regions of Germany. The anomalous glands may appear anywhere along the line of the original milk ridge, though they are occasionally found elsewhere, as, for instance, on the inner surface of the thigh. They also vary greatly in their development, their presence being fre- quently indicated merely by a nipple-like elevation (hyper thelia). Such accessory nipples sometimes occur in the areolar area of an other- wise normal gland and in such cases may represent an hypertrophy of one or more of Montgomery's glands. LITERATURE IS3 It is stated that a slight and temporary enlargement of the gland occurs at each premenstrual period, but if pregnancy supervenes marked enlargement occurs and a certain amount of secretion is formed, this, however, not being true milk, but a watery fluid, rich in proteids and known as colostrum. It is only after, parturition that the secre- tion of milk begins, apparently standing in some relation to the expul- sion of the fetus. It was formerly supposed that the correlation of the activity of the mammary glands with uterine conditions was dependent upon some nervous connection, but this has been shown to be fallacious and it seems more probable that the stimulus which excites the gland is chemical in its nature. There is experimental evidence that indicates Fig. gi. — Section through the Mammary Gland of an Embryo of 25 cm. I, Stroma of the gland. — (Prom Nagel, after Basch.) that the growth of the gland during pregnancy is due to a hormone produced in the tissues of the embryo and fetus, this hormone inhibiting milk secretion, while it stimulates the growth of the gland, and on the explusion of the fetus, the cause or the inhibition being removed, the hypertrophied gland starts to function. Although the glands are nor- mally functional only in females, cases are not unknown in which they have become well developed and functional in males (gynwcomasHa) . Furthermore, a functional activity of the glands normally occurs im- mediately after birth, infants of both sexes yielding a few drops of a milky fluid, the so-called witch-milk (Hexenmilch), when the glands are subjected to pressure. LITERATURE R. Bonnet: "Die Mammarorgane im Lichte der Ontogenie und Phylogenie," Ergebn. Anat. und Entwick., 11, 1892; vn, 1898. J. T. Bowen: "The Epitrichial Layer of the Human Epidermis,'' Anat. Anzeiger, IV, 1889. Brouha: "Recherches sur les diverses phases du d^veloppement et de I'activitfi de la mammelle," Arch, de Biol., xxi, 1905. G. Burckhard: "Ueber embryonale Hj^iermastie und Hyperthelie," Anat. Hefte, vni, 1897. 154 LITERATURE H. Eggeling: "Ueber ein wichtiges Stadium in der Entwicklumgsgeschichte der menschlichen BrustdrUse," Anaf. Anzeiger, xxiv, i8g6. H. Head: "On Disturbances of Senssition with Special Reference to the Pain of Visceral Disease," Brain, xvi, 1892; xvn, 1894; andxrx, 1896. E. Kallius: "Ein Fall von Milchleiste bei einem menschlichen Embryo," Anal. Hefte, vni, 1897. J. E. Lane-Claypon and E. S. Starling: "An Experimental inquiry into the factors which determine the growth and activity of the mammary glands," Proc. Roy. Soc. Londdn, Ser. B., lxxvii, igo6. Hilda Lustig: "Zur Entwicklungsgeschichte der menschlichen BrustdrUse." Arch, fiir mikr. AnaL, Lxxxvn, 1915. T. Okamura: "Ueber die Entwicklung des Nagels beim Menschen," Archh fiir Dermatol, und Syphilol., xxv, 1900. H. Schmidt: "Ueber normale Hyperthelie menschlicher Embryonen und iiber die erste Anlage der menschlichen Milchdriisen uberhaupt," Morphol. Arbeiten, XVII, 1897. O. ScHULTz: "Ueber die erste Anlage des milchdrusen Apparates.'' Anat. An- zeiger, Vin, 1892. C. S. Sherrington: "Experiments in Examination of the Peripheral Distribution of the Fibres of the Posterior Roots of some Spinal Nerves," Philos. Trans. Royal, Soc, CLXxxiv, 1893, and cxc, 1898. P. Stohr: " Entwickelungsgeschichte des menschlichen WoUhaares," Anat. Hefte. XXIII, 1903. M. Strahl: "Die erste Entwicklung der Mammarorgane beim Menschen," Verhandl. Anal. Gesellsch., xn, i8g8. R. Zander: "Die fruhesten Stadien der Nagelentwicklung und ihre Beziehungen zu den Digitalnerven, Arch, fiir Anat: und Physiol., Anat. Abth., 1884. CHAPTER VII THE DEVELOPMENT OF THE CONNECTIVE TISSUES AND SKELETON It has been seen that the cells of a very considerable portion of the somatic and splanchnic mesoderm, as well as of parts of the mesodermic somites, become converted into mesenchyme. A very considerable portion of this becomes converted into what are termed connective or supporting tissues, characterized by con- sisting of a non-cellular matrix in which more or less scattered cells are embedded. These tissues enter to a greater or less extent into the formation of all the organs of the body, with the exception of those forming the central nervous system, and constitute a network, which holds together and supports the elements of which the organs are composed; in addition, they take the form of definite membranes (serous membranes, fasciae), cords (tendons, ligaments), or solid masses (cartilage), or form looser masses or layers of a somewhat spongy texture (areolar tissue) . The inter- mediate substance is somewhat varied in character, being com- posed sometimes of white, non-branching, non-elastic fibers; some- times of yellow, branching, elastic fibers; of white, branching, but inelastic fibers which form a reticuliun; or of a soft gelatinous substance containing considerable quantities of mucin, as in the tissue which constitutes the Whartonian jelly of the umbilical cord. Again, in cartilage the matrix is compact and homo- geneous, or, in other cases, more or less fibrous, passing over into ordinary fibrous tissue, and, finally, in bone the organic matrix is largely impregnated with salts of lime. Two views exist as to the mode of formation of the matrix, some authors maintaining that in the fibrous tissues it is produced by the actual transformation of the mesenchyme cells into fibers, while others claim that it is manufactured by the cells but does not 156 DEVELOPMENT OF CONNECTIVE TISSUE directly represent the cells themselves. Fibrils and material out of which fibrils could be formed have undoubtedly been observed in connective-tissue cells, but whether or not these are later passed to the exterior of the cell to form a connective-tissue fiber is not yet certain, and on this hangs mainly the difference between the theories. \\ Recently it has been held (Mall) that the mesenchyme of the embryo is really a syncytium in and from the protoplasm_of which Fig. 92. — Portion of the Center of Ossification of the Parietal Bone of a Human Embryo. the matrix forms; if this be correct, the distinction which the older views make between the intercellular and intracellular origin of the matrix becomes of little importance. Bone differs from the other varieties of connective tissue in that it is never a primary formation, but is always developed either in fibrous tissue or cartilage; and according as it is associated with the one or the other, it is spoken of as membrane hone or cartilage hone. In the development of membrane bone some of the con- nective-tissue cells, which in consequence become known as osteo- blasts, deposit lime salts in the matrix in the form of bony spicules which increase in size and soon unite to form a network (Fig. 92). The trabeculae of the network continue to thicken, while, at the same time, the formation of spicules extends further out into the coimective-tissue membrane, radiating in all directions from the region in which it first developed. Later the connective DEVELOPMENT OF BONE 157 tissue which hes upon either surface of the reticular plate of bone thus produced condenses to form a stout membrane, the periosteum, between which and the osseous plate osteoclasts arrange themselves in a more or less definite layer and deposit upon the surface of the plate a lamella of compact bone. A membrane bone, such as one of the flat bones of the skull, thus comes to be composed of two plates of compact bone, the inner and outer tables, enclosing and united to a middle plate of spongy bone which constitutes the diploe. With bones formed from car- tilage the process is somewhat different. In the center of the cartilage the intercellular matrix becomes increased so that the cells appear to be more scattered and a calcareous deposit forms in it. All aroxmd this region of calcification the cells arrange themselves in rows (Fig. 93) and the process of calcification ex- tends into the trabeculae of mat- Pig. 93. — Longitudinal Section OF rix which separate these rows, phalanx of a Pinger of an Embryo While these processes have been o^sM months. c. Cartilage trabeculEe; p, periosteal takmg place the mesenchyme bone; po, periosteum; *, ossification surrounding the cartUage has be- '=enter.-(5.ymo»o«,i..,) Come converted into a periosteum (po), similar to that of membrane bone, and its osteoclasts deposit a layer of bone (p) upon the sur- face of the cartilage. The cartilage cells now disappear from the intervals between the trabeculae of calcified matrix, which form a fine network into which masses of mesenchyme (Fig. 94 pi), containing blood-vessels and osteoclasts, here and there penetrate from the periosteum, after having broken through the layer of periosteal bone. These masses absorb a portion of the fine calcified network and so transform it into a coarse network, the ?S8 DEVELOPMENT OF BONE cc P' meshes of which they occupy to form the hone marrow (m), and the osteoclasts which they contain arrange themselves on the surface of the persisting trabeculae and deposit layers of bone upon their surfaces. In the meantime the calcification of the cartilage matrix has been extending, and as fast as the network of calcified tra- beculae is formed it is invaded by the mesenchyme, imtil finally the cartilage becomes entirely con- verted into a mass of spongy bone enclosed within a layer of more compact periosteal bone. As a rule, each cartilage bone is developed from a single center of ossification, and when it is found that a bone of the skull, for instance, develops by several centers, it is to be regarded as formed by the fusion of several primarily distinct bones, a con- clusion which may generally be confirmed by a comparison of the bone in question with its homo- logues in the lower vertebrates. Exceptions to this rule occur in bones situated in the median line of the body, these occasionally developing from two centers lying one on either side of the median line, but such centers are usually to be regarded as a double center rather than as two distinct centers, and are merely an expression of the fundamental bilater- ality which exists even in median structures. More striking exceptions are to be found in the long bones in which one or both extremities develop from special centers which give rise to the epiphyses (Fig. 95, ep, ep'), the shaft or diaphysis (d) being formed from the primary center. Similar secondary centers appear in marked prominences on bones to which power- ful muscles are attached (Fig. 95, a and b), but these, as well as Pig. 94. — The Ossification Center OF Fig. 92 More Highly Magnified. c. Ossifying trabeculae ; cc, cavity of cartilage network; m, marrow cells; p, periosteal bone; pi, irruption of peri- osteal tissue; po, periosteum. — Szymo- nowicz.) DEVELOPMENT OF B01»rE 159 the epiphysial centers, can readily be recognized as secondary from the fact that they do not appear until much later than the primary centers of the hones to which they belong. These sec- ondary centers give the necessary firmness required for articular surfaces and for the attachment of muscles and, at the same time, make provision for the growth in length of the bone, since a plate of cartilage always intervenes between the epi- physes and the diaphysis. This cartilage con- tinues to be transformed into bone on both its surfaces by the extension of both the epiphysial and diaphysial ossification into it, and, at the same time, it grows in thickness with equal rapidity until the bone reaches its required length, whereupon the rapidity of the growth of the cartilage diminishes and it gradually becomes completely ossified, unit- ing together the epiphysis and diaphysis. The growth in thickness of the long bones is, however, an entirely different process, and is due to the formation of new layers of periosteal bone on the outside of those already present. But in connection with this process an absorption of bone also takes place. A section through the middle of the shaft of a humerus, for example, at an early stage of development would show a peri- pheral zone of compact bone surrounding a core of spongy bone, the meshes of the latter being occupied by the marrow tissue. A similar section of an adult bone, on the other hand, would show only the peripheral compact bone, much thicker than before and enclosing a large marrow cavity in which no trace of spongy bone might remain. The difference depends on the fact that as the periosteal bone increases in thickness, there is a gradual absorp- tion of the spongy bone and also of the earlier layers of periosteal Fig. 95. — The Ossi- fication Centers of THE Femur. a, and b. Secondary centers for the great and lesser trochanters; d, diaphysis; ep, upper and ep', lower epiphysis. — (Testut.) l6o DEVELOPMENT OF BONE bone, this absorption being carried on by large multinucleated cells, termed osteoclasts, derived from the marrow mesenchyme. By their action the bone is enabled to reach its requisite diameter and strength, without becoming an almost solid and unwieldy mass of compact bone. It has recently been claimed (Arey) that the evidence showing that the osteoclasts are the effective agents in bone absorption is entirely inadequate. Instead of being active structures they are held to be produced by the fusion of degenerate and worn-out osteoclasts. Fig. 96. — A, Transverse Section of the Femur of a Pig Killed after Having been fed with Madder for Four Weeks; B, the Same of a Pig Killed Two Months after the Cessation of the Madder Feeding. The heavy black line represents the portion of bone stained by the madder. — (After Flourens.) During the ossification of the cartilaginous trabeculae osteo- clasts become enclosed by the bony substance, the cavities in which they lie forming the lacuncB and processes radiating out from them, the canaliculi, so characteristic of bone tissue. In the growth of periosteal bone not only do osteoclasts become enclosed, but blood-vessels also, the Haversian canals being formed in this way, and lamellae of bone are deposited around these by the enclosed osteoclasts to form Haversian systems. That the absorption of periosteal bone takes place during growth can be demonstrated by taking advantage of the fact that the coloring substance madder, when consumed with food, tinges the bone being formed at the time a distinct red. In pigs fed with madder for a time and theii killed a section of the femur shows a superficial band of red bone (Fig. 96. .4), but if the animals be allowed to live for one or two months after the cessation of the madder feeding, the red band will be found to be covered by a layer of white bone varying in thickness DEVELOPMENT OF THE SKELETON l6l according to the interval elapsed since the cessation of feeding (Fig. 96 B) ; and if this interval amount to four months, it will be found that the thickness of the uncolored bone between the red bone and the marrow cavity will have greatly diminshed (Flourens). The Development of the Skeleton.— Embryologically con- sidered, the skeleton is composed of two portions, the axial skeleton Pig. 97. — Frontal Section through Mesodermic Somites of a Calf Embryo. isa. Intersegmental artery; my, myotome; «, central nervous system; nc, notochord; sea and scp, anterior and posterior portions of sclerotomes. consisting of the skull, the vertebrae, ribs, and sternum, developing from the sclerotomes of the mesodermal somites, and the appen- dicular skeleton, which includes the pectoral and pelvic girdles and the bones of the limbs, and which arises from themesench3ane of the somatic mesoderm. It will be convenient to consider first the development of the axial skeleton, and of this the differen- tiation of the vertebral column and ribs may first be discussed. l62 DEVELOPMENT OF THE VERTEBS.iS The Development of the Vertebrae and Ribs.— The mesen- chyme formed from the sclerotome of each mesodermic somite grows inward toward the median line and forms a mass lying between the notochord and the myotome, separated from the similar mass in front and behind by some loose tissue in which Ues an intersegmental artery. Toward the end of the third week of development the cells of the posterior portion of each sclerotome condense to a tissue more compact than that of the anterior portion (Fig. 97), and a little later the two portions become separated by a cleft. At about the same time the posterior por- tion sends a process medially, to enclose the notochord by uniting with a corresponding process from the sclerotome of the other side and it also sends a prolong- ation dorsally between the myo- tome and the spinal cord to form the vertebral arch, and a third process laterally and ventrally along the distal border of the myotome to form a costal process (Fig. 98). The looser tissue of the anterior half of the sclerotome also grows medially to surround the noto- chord, filling up the intervals between successive denser portions, and it forms too a membrane extending between successive verte- bral arches. Later that tissue surrounding the notochord which is derived from the anterior half of the sclerotome, associates itself with the posterior portion of the preceding sclerotome to form what will later be a vertebra, the tissue occupying and adjacent to the line of division between the anterior and posterior por- tions of the sclerotomes condensing to form intervertebral fibro- cartilages. Consequently each vertebra is formed by parts from two sclerotomes, the original intersegmental artery passes over Fig. 98. — Transverse Section through the intervertebral plate OF THE First Cervical Vertebra of A Calf Embryo of 8.8 mm. bc^. Intervertebral plate; m*, fourth myotome; s, hypochordal bar; XI, spinal accessory nerve. — {Froriep.) DEVELOPMENT OF THE VERTEBRAE 163 the body of a vertebra, and the vertebrae themselves alternate with the myotomes (Fig. 99). With this differentiation the first or blastemic stage of the development of the vertebrae closes. In the second or cartilaginous stage, portions of the sclero- tomic mesenchyme become transformed into cartilage. In the posterior portion of each vertebral body, that is to say in the portion formed from the anterior halves of the more posterior of the two pairs of sclerotomes entering into its formation, two centers of chondr'fication appear, one on each side of the median VntSig Met Sou Pig. 99. — Diagram to show the Relation of the Vertebr/E to the Meso- DERMic Somites. ID, Intervetebral disk; LS, ligamentum flavuni; NA, neural arch, V, vertebra line, and these eventually unite to form a single cartilaginous body, the chondrification probably also extending to some extent into the denser anterior portion of the body. A center also appears in each half of the vertebral arch and in each costal process, the cartilages formed in the costal processes of the anterior cervical region uniting across the median line below the notochord, to form what has been termed a hypochordal bar (Figs. 98 and 100) . These bars are for the most part but transitory, recalling structures 164 DEVELOPMENT OP THE VERTEBRAE occurring in the lower vertebrates; in the mammalia they de- generate before the close of the cartilaginous stage of development, except in the case of the atlas, whose development will be de- scribed later. As development proceeds the cartilages of the vertebral arches and costal processes increase in length and come into contact with the cartilaginous bodies, with which they eventually fuse, aiid from the vertebral arches processes grow out which represent the future transverse and articular processes. The fusion of the cartilage of the costal process with the body of the vertebra does not, however, persist. Later a solution of the junction occurs and the process becomes a rib cartilage, the mesen- chyme surrounding the area of solution forming the costo-vertebral ligaments. At first the rib cartilage is separated by a distinct interval from the transverse process of the vertebral arch, but later it develops a process, the tubercle, which bridges the gap and forms an articulation with the transverse process. The mesenchyme which extends between successive vertebral arches does not chondrify, but later becomes transformed into the interspinous ligaments and the ligamenta flava, while the anterior and posterior longitudinal ligaments are formed from unchondri- fied portions of the tissue surrounding the vertebral bodies. As was pointed out, the mesenchyme in the region of the cleft separating the anterior and posterior portions of a sclerotome be- comes an intervertebral fibrocartilage, and, as the cartilaginous bodies develop, the portions of the notochord enclosed by them become constricted, while at the same time the portions in the intervertebral regions increase in size. Finally the notochord dis- appears from the vertebral regions, although a canal, represent- ing its former position, traverses each body for a considerable time, but in the intervertebral regions it persists as relatively large flat disks forming the pulpy nuclei of the fibrocartilages. The mode of development described above applies to the great majority of the vertebrae, but some departures from it occur, and these may be conveniently considered before passing on to an account of the ossification of the cartilages. The variations affect principally the extremes of the series. Thus the posterior verte- DEVELOPMENT OF THE VERTEBRAE i6S brae present a reduction of the vertebral arches, those of the last sacral vertebrae being but feebly developed, while in the coccygeal vertebrae they are indicated only in the first. In the first cervical vertebra, the atlas, the reverse is the case, for the entire adult vertebra is formed from the posterior portion of a sclerotome, its lateral masses and posterior arch being the vertebral arches, while its anterior arch is the hypochordal bar, which persists in this Pig. 100. — Longitudinal Section through the Occipital Region and Upper Cervical Vertebrae of a Calf Embryo of i8.s mm. bas. Basilar artery; ch, 'notochord; Kc^~*, vertebral centra; lc''~*, intervertebral disks; occ, basioccipital ; Sc^~^, hypochordal bars. — (Froriep.) vertebra only. A well-developed centrum is also formed, however (Fig. loo), but it does not unite with the parts derived from the preceding sclerotome, but during its ossification unites with the centrum of the epistropheus (axis), forming the odontoid process of that vertebra. The epistropheus consequently is formed by one and a haK sclerotomes, while but half a one constitutes the atlas. The extent to which the ribs are developed in connection with 1 66 DEVELOPMENT OF THE VERTEBRAE the various vertebrae also varies considerably. Throughout the cervical region they are short, the upper five or six being no longer than the transverse processes, with the tips" of which their extremities unite at an early stage. In the upper five or six vertebras a relatively large interval persists between the rib and the transverse process, forming the costo-transverse foramen, through which the vertebral vessels pass, but in the seventh verte- bra the fusion is more extensive and the foramen is very small and hardly noticeable. In the thoracic region the ribs reach their greatest development, the upper eight or nine extending almost to the mid-ventral line, where their extremities unite with a longitudinal cartilaginous bar from which the sternum develops (see p. i68). The lower three or four thoracic ribs are success- ively shorter, however, and lead to the condition found in the lumbar vertebrae, where they are again greatly reduced and firmly united with the transverse processes, the union being so close that only the tips of the latter can be distinguished, forming what are known as the accessory tubercles. In the sacral region the ribs are reduced to short flat plates, which unite together to form the lateral masses of the sacrum, and, finally, in the coccygeal re- gion the blastemic costal processes of the first vertebra imite with the transverse processes to form the transverse processes of the adult vertebra, but no indications of them are to be found in the other vertebrae beyond the blastemic stage. The third stage in the development of the axial skeleton begins with the ossification of the cartilages, and in each vertebra there are typically as many primary centers of ossification as there were originally cartilages. Thus, to take a thoracic vertebra as a type, a center appears in each half of each vertebral arch at the base of the transverse process and gradually extends to form the bony lamina, pedicle, and the greater portion of the transverse and spinous processes; a single center gives rise to the body of the vertebra; and each rib ossifies from a single center. These various centers appear early in embryonic life, but the complete transformation of the cartilages into bone does not occur until some time after birth, each vertebra at that period consisting of DEVELOPMENT OF THE VERTEBRiE 1 67 three parts, a body and two halves of an arch, separated by unos- sified cartilage (Fig. loi, A). At about puberty secondary centers make their appearance; one appears in the cartilage which still covers the anterior and posterior surfaces of the vertebral body, producing disks of bone in these situations (Fig. loi, B, en and et), another appears at the tip of each spinous and transverse process (Fig. loi, B), and in the lumbar vertebrae others appear at the tips of the articulating processes. The epiphyses so formed remain separate until growth is completed and between the sixteenth and twenty-fifth years unite with the bones formed from the primary centers, which have fused by this time to form a single vertebra. Each rib ossifies from a single primary center situated near the angle, secondary centers appearing for the capitulum and tuberosity. Fig. ioi. — A, A Vertebra at Birth; B, Lumbar Vertebra showing Secondary Centers of Ossification. a. Center for the articular process; t, body; el, lower epiphysial plate; en, upper epiphysial plate; na, vertebral arch; s, center for spinous process; t, center for trans- verse process. — (JSappey.) In some of the vertebras modifications of this tj^pical mode of ossification occur. Thus, in the upper five cervical vertebrae the centers for the rudimentary ribs are suppressed, ossification ex- tending into them from the vertebral arch centers, and a similar suppression of the costal centers occurs in the lower lumbar verte- brae, the first only developing a separate rib center. Furthermore, in the atlas a double center appears in the persisting hypochordal bar, and the body which corresponds to the atlas, after developing the terminal epiphysial disks, fuses with the body of the epis- tropheus (axis) to form its odontoid process, this vertebra conse- quently possessing, in addition to the typical centers, one (double) 1 68 DEVELOPMENT OF THE STERNUM other primary and two secondary centers. In the sacral region the typical centers appear in all five vertebras, with the exception of rib centers for the last one or two (Fig. 102) , and two additional secondary centers give rise to plate-like epiphyses on each side, the upper plates forming the articular surface for the ilium. At about the twenty-fifth year all the sacral vertebrae unite to form a single bone, and a similar fusion occurs also in the rudimentary vertebrae of the coccyx. The majority of the anomalies seen in the vertebral column are due to the imperfect development of one or more cartilages or of the centers of ossification. Thus, a failure of an arch to unite with the body or Fig. 102. — A, Upper Surface of the First Sacral Vertebra, and B, Ventral View of the Sacrum showing Primary Centers of Ossification. t;, Body; na, vertebral arch; r, rib center. — {Sappey.) even the complete absence of an arch or half an arch may occur, and in cases of spina bifida the two halves of the arches fail to unite dorsally. Occasionally the two parts of the double cartilaginous center for the body fail to unite, a double body resulting; or one of the two parts may entirely fail, the result being the formation of only one-half of the body of the vertebra. Other anomaUes result from the excessive development of parts. Thus, the rib of the seventh cervical vertebra may sometines remain distinct and be almost long enough to reach the sternum, and the first lumbar rib may also fail to unite with its vertebra. On the other hand, the first thoracic rib is occasionally found to be imperfect. The Development of the Sternmn.— Longitudinal cartilagin- ous bars, with which the ventral end„s of the anterior eight or DEVELOPMENT OF THE STERNUM 169 nine cartilaginous thoracic ribs unite, represent the future sternum. At an early period the two bars come into contact anteriorly and fuse together (Fig. 103), and at this anterior end two usually indistinctly separated masses of cartilage are to be observed at the vicinity of the points where the ventral ends of the carti- laginous clavicles articulate. These are the episternal cartilages {em), which later normally unite with the longitudinal bars and Fig. 103. — Formation of the Sternum in an Embryo of about 3 cm. el. Clavicle; em, episternal cartilage. — (Ruge.) form part of the manubrium sterni, though occasionally they persistand ossify to form the ossa suprasternalia. The fusion of the longitudinal bars gradually extends backward until a single elongated plate of cartilage results, with which the seven anterior ribs are united, one or two of the more posterior ribs which originally were connected with each bar having separated. The portions of the bars separated from these posterior ribs con- stitute the xiphoid process. The ossification of the sternum (Fig. 104) partakes to a certain 170 DEVELOPMENT OF THE STERNUM extent of the original bilateral origin of the cartilage, but also shows marked indications of a segmental arrangement, the centers tending to correspond with the ribs that unite with the sternum. In the portion of the cartilage which lies below the junction of the third costal cartilages a series of two or more pairs of centers appears just about birth, each pair being situated opposite an intercostal space. Later the centers of each pair fuse and the single centers so formed, extending through the cartilage, eventu- ally unite to form the greater part of the body of the bone. Pig. 104. — Sternum of New-born Child, showing Centers of Ossification. / to VII, Costal cartilages. — (Gegenbaur.) Fig. 105. — Reconstruction of the Chondro- CRANIUM of an EmBRYO OF 14 MM. as, Alisphenoid; bo, basioccipital; bs, basi- sphenoid; eo, exoccipital; ra, Meckel's cartilage; OS, orbitosphenoid; p, periotic; ps, presphenoid; so, sella turcia; s, supraoccipital. — {Levi.) Above the attachment of the third ribs, however, two single centers appear, the lower of which unites with the more posterior centers to form the upper part of the body, while the uppermost center gives rise to the manubrium, which frequently persists as a distinct bone united to the body by a hinge-joint. It has been generally supposed that the longitudinal cartilaginous bars were formed by the fusion of the upturned ventral ends of the first eight ribs, so that each of the sternal segments (sternebrae) might be regarded as the fused ventral epiphyses of a pair of ribs. Recent observations on pig embryos indicate, however, that the cartilaginous DEVELOPMENT OF THE SKtJLL 171 bars are formed independently of the ribs (Hanson), these latter unit- ing with them only after they are formed. The segmental arrange- ment of the ossification centres seems, nevertheless, to be determined by the association of the ribs with the bars. A failure of the cartilaginous bars to fuse produces the condition known as cleft sternum, or if the failure to fuse affects only a portion of the bars there results a perforated sternum. A perforation or notch- ing of the xiphoid cartilage is of frequent occurrence owing to this being the region where the fusion of the bars takes place last. The suprasternal bones are the rudiments of a bone or cartilage, the omosternum, situated in front of the manubrium in many of the lower mammalia. It furnishes the articular surfaces for the clavicles and is possibly formed by a fusion of the ventral ends of the cartilages which represent those bones; hence its appearance as a pair of bones in the rudimentary condition. The Development of the Skull. — In its earliest stages the human skull is represented by a continuous mass of mesenchyme which invests the anterior portion of the notochord and extends forward beyond its extremity into the nasal region, forming a core for the nasal process (see p. loi). From each side of this basal mass a wing projects dorsally to enclose the anterior portion of the medullary canal which will later become the cerebral part of the central nervous system. No indications of a segmental origin are to be found in this mesenchyme ; as stated, it is a con- tinuous mass, and this is likewise true of the cartilage which later develops in it. The chondrification occurs first along the median line in what will be the occipital and sphenoidal regions of the skull (Fig. 105) and thence gradually extends forward into the ethmoidal region and to a certain extent dorsally at the sides and behind into the regions later occupied by the wings of the sphenoid {as and os) and the squamous portion of the occipital (5). No cartilage de- velops, however, in the rest of the sides or in the roof of the skull, but the mesenchyme of these regions becomes converted into a dense membrane of connective tissue. While the chondrifica- tion is proceeding in the regions mentioned, the mesenchyme which encloses the internal ear becomes converted into cartilage, form- ing a mass, the periotic capsule (Fig. 105, p), wedged in on either side between the occipital and sphenoidal regions, with which it 172 DEVELOPMENT OF THE SKULL eventually unites to form a continuous chondrocranium, perfo- rated by foramina for the passage of nerves and vessels. . , _ The posterior part of the basilar portion of the occipital cartilage presents certain pecu- liarities of development. In calf embryos there are in this region, in very early stages, four separate condensations of mesoderm cor- responding to as manymesodermic somites and to the three roots of the hypoglossal nerve together with the first cervical or subocci- pital nerve (Froriep) (Fig. 106). These mesenchymal masses in their general characters and rela- tions resemble vertebral bodies, and there are good reasons for believing that they represent four vertebrae which, in later stages, are taken -up into the skull re- gion and fuse with the primitive chondrocranium. In the human embryo they are less distinct than in lower mammals, but since a three-rooted hypoglossal and suboccipital nerve also occur in THROUGH THE OCCIPITAL AND UPPER j^^n it IS probablc that the cor- Cervical Regions of a Calf Em- _ ^ BRYo OF 8.7 MM. rcspondlng vertebrae are also rep- ai and ai'. Intervertebral arteries; rgsentcd. Indeed, Confirmation ic', first cervical intervertebral plate; _ _ ' bo suboccipital intervertebral plate; of their existence may be found in T:::^^i c":ruii;t.ro°cSi the fact that during the cartilag- myotomes; m«-', cervical myotomes; JnoUS Stage Of the skuU the hypo- o'-', roots of hypoglossal nerve; >3. , , , . ,..,,. jugular vein; x and xi, vagus and glossal toramma are divided into spinal accessory ntrv^s.-(Froriep.) ^^^^^ portions by two Cartilaginous partitions which separates the three roots of the hypoglossal nerve. Fig. 106. — Frontal Section DEVELOPMENT OF THE SKULL 173 It seems certain from the evidence derived from embryology and comparative anatomy that the human skull is composed of a primitive unsegmental chondrocranium plus four vertebrae, the latter being added to and incorporated with the occipital portion of the chondrocranium. Emphasis must be laid upon the fact that the cartilaginous portion of the skull forms only the base and lower portions of the sides of the cranium, its entire roof, as well as the face region, showing no indication of cartilage, the mesenchjone in these regions being converted into fibrous connective tissue, which, especially in the cranial region, assumes the form of a dense membrane. But in addition to the chondrocranium and the ver- tebrae incorporated with it, other cartilaginous elements enter into the composition of the skull. The mesenchyme which occupies the axis of each branchial arch undergoes more or less complete chon- drification, cartilaginous bars being so formed, certain of which enter into very close relations with the skull. It has been seen (p. 94) that each half of the first arch gives rise to a maxillary process which grows forward and ventrally to form the anterior boimdary of the mouth, while the remaining portion of the arch forms the mandibular process. The whole of the axis of the mandibular process becomes chondrified, forming a rod known as Meckel's cartilage, and this, at its dorsal end, comes into relation with the periotic capsule, as does also the dorsal end of the carti- lage of the second arch. In the remaining three arches cartilage forms only in the ventral portions, so that their rods do not come into relation with the skull, though it will be convenient to consider their further history together with that of the other branchial arch Fig. 107. — Diagram showing the Five Branchial Cartilages, 7 to V. Al, Atlas; Ax, epistropheus; 3, third cervical vertebra. 174 DEVELOPMENT OF THE SKULL cartilages. The arrangement of these cartilages is shown dia- grammatically in Fig. 107. By the ossification of these various parts three categories of bones are formed: (i) cartilage bones formed in the chondrocranium, (2) membrane bones, and (3) cartilage bones developing from the cartilages of the branchial arches. The bones belonging to each of these categories are primarily quite distinct from one another and from those of the other groups, but in the human skull a, very considerable amount of fusion of the primary bones takes place, and elements belonging to two or even to all three categories may unite to form a single bone of the adult skull. In a certain region of the chondrocranimn also and in one of the branchial arches the original cartilage bone becomes ensheathed by membrane bone and eventually disappears com- pletely, so that the adult bone, Pig. 108.— OccipT^aTbone of a Fetus although represented by a carti- AT Term. lagg^ jg really a membrane bone. bo, Basioccipital : eo, exoccipital: ip, a j • j j ai • i interparietal; so. supraoccipitai. And, mdeed, this process has pro- ceeded so far in certain portions of the branchial arch skeleton that the original cartilaginous representatives are no longer developed, but the bones are deposited directly in connective tissue. These various modi- fications interfere greatly with the precise application to the human skull of the classification of bones into the three categories given above, and indeed the true significance of certain of the skull bones can only be perceived by comparative studies. Nevertheless it seems advisable to retain the classification, indicat- ing, where necessary, the confusion of bones of the various categories. OSSIFICATION OF THE CHONDROCRANIUM 1 75 The Ossification of the Chondrocranium. — The ossification of the cartilage of the occipital region results in the formation of four distinct bones which even at birth are separated from one another by bands of cartilage. The portion of cartilage lying in front of the foramen magnum ossifies to form a basioccipital bone (Fig. 108, bo) , the portions on either side of this give rise to the two exoccipiials (eo), which bear the condyles, and the por- tion above the foramen produces a supraoccipital (so), which repre- sents the part of the squamous portion of the adult bone lying below the superior nuchal line. All that portion of the bone which lies above that line is composed of membrane bone which Fig. 109. — Sphenoid Bone from Embryo of 3H to 4 Months. The parts which are still cartilaginous are represented in black, as, AUsphe- noid; b, basisphenoid ; I, lingula; os, orbitosphenoid; p, internal pterygoid plate. — {Sappey.) owes its origin to the fusion of two or sometimes four centers of ossification, appearing in the membranous roof of the embryonic skull. The bone so formed (ip) represents the interparietal of lower vertebrates and, at an early stage, unites with the supra- occipital, although even at birth an indication of the line of union of the two parts is to be seen in two deep incisions at the sides of the bone. The union of the exoccipitals and supraoccipital takes place in the course of the first or second year after birth, but the basioccipital does not fuse with the rest of the bone until the sixth or eighth year. It will be noticed that no special centers occur for the four occipital vertebrae, these structures having become completely incorporated in the chondrocranium, and even the cartilaginous partitions which divide the hypoglossal foramina usually disappear during the process of ossification. 176 OSSIFICATION or THE CHONDROCRANITJM Two pairs of centers have been described for the interparietal bone and it has been claimed that the deep lateral incisions divide the lower pair, so that when the incisions meet and persist as the sutura mendosa, separating the so-called inca hone from the rest of the occipital, the division does not correspond to the line between the supraoccipital and the interparietal, but a portion of the latter bone remains in connection with the supraoccipital. Mall, how- ever, in twenty preparations, found but a single pair of centers for the interparietal. Occasionally an additional pair of small centers appear for the uppermost angle of the interparietal, and the bones formed from them may remain distinct as what have been termed fontanelle bones. In the sphenoidal region the number of distinct bones which develop is much greater than in the occipital region. At the be- ginning of the second month a center appears in each of the carti- lages which represent the alisphenoids (great wings) . These cartilages do not, however, represent the entire extent of the great wings and their ossification gives rise only to those portions of the bone in the neighborhood of the foramina ovale and rotundum and to the lateral pterygoid plates. The remaining portions of the wings, the orbital and temporal portions, develop as mem- brane bone (Fawcett) and early unite with the portions formed from the cartilage. At the end of the second month a center a.ppea.Tsmea,ch.orbitosphenoid (lesser wing) cartilage (Fig. 109, os), and a little later a pair of centers (6), placed side by side, are developed in the cartilage representing the posterior portion of the body; together these form what is known as the basisphenoid. Still later a center appears on either side of the basisphenoids to form the Hngulce (/), and another pair appears in the anterior part of the cartilage, between theorbitosphenoids, and represent the presphenoid. In addition to these ten centers in cartilage and the membrane portion of the alisphenoid, two other membrane bones are included in the adult sphenoid. Thus, a little before the appearance of the center for the alisphenoids an ossification is formed in the mesen- chyme of each lateral wall of the posterior part of the nasal cavity and gives rise to the medial lamina of the pterygoid process, the mesenchyme at the tip of the ossification condensing to form a OSSIFICATION OF THE CHONDROCRANIUM 177 cartilaginous hook-like structure over which the tendon of the tensor veli palatini plays. This cartilage later ossifies to form the pterygoid hamulus, the medial pterygoid lamina being thus a combination of membrane and cartilage bone, the latter, however, being a secondary development and quite independent of the chondrocranium . By the sixth month the lingulae have fused with the basi- sphenoid and the orbitosphenoids with the presphenoid, and a little later the basisphenoid and presphenoid unite. The ali- sphenoids and medial pterygoid -lam- inae remain separate, however, until after birth, fusing with the remaining portions of the adult bone during the first year. The cartilage of the ethmoidal region of the chondrocranium forms somewhat later than the other por- tions and consists at first of a stout median mass projecting downward and forward into the nasal process (Fig. (Im), situated one on either side in the mesenchyme on the outer side of each olfactory pit. Ossification of the lateral masses or ectethmoids begins relatively early, but it appears in the upper part of the median cartilage only after birth, pro- ducing the crista galli and the perpendicular plate, which together form what is termed the mesethmoid. When first formed, the three cartilages are quite separate from one another, the olfactory and nasal nerves passing down between them to the olfactory pit, but later trabecule begin to extend across from the mesethmoid to the upper part of the ectethmoids and eventually form a fenestrated horizontal lamella which ossifies to form the cribriform plate. The lower part of the median cartilage does not ossify, but a center appears on each side of the median line in the mesenchyme behind and below its posterior or lower border. From these Fig. iio. — Anterior Por- tion OF THE Base of the Skull OF A 6 TO 7 Months' Embryo. The shaded parts represent IIO, Ip), and two lateral masses cartilage, cp. Cribriform plate; Im, lateral mass of the ethmoid; Ip, perpendicular plate; of, optic foramen; os, orbitosphenoid. — (After von Spec.) 178 OSSIFICATION OF THE CHONDROCRANIUM centers two vertical bony plates develop which unite by their median surfaces below, and above invest the lower border of the cartilage and form the vomer. The portion of the cartilage which is thus invested undergoes resorption, but the more anterior portions persist to form the cartilaginous septum of the nose. The vomer, consequently, is not really a portion of the chondro- cranium, but is a membrane bone ; its intimate relations with the median ethmoidal cartilage, however, make it convenient to consider it in this place. When first formed, the ectethmoids are masses of spongy bone and show no indication of the honeycombed appear- ance which they present in the adult skull. This condition is produced by the absorption of the bone of each mass by evaginations into it of the mucous membrane lining the nasal cavity. This same process also brings about the for- mation of the curved plates of bone which project from the inner surfaces of the lateral masses and are known as the superior and middle conchae (turbinated bones). The inferior and sphenoidal conchae are developed from special centers, but belong to the same category as the others, being formed from portions of the lateral ethmoidal cartilages which become almost separated at an early stage before the ossification has made much progress. Absorption of the body of the sphenoid bone to form the sphenoidal cells, of the frontal to form the frontal sinuses, and of the maxillaries to form the maxillary antra is also produced by outgrowths of the nasal mucous membrane, all these cavities, as well as the ethmoidal cells, being continuous with the nasal cavities and lined with an epithelium which is continuous with the mucous membrane of the nose. In the lower mammalia the erosion of the mesial surface of the ectethmoidal cartilages results, as a rule, in the formation of five con- / Fig. III. — The Temporal Bone at Birth. The Styloid Process and Auditory Ossi- cles ARE NOT Represented. 'p. Petrous bone; s, squamosal; /, tympanic. — {Poirier.) OSSIFICATION OF THE CHONDROCRANIUM 1 79 chae, while in man but three are usually recognized. Not infrequently, however, indications of an additional concha above what is ordinarily termed the superior concha is observed in man, and in front of the superior concha a slight elevation, termed the agger nasi, is always observable and its lower edge is prolonged downwards and backwards to form what is termed the uncinate process of the ethmoid. This proc- ess and the agger together represent another concha of the typical mam- malian arrangement, to which, therefore, the human arrangement may be reduced. A number of dienters of ossification — the exact number is yet uncertain — appear in the periotic capsule during the later portions of the fifth month, and during the sixth month these unite together to form a single center from which the complete ossification of the cartilage proceeds to form the petrous and mastoid portions of the temporal bone (Fig. in, ^). The mastoid process does not really form until several years after birth, being produced by the hollow- ing and bulging out of a portion of the petrous bone by outgrowths from the lining membrane of the middle ear. The cavities so formed are the mastoid cells, and their relations to the middle-ear cavity are in all respects similar to those of the ethmoidal and sphenoidal cells to the nasal cavities. The remaining portions of the temporal bone are partly formed by membrane bone and partly from the branchial arch skeleton. An ossification appears at the close of the eighth week in the membrane which forms the side of the skull in the temporal region and gives rise to a squa- mosal bone {s), which later unites with the petrous to form the squamosal portion of the adult temporal, and another membrane bone, the tympanic (t), develops from a center appearing in the mesenchyme surrounding the external auditory meatus, and later also fuses with the petrous to form the floor and sides of the external meatus, giving attachment at its inner edge to the tympanic membrane. Finally, the styloid process is developed from the upper part of the second branchial arch, whose history will be considered later. The various ossifications which form in the chondrocranium and the portions of the adult skull which represent thenj are shown in the following table. i8o THE MEMBRANE BONES OF THE SKULL Region op Chondrocranium OssmcATiON Parts or Adult Skull Basioccipital Basilar process. Occipital Exoccipitals Condyles. Supraoccipital Squamous portion below superior nuchal line. Basisphenoid Presphenoid Body. Sphenoidal LinguliE Alisphenoids Greater wings (in part). Orbitosphenoids Lesser wings. Lamina perpendicularis. Mesethmoid Crista galli. Nasal septum. Lateral masses. Ethmoidal Ectethmoids Inferior concha. Sphenoidal concha. Superior concha. Middle concha. Mastoid. Periotic capsule Petrous. The Membrane Bones of the Skull. — In the membrane form- ing the sides and roof of the skull in the second stage of its develop- ment ossifications appear, which give rise, in addition to the in- terparietal and squamosal bones already mentioned in connection with the occipital and temporal, to the parietals and frontal. Each of the former bones develops from a single center which appears at the end of the eighth week, while the frontal is formed at about the same time from two centers situated symmetrically on each side of the median line and eventually fusing completely to form a single bone, although more or less distinct indications of a median suture, the metopic, are not infrequently present. Furthermore, ossifications appear in the mesenchyme of the facial region to form the nasal, lachrymal, and zygomatic bones, all of which arise from single centers of ossification. In the case of each zygomatic bone, however, three osseous thickenings appear on the inner surface of the original ossification, which then dis- appears and the thickenings unite to form the adult bone, though occasionally one or more of their lines of union may persist, pro- ducing a bipartite or tripartite zygomatic. OSSIFICATION OF BRANCHIAL ARCH SKELETON l8l The vomer, which has already been described, belongs also strictly to the category of membrane bones, as do also the maxillae and the palatines; these latter, however, primarily belonging to the branchial arch skeleton, with which they will be considered. The purely membrane bones in the skull, are, then, the following: Interparietals Part of squamous portion of occipital Pterygoids Medial pterygoid plates. Squamosals Squamous portions of temporals. Tympanies Tympanic plates of temporals. Parietals. Frontal. Nasals. Lachrymals. Zygomatics. Vomer. The Ossification of the Branchial Arch Skeleton.^ — It has been seen (p. 173) that a cartilaginous bar develops only in th6 mandibular process of the first branchial arch. In the maxillary process no cartilaginous skeleton forms, but two membrane bones, the palatine and maxilla, are devel- oped in it, their cartilaginous repre- sentatives, which are to be found in lower vertebrates, having been sup- , , , . , , Fig. 112. — Diagram of the pressed by a condensation of the ossifications of which the development. The palatine bone maxilla is Composed, as seen ^ _ ^ _ FROM THE Outer Surface. The develops from a single center of OSSi- Arrow Passes through the In- j. .. 1 . r 1. •11 1 FRAORBiTAL Canal. — (From von fication, but for each maxtlla no less spee, after Sappey.) than five centers have been described (Fig. 112). One of these gives rise to so much of the alveolar border of the bone as contains the bicuspid and molar teeth; a second forms the nasal process, and the part of the alveolar border which con- tains the canine tooth; a third the portion which contains the incisor teeth; while the fourth and fifth centers lie above the first and ^ve rise to the inner and outer portions of the orbital plate and the body of the bone. The first, second, fourth, and fifth l82- OSSIFICATION OF BRANCHIAL ARCH SKELETON portions early unite together, but the third center, which really lies in the ventral part of the nasal process, remains separate for some time, forming what is termed the premaxilla, a bone which remains permanently distinct in the majority of the lower mammals. The above is the generally accepted view as to the development of the maxilla. Mall, however, maintains that it has but two centers of ossification, one giving rise to the premaxilla and the other to the rest of the bone. The maxillary center makes its appearance about the middle of the sixth week. irAT Pig. 113. — Model of Right Half of Mandible of a Fetus 95 mm. in Length SEEN FROM THE MeSIAL SURFACE. Ci and C2, Accessory cartilages; Ck. T., chorda tympani; Cr., cartilage for coro- noid process; Cy., cartilage for condyloid process; Mai., malleus; M.C., Meckel's cartilage; N.Al., inferior alveolar nerve; N. Aur., auriculo-temporal nerve; N.L,. lingual nerve; N. Mh, mylo-hyoid nerve; N.T., trigeminal nerve; Sy., symphy- sis. — (Low.) Since the condition known as hare-lip results from a failure of the maxillary process to unite completely with the frontonasal process (see p. 102), and since the premaxilla develops in the latter and the maxilla in the former, the cleft may pass between these two bones and prevent their union (see also p. 286). The upper end of Meckel's cartilage passes between the tym- panic bone and the outer surface of the periotic capsule and thus comes to lie apparently within the tympanic cavity of the ear; this portion of the cartilage divides into two parts which ossify to form two of the bones of the middle ear, the malleus and iffcus, a description of whose further development may be postponed OSSIFICATION OF BRANCHIAL ARCH SKELETON 183 until a later chapter. At about the middle of the sixth week of development a plate of membrane bone appears to the outer side of the lower portion of the cartilage and gradually extends to form the body and ramus of the mandible. Fig. 114. — Diagram showing the Categories to which the Bones of the Skull Belong. The unshaded bones are membrane bones, the heavily shaded represent the chondrocranium, while the black represents the branchial arch elements. AS, Ali- phenoid; ExO, exoccipital; F, frontal; Hy, hyoid; IP, interparietal; Z, zygomatic; Mn, mandible; Mx, maxilla; NA, nasal; P, parietal; Pe, periotic; 50, supraoccipital; Sq, squamosal; St, styloid process; Th, thyreoid cartilage; Ty, tympanic. In the region of the |3ody the bone develops so as to enclose the cartilage, together with the inferior alveolar (dental) nerve which lies to the outer side of the cartilage, but in the region of the ramus the bone remains entirely to the outer side of the cartilage 1 84 OSSIFICATION OF BRANCHIAL ARCH SKELETON and nerve, whence the position of the mandibular foramen on the inner surface of the adult bone. The anterior portion of Meckel's cartilage becomes ossified by the extension of ossification from the membrane bone into it, the portion corresponding to the body of the bone behind the mental foramen disappears and the portion above the mandibular foramen is said to become transformed into fibrous connective tissue and to persist as the spheno-mandibular ligament. At the upper extremity of the ramus two nodules of cartilage develop, quite independently, however, of Meckel's cartilage (Fig. 113, Cr and Cy), and ossification extends into these from the ramus to form the coronoid and condyloid processes. And, finally, two other independent cartilages appear toward the anterior extremity of each half of the bone, one at the alveolar (Ci) and the other at the lower border (C2), and these also are later incorporated into the bone without developing special cen- ters of ossification. Each half of the mandible thus ossifies from a single center, and is essentially a membrane bone replacing a cartilaginous precursor. At birth the two halves are united at the symphysis by fibrous tissue, into which ossification extends later, union occurring in the first or second year. The upper part of the cartilage of the second branchial arch also comes into relation with the tympanic cavity and ossifies to form the styloid process of the temporal bone. The succeeding moiety of the cartilage undergoes degeneration to form the stylo- hyoid ligament, while its most ventral portion ossifies as the lesser cornu of the hyoid bone. The great variability which may be observed in the length of the styloid processes and of the lesser cor- nua of the hyoid depends upon the extent to which the ossification of the original cartilage proceeds, the length of the stylo-hyoid ligaments being in inverse ratio to the length of the processes or cornua. The greater cornua of the hyoid are formed by the ossifi- cation of the cartilages of the third arch, and the body of the bone is formed from a cartilaginous plate, the copula, which unites the ventral ends of the two arches concerned. Finally, the cartilages of the fourth and fifth branchial arches ist arch. 2d arch. DEVELOPMENT OF THE APPENDICULAR SKELETON 185 early fuse together to form a plate of cartilage, and the two plates of opposite sides unite by their ventral edges to form the thyreoid cartilage of the larynx. The accompanying diagram (Fig. 114) shows the various structures derived from the branchial arch skeleton, as well as some of the other elements of the skull, and a resume of the fate of the branchial arches may be stated in tabular form as follows, the parts represented by cartilage which becomes replaced by mem- brane bone being printed in italics, while membrane bones which have no cartilaginous representatives are enclosed in brackets : (Maxilla). (Palatine). Malleus. Incus. Spheno-mandibular ligament. Mandible. Styloid process of the temporal. Stylo-hyoid ligament. Lesser cornu of hyoid. 3d arch , Greater cornu of hyoid. 4th and 5th arches Thyreoid cartilage o* larynx. The Development of the Appendicular Skeleton. — While the greater portion of the axial skeleton is formed from the sclerotomes of the mesodermic somites, the appendicular skeleton is derived from the somatic mesenchyme, which is not divided into meta- meres. This mesenchyme forms the core of the limb bud and becomes converted into cartilage, by the ossification of which all the bones of the limbs, with the possible exception of the clavicle, are formed. The clavicle is the first bone of the skeleton to ossify, two centers appearing for each bone at about the sixth week of development. Before ossification the bone is represented by a bar of tissue of peculiar character, it being difficult to say whether it is to be regarded as cartilage that has not become thoroughly differentiated histologically, or as some special variety of connective tissue. In this the two centers of ossification appear, one corresponding to 1 86 DEVELOPMENT OF THE APPENDICULAR SKELETON the sternal and the other to the acromial end of the bone, and these are at first united by a bridge of the original tissue. This ossi- fies later, so that the two centers are united, and at either end of the bone true cartilage appears, into which the ossification extends. This mode of development from two centers explains a defect occa- sionally observed in this bone, one or other of its portions, usually the acromial one, being wanting. This is the result of a failure of the acromial center. Pig. 115. — The Ossification Centers of the Scapula. a, b, and c. Secondary centers for the angle, vertebral border, and acro- mion; CO, center for the coracoid proc- ess. — (Testut.) Fig. 116. — Reconstruction of an Embryonic Carpus. c, Centrale; cu, triquetral; lu, lunate m, capitate; p, pisiform; sc, navicular; t, greater multangular; tr, lesser multan- gular; u, hamate. The scapula is at first a single plate of cartilage in which two centers of ossification appear. One of these gives rise to the body and the spine, while the other produces the coracoid process (Fig. 115, co), the rudimentary representative of the coracoid bone which extends between the scapula and sternum in the lower vertebrates. The coracoid does not unite with the body until about the fifteenth year, and secondary centers which give rise to the vertebral edge (b) and inferior angle of the bone (a) and to the acromion process (c) unite with the rest of the bone at about the twentieth year. DEVELOPMENT OF THE APPENDICULAR SKELETON 187 The humerus and the bones of the forearm are t)^ical long bones, each of which develops from a primary center, which gives rise to the shaft, and has, in addition, two or more epiphysial centers. In the humerus an epiphysial center appears for the head, another for the greater tuberosity, and usually a third for the lesser tuberosity, while at the distal end there is a center for each epicondyle, one for the trochlea and one for the capitulum, the fusion of these various epiphyses with the shaft taking place between the seventeenth and twentieth years. The radius and ulna each possesses a single epiphysial center for each extremity in addition to the primary center for the shaft, the proximal epi- physial center for the ulna giving rise to the tip of the olecranon process. The embryological development of the carpus is somewhat complicated. A cartilage is found representing each of the bones normally ocurring in the adult (Fig. ii6), and these are arranged in two distinct rows : a proximal one consisting of three elements, named from their relation to the bones of the forearm, radiale, intermedium, and ulnare; and a distal one composed of four elements, termed carpalia. In addition, a cartilage, termed the pisiform, is found on the ulnar side of the proximal row and is generally regarded as a sesamoid cartilage developed in the tendon of the flexor carpi ulnaris, and furthermore a number of inconstant cartilages have been observed whose significance in the majority of cases is more or less obscure. These accessory cartilages either disappear in later stages of development or fuse with neighboring cartilages, or, in rare cases, ossify and form distinct elements of the carpus. One of them, however, occurs so frequently as almost to deserve classification as a constant element; it is known as the cent rale (Fig. 1 16, c) and occupies a position between the carti- lages of the proximal and distal rows and apparently corresponds t6 a cartilage typically present in lower forms and ossifying to form a distinct bone. In the human carpus its fate varies, as it may either disappear or unite with other cartilages,Uhat with which it most usually fuses being probably the radiale. There is evidence also to show that another of the accessory cartilages unites i88 DEVELOPMENT OF THE APPENDICULAR SKELETON with the ulnar element of the distal row, representing the carpale V typically present in lower forms. Each of the elements corresponding to an adult bone ossifies from a single center with the exception of carpale iv-v which has two centers, a further indication of its composite character. The relation of the cartilages to the adult bones may be seen from the table given on p. 190. With regard to the metacarpals and phalanges, it need merely be stated that each develops from a single primary center for the shaft and one secondary epiphysial center. The primary center ap- pears at about the middle of the shaft except in the terminal phalanges, in which it appears at the distal end of the cartilage. The epiphyses for the metacar- pals are at the distal ends of the bones, except in the case of the metacarpal of the thumb, which resembles the phalanges in having its epiphysis at the proximal end. Each innominate bone appears as a somewhat oval plate of cartilage whose long axis is di- rected almost at right angles to the vertebral column and which is in close relation with the fourth and fifth sacral vertebrae. As development proceeds a rotation of the cartilage, accom- panied by a slight shifting of position, occurs, so that eventually the plate has its long axis almost parallel with the vertebral column and is in relation with the first three sacrals. Ossi- fication appears at three points in each cartilage, one in the upper part to form the j/iMW (Fig. iiy, il), and two in the lower part, the anterior of these giving rise to the pubis (p), while the pos- terior produces the ischium (is). At birth these three bones are Fig. 117. — The Ossification Cen- ters OF THE OS InNOMINATUM. a, b, c, and d. Secondary centers for the crest, anterior inferior spine, symphysis, and ischial tuberosity; il, ilium; is, ischium; p, pubis. — {Testut.) DEVELOPl^NT OF THE APPENDICULAR SKELETON 189 still separated from one another by a Y-shaped piece of cartilage whose three limbs meet at the bottom of the acetabulum, but later a secondary center appears in this cartilage and unites the three bones together. The central part of the lower half of each original cartilage plate does not undergo complete chondrifica- tion, but remains membranous, constituting the obturator mem- brane which closes the obturator foramen. In addition to the Y-shaped secondary center, other epiphysial centers appear in the prominent portions of the cartilage, such as the pubic crest (Fig. 117, c,) the ischial tuberosity (d), the anterior inferior spine (b) and the crest of the ilium (a), and unite with the rest of the bone at about the twentieth year. The femur, tibia, &nd fibula each develop from a single primary center for the shaft and an upper and a lower epiphysial center, the femur possessing, in addition, epiphysial centers for the greater and lesser trochanters (Fig. 94). The patella does not belong to the same category as the other bones, but resembles the pisiform bone of the carpus in being a sesamoid bone, developed in the tendon of the quadriceps extensor cruris. Its cartilage does not appear until the fourth month of intrauterine life, when most of the primary centers for other bones have already appeared, and its ossification does not begin until the third year after birth. The tarsus, like the carpus, consists of a proximal row of three cartilages, termed the tibiale, the intermedium, and thefibulare, and of a distal row of four tarsalia. Between these two rows a single cartilage, the centrale, is interposed. Each of these cartilages ossifies from a single center, that of the intermedium early fusing with the tibiale, though it occasionally remains distinct as the os trigonum, and from a comparison with lower forms it seems probable that the fibular cartilage of the distal row really repre- sents two separate elements, there being, properly speaking, five tarsalia instead of four. The fibulare, in addition to its primary center, possesses also an epiphysial center, which develops at the point of insertion of the tendo Achillis. A comparison of the carpal and tarsal cartilages and their relations to the adult bones may be seen from the following table ; IQO DEVELOPMENT OF THE JOINTS Carpus Tarsus Cartilages Bones Bones Cartilages Radiale Intermedium Ulnare Sesamoid cartilage Centrale Carpale I Carpale II Carpale III Carpale IV Carpale V , Navicular Lunate Triquetral Pisiform Fuses with navi- cular Gr. multangular Less, multangular Capitate Hamate Talus Calcaneus j Tibiale [ Intermedium Fibulare Navicular I St Cuneiform 2d Cuneiform 3d Cuneiform Cuboid Centrale Tarsale I Tarsale II Tarsale III 1 Tarsale IV 1 Tarsale V The development of the metatarsals and phalanges is exactly similar to that of the corresponding bones of the hand (see p. 182) . The Development of the Joints.— The mesenchyme which primarily represents each vertebra, or the skull, or the skeleton of a limb, is at first a continuous mass, and when it becomes con- verted into cartilage this also may be continuous, as in the skull, or may appear as a number of distinct parts united by unmodified portions of the mesenchyme. In the former case the various ossifi- cations as they extend will come into contact with their neigh- bors and will either fuse with them or will articulate with them directly, forming a suture. When, however, a portion of unmodified mesenchyme inter- venes between two cartilages, the mode of articulation of the bones formed from these cartilages will vary. The intermediate mesenchyme may in time undergo chondrification and unite the bones in an almost immovable articulation known as a syn- chondrosis {e.g., the articulation of the first rib with the sternum); or a cavity may appear in the center of the intervening cartilage so that a slight amount of movement of the two bones is possible, forming an amphiarthrosis {e.g., the symphysis pubis); or, finally, the intermediate mesenchyme may not chondrify, but its per- ipheral portions may become converted into a dense sheath of connective tissue (Fig. 118, c) which surrounds the adjacent ends DEVELOPMENT OF THE JOINTS 191 of the two bones like a sleeve, forming the articular capsule, while the central portions degenerate to form a cavity. The bones which enter into such an articulation are more or less freely mov- able upon one another and the joint is termed a diarthrosis (e.g., the knee- or shoulder- joint). In a diarthrosis the connective-tissue cells near the inner surface of the capsule arrange themselves in a layer to form a synovial membrane for the joint, and portions of the capsule may thicken to form special bands, the reinforcing ligaments, while other strong fibrous bands, which may pass from one bone to the other, forming accessory Ugaments, are shown by comparative Fig. 118. — Longitudinal Section through the Joint of the Great Toe in an Embryo of 4.5 cm. c. Articular capsule; i, intermediate mesenchyme which has almost disappeared in the center; p^ and p', cartilages of the first and second phalanges. — (Nicholas.) studies to be in many cases degenerated portions of what were originally muscles. In certain diarthroses, such as the temporo-mandibular and sterno-clavicular, the whole of the central portions of the inter- mediate mesenchyme does not degenerate, but it is converted into a fibro-cartilage, between each surface of which and the adjacent bone there is a cavity. These interarticular cartilages seem, in the sterno-clavicular joints, to represent the sternal ends of a bone existing in lower vertebrates and known as the precoracoid, but it seems doubtful if those of the temporo-mandibular and knee- joir"^' ^ — --I--- -•-—•-^ ^1 — jjQgj recent observations on 192 LITERATURE their development tending to derive them from the intermediate mesenchyme. From their mode of development it is evident that the cavities of diarthrodial joints are completely closed and their walls, except where they are formed by cartilage, are lined by a continuous layer of synovial cells. Ligaments or tendons, which, at first sight, appear to traverse the cavities of certain joints, are in reality excluded from them, being lined by a sheath of synovial cells continuous with the layer lining the general cavity. Thus, the tendon of the long head of the biceps, which seems to traverse the shoulder-joint is, in the fetus, entirely outside the articular capsule, upon which it rests. Later it sinks in toward the joint cavity, pushing the articular capsule before it, so that it lies at first in a groove in the capsule, which later on becomes converted into a canal and, finally, separates from the rest of the capsule except at its extremities, forming a cylindrical canal, open at either end, traversing the joint cavity and containing the tendon of the biceps. The ligamentum teres of the hip-joint is similarly excluded from the joint cavity by a sheath of synovium,' which extends outward around it from the bottom of the acetabular fossa to the depression in the head of the femur, and in the knee-joint the crucial ligaments are also ex- cluded from the cavity by a reflection of the synovium. This joint, indeed, is in the fetus incompletely divided into two parts, one corre- sponding to each femoral condyle, by a partition which extends back- ward from the patellar ligament to the crucial ligaments, remains of this partition persisting in the adult as the so-called ligamentum mucosum. LITERATURE L. B. Arey: The Origin, Growth, and Fate of Osteoclasts and Their Relation to Bone Resorption," Amer. Journ. Anal., xxvi, 1920. C. R. Bardeen: "The Development of the Thoracic Vertebrae in Man," Amer. Journ. Anat., rv, 1905. C. R. Bardeen: "Studies of the Development of the Human Skeleton,'' Amer. Journ. Anat., w, 1905. C. R. Bardeen: "Early Development of the Cervical Vertebrae and the Base of Occipital Bone in Man," Amer. Journ. Anat., \{n, igo8. C. R. Bardeen: "Vertebral Regional Determination in Young Human Embryos," Anal. Record, 11, 1908. E. T. Bell: "On the Histogenesis of the Adipose Tissue of the Ox," Amer. Journ. Anal., IX, 1909. A. Bernays: "Die Entwicklungsgeschichte des Kniegelenks des Menschen mit Bemerkungen uber die Gelenke im Allgemeinen," Morpholog. Jahrbuch, iv, 1678. E. Dursy: "Zur Entwicklungsgeschichte des Kopfes des Menschen und der hSheren Wirbelthiere," Tubingen, 1869. E. Fawcett: "On the Development, Ossification and Growth of the Palate Bone," Journ. Anat. and Phys., xl, 1906. LITERATURE 1 93 E. Fawcett: "Notes on the Development of the Human Sphenoid," Journ. Anat. and Phys., XLiv, 1910. E. Fawcett: "The Development of the Human Maxilla, Vomer and Paraseptal Cartilages,'' Journ. Anat. andPhys.,XLV, 1911. E. Fawcett: "The Development and Ossification of the Human Clavicle," Journ. Anat. and Phys., XLvn, 1913. A. Fkoriep: "Zur Entwicklungsgeschichte der Wirbelsaule, insbesondere des Atlas und Epistropheus und der Occipitalregion," Archivfiir Anat. und Physiol., Anal. Abth., 1886. E. Gaotp: "Alte Probleme und neuere Arbeiten^ tiber den WirbeltierschSdel," Ergeb. der Anat. und Entwichlungsgesch., x, 1901. C. Geoenbaur: "Ein Fall von erblichem Mangel der Pars acromialis Claviculae, mit Bemerkungen iiber die Entwicklung der Clavicula," Jenaische Zeilschr. fiir medic. Wissensch., i, 1864. J. GoLowiNSKi: "Zur Kenntnis der Histogenese der Bindegewebsfibrillen," Anat. Hefte, xxxin, 1907. E. Gkafenberg: "Die Entwicklimg der Knochen, Muskeln und Nerven der Hand und der fur die Bewegungen der Hand bestimmten Muskeln des Unterarms," Anat. Hefte, xxx, 1906. F. B. Hanson: "The Development of the Sternum in Sus Scrofa, Anat. Record, xvn, 1919. Henke and Reyher: "Studien uber die Entwickelung der Extremitaten des Menschen, insbesondere der Gelenkflachen," Siizungsberichte der kais. Akad. Wien, ixx, 1875. M, Jakoby: "Beitrage zur Kenntnis des menschlichen Primordialcraniums," Archiv fur mikrosk. Anat., xliv, 1894. K. Kjellberg: "Beitrage zur Entwicklungsgeschichte des Kiefergelenks," Morph. Jahrbuch, xxxil, 1904. H. Leboucq: "Recherches sur la morphologie du carpe chez les mammiferes,'' Archives de Biolog., v, 1884. G. Levi: "Beitrag zum Studium der Entwickelung des knorpeligen Primordialcran- iums des Menschen," Archiv fur mikrosk. Anat., lv, 1900. A. Linck: "Beitrage zur Kenntnis der menschlichen Chorda doralis in Hals-und Kopfskelett, etc.," Anat. Hefte, xlii, 1911. A. Low: "Further Observations on the Ossification of the Human Lower Jaw," Journ. Anat. and Phys., XLiv, 1910. C. C. Macklin: "The Skull of a Human Fetus of 40 mm.," Amer. Journ. Anat., xvi, 1914. M. Lucben: " D6veloppement de I'articulation du genou et formation du ligament adipeux," Bibliogr. Anat., xin, 1904. F. P. Mall: "The Development of the Connective Tissues from the Connective- tissue Syncytium," Amer. Jour. Anat., i, 1902. F. P. Mall: "On Ossification Centers in Human Embryos Less Than One Hundred Days Old," Amer. Journ. Anat., v, 1906. F. Merkel: " Betrachtungen iiber die Entwicklung des Bindegewebes," Anat. Hefte, XXXVIII, 1909. 194 LITERATURE W. VAK Noorden: "Beitrag zur Anatomic der knorpeligen Schadelbasis menschlicher Embryonen,'' Archhfiir Anat. und Physiol., Anat. Abth., 1887. A. M. Paterson: "The Human Sternum," Liverpool, 1904. K. Peter: "Anlage und Homologie der Muscheln des Menschen und der Saugetiere, Arch. Jiir mikrosk. Anat., LX, 1902. J. W. Pryor : " The Chronology and Order of Ossification of the Bones of the Human Carpus," Bulletin State Univ., Lexington, Ky., 1908. Rambaut EI Renauxt: " Origine et dSveloppement des Os," Paris, 1864. E. Rosenberg: "Ueber die Entwickelung der Wirbelsaule und das Centrale carpi des Menschen," -Morpholog. Jahrbuch, I, 1876. H. AND H. RotrviiRE: "Sur le d6veloppement de I'antre mastoidien et les cellules mastoidiennes," Bibliogr. Anat., xx, 1910. G. Ruge: "Unter^uchungen fiber die Entwickelungsvorgange am Brustbein des Menschen," Morpholog. Jahrbuch, vi, 1880. J. P. Schaffer: "The Lateral Wall of the Cavum Nasi' in Man, with Especial Reference to the Various Developmental Stages," Journ. Morph., xxi, 1910. J. P. Schaffer: "The Sinus Maxillaris and its Relations in the Embryo, Child and Adult Man," Amer. Journ. Anat., x, 1910. G. Thii-enhjs : " Untersuchungen iiber die morphologische Bedeutung accessorischer Elemente am menschlichen Carpus (und Tarsus)," Morpholog. Arbmten,v, 1896. K. ToLDT, Jr.: "Entwicklung und Struktur des menschlichen Jochbeines," Sitz- ungsber. k. Acad. Wissensch. Wien, Math.-naturwiss Kl., cxi, 1902. A. Vinogradoff: " Dfiveloppement de I'articulation temporo-maxillaire chez I'homme dans la perlode intrauterine," Internal. Monatsschr. Anal. Phys., xxvn, 1910. R. H. Whitehead and J. A. Waddell: "The Early Development of the Mammalian Sternum," Amer. Journ. Anat., xn, 1911. L. W. Williams: "The Later Development of the Notochord," Amer. Journ. Anat., vni, igo8. E. Zuckerkandl: "Ueber den Jacobsonschen Knorpel und die Ossifikation des Pflugscharbeines," Sitzb. Akad. Wiss. Wien., cxvii, 1908. CHAPTER VIII THE DEVELOPMENT OF THE MUSCULAR SYSTEM Two forms of muscular tissue exist in the human body, the striated tissue, which forms the skeletal muscles and is under the control of the central nervous system, and the non-striated, which is controlled by the sympathetic nervous system and is found in the skin, in the walls of the digestive tract, the blood-vessels and lymphatics, and in connection with the genito-urinary apparatus. In the walls of the heart a muscle tissue occurs which is frequently regarded as a third form, characterized by being under control of the sympathetic system and yet being striated; it is, however, in its origin much more nearly alhed to the non-striated than to the striated form of tissue, and will be considered a variety of the former. The Histogenesis of Non-Striated Muscular Tissue. — With the exception of the sphincter and dilator of the pupil and the muscles of the sudoriparous glands, which are apparently formed from the ectoderm, all the non-striated muscle tissue of the body is formed by the conversion of mesenchyme cells into muscle-fibers. The details of this process have been worked out by McGill for the musculature of the digestive and respiratory tracts of the pig and are as follows: The mesenchyme surrounding the mucosa in these tracts is at first a loose syncytium (Fig. 119, m) and in the regions where the muscle tissue is to form, a condensation of the mesenchyme occurs followed by an elongation of the mesenchyme cells and their nuclei, so that the muscle layers become clearly distinguishable from the neighboring undifferentiated tissue (Fig. 119, mm). Fibrils of two kinds then begin to appear in the cyto- plasm of the muscle cells. Coarse fibrils (f.c) make their appear- ance as rows of granules, which enlarge and increase in number until they finally fuse to form homogeneous fibrils that are at 196 HISTOGENESIS OF NON-STRIATED MUSCULAR TISSUE -■'\ Jf Pig. 119. — Longitudinal Section of the Lower Part of the Oesophagus OF A Pig Embryo of 15 mm, Showing the Histogenesis of the Non-striated Musculature. 6, Basement membrane; e, epithelium; f.c, coarse fibril; /,/., fine fibril; ga, gang- lion of Auerbach's plexus; gm, ganglion of Meissner's plexus; m, mesenchyme; mm, muscularis mucosae; ph, protoplasmic bridge; vf, varicose fibril. — (McGill.) HISTOGENESIS OF NON-STRIATED MUSCULAR TISSUE 197 first varicose, but later become of uniform caliber. Fine fibrils (/./) which are homogeneous from the first, make their appearance after the coarse ones and in some cases seem to be formed by the splitting of the latter. They are scattered uniformly throughout the cytoplasm of the muscle cells and increase in number as development proceeds, while the coarse fibrils diminish and may be entirely wanting in the adult tissue. Some of the mesenchyme cells in each muscle sheet fail to undergo the differentiation just described and multiply to form the interstitial connective tissue, which usually divides the muscle cells into more or less distinct bundles. Traces of the original syncytial nature of the tissue are to be seen in the intercellular bridges that occur between the non-striated muscle cells of many adult forms. The cells from which the heart musculature develops are at first of the usual well defined embryonic type, but, as develop- ment proceeds, they become ir- regularly stellate in form, the processes of neighboring cells fuse and, eventually, there is formed a continuous mass of protoplasm or syncytium in which all traces of cell boundaries are lacking (Fig. 120). While the individual cells, or myoblasts as they are termed, are still recognizable, granules appear in their cytoplasm, and these arrange themselves in rows and unite to form slender fibrils, which at first do not extend be- yond the limits of the myoblasts in which they have appeared, but later, as the fusion of the cells proceeds, are continued from one cell territory into the other through considerable stretches of the syncytium, without regard to the original cell areas. Fig. 120. — Section through the Heart-wall of a Duck Embryo of Three Days. — (M. Heidenkain.) 1 98 "HISTOGENESIS OF STRIATED MUSCLE TISSUE The fibrils multiply, apparently by longitudinal division, and arrange themselves in circles around areas of the syncytium (com- pare Fig. i2i). As the multiplication of the fibrils continues those newly formed arrange themselves around the interior of each of the original circles and gradually occupy the entire cytoplasm, or sarcoplasm as it may now be termed, except immediately around the nuclei where, even in the adult, a certain amount of un- differentiated sarcoplasm persists. The fibrils when first formed are apparently homogeneous, but later they become differentiated into two distinct substances which alternate with one another Pig. 121. — Cross-section OF A Muscle FROM THE Thigh OF A Pig Embryo 75 mm. Long. A, Central nucleus; B, new peripheral nucleus. — (Macallum.) throughout the length of the fibril and produce the characteristic transverse striation of the tissue. Finally stronger interrupted transverse bands of so-called cement substance appear, dividing the tissue into areas which have usually been regarded as rep- resenting the original myoblasts, but are really devoid of signifi- cance as cells, the tissue remaining, strictly speaking, a syncytium. The Histogenesis of Striated Muscle Tissue. — The histo- genesis of striated or voluntary muscle tissue resembles very closely that which has just been described for the heart muscle. There is a similar formation of a syncytium by the fusion of the DEVELOPMENT OF SKELETAL MUSCLES 199 cells of the myotomes, an appearance of granules which unite to form fibrils, an increase of the fibrils by longitudinal division and a primary arrangement of the fibrils around the periphery of areas of sarcoplasm (Fig. 121), each of which represents a muscle fiber. In addition there is an active proliferation of the nuclei of the original myoblasts, the new nuclei arranging themselves more or less regularly in rows and later migrating from their original central position to the periphery of the fibers, and, in the limb .muscles, the development is further complicated by a process of degeneration which affects groups of muscle fibers, so that bundles of normal fibers are separated by strands of degenerated tissue in which the fibrils have disappeared, the nuclei have become pale and the sarcoplasm vacuolated and homogeneous. Later the degenerated tissue seems to disappear entirely and mesenchyma- tous connective tissue grows in between the persistingfibers, group- ing them into bundles and the bundles into the individual muscles. So long as the formation of new fibrils continues, the increase in the thickness of a muscle is probably due to a certain extent to an increase in the actual number of fibers, which results from the division of those already existing. Subsequently, however, this mode of growth ceases, the further increase of the muscle depending upon an increase in size of its constituent elements (Macallum). The Development of the Skeletal Muscles. — It has already been pointed out that all the skeletal muscles of the trunk are derived from the myotomes of the mesodermic somites. Those that are primarily associated with the branchial arches, however, have their origin from the unsegmented ventral mesoderm and this seems also to be the origin of the muscles developed in the limb buds, these being differentiated from the somatic mesen- chyme which forms the axial cores of the Umb buds. The various fibers of each myotome are at first loosely arranged but later they become more compact and are arranged parallel with one another, their long axes being directed antero-posteriorly. This stage is also transitory, however, the fibers of each myotome undergoing various modifications to produce the conditions 200 DEVELOPMENT OF SKELETAL MUSCLES existing in the adult, in which the original segmental arrangement of the fibers can be perceived in comparatively few muscles. The exact nature of these modifications is almost unknown from direct observation, but since the relation between a nerve and the muscle fibers supplied by it is established at a very early period of development and persists throughout life no matter what changes of fusion, splitting, or migration the muscle may undergo, it is possible to trace out more or less completely the history of the various muscles by determining their segmental innervation. It is known, for example, that the latissimus dorsi arises in the region of the seventh and eighth* cervical myotomes, but later undergoes a migration, becoming attached to the lower thoracic and lumbar vertebra and to the crest of the ilium, far away from its place of origin (Mall), and yet it retains its nerve- supply from the seventh and eighth cervical nerves with which it was originally associated, its nerve-supply consequently indicat- ing the extent of its migration. By following the indications thus afforded, it may be seen that the changes that tend to obscure the primary segmental arrangement of the muscle fibers may be referred to one or more of the following processes : 1. A longitudinal sphtting into two or more portions, a process well illustrated by the trapezius and sternomastoid, which have differentiated by the longitudinal splitting of a single sheet and contain therefore portions of the same muscle-segments. The sternohyoid and omohyoid have also differentiated by the same process, and, indeed, it is of frequent occurrence. 2. A tangential splitting into two or more layers. Examples of this are also abundant and are afforded by the muscles of the fourth, fifth, and sixth layers of the back, as recognized in English text-books of anatomy, by the two oblique' and the transverse layers of the abdominal walls, and by the intercostal muscles and the transversus of the thorax. * This enumeration is based on convenience in associating the myotomes with the nerves which supply them. The myotomes mentioned are those which correspond to the sixth and seventh cervical vertebrae. DEVELOPMENT OF SKELETAL MUSCLES 20I 3- A fusion of portions of successive myotomes to form a single muscle, again a process of frequent occurrence, and well illus- trated by the rectus abdominis (which is formed by the fusion of the ventral portions of the last six or seven thoracic myotomes), or by the superficial portions of the sacro-spinalis. 4. A migration of parts of one or more muscle-segments over others. An example of this process is to be found in the latissimus dorsi, whose history has already been referred to, and it is also beautifully shown by the serratus anterior and the trapezius, both of which have extended far beyond the limits of the segments from which they are derived. 5. A degeneration of portions or the whole of a muscle-segment. This process has played a very considerable part in the evolution "of the muscular system in the vertebrates. When a muscle normally degenerates, it becomes converted into connective tissue, and many of the strong aponeurotic sheets which occur in the body owe their origin to this process. Thus, for example, the aponeurosis connecting the occipital and frontal portions of the occipito-frontalis is formed in this way and is muscular in such forms as the lower monkeys, and a good example is also to be found in the aponeurosis which occupies the interval between the superior and inferior serrati postici, these two muscles being continuous in lower forms. The strong lumbar aponeurosis and the aponeuroses of the obHque and transverse muscles of the abdomen are also good examples. Indeed, in comparing a mammal with a member of one of the lower classes of vertebrates, the greater amount of connective tissue compared with the amount of muscular tissue in the former is very striking, the inference being that these connective-tissue structures (fasciae, aponeuroses, ligaments) represent portions of the muscular tissue of the lower form (Bardeleben). Many of the accessory ligaments occurring in connection with diarthro- dial joints apparently owe their origin to a degeneration of muscle tissue, the fibular lateral ligament of the knee-joint, for instance, being probably a degenerated portion of the peroneus longus, while the sacro-tuberous ligament appears to 202 THE TRUNK MUSCULATUR!^ stand in a similar relation to the long head of the biceps femoris (Sutton). 6. Finally, there may be associated with any of the first four processes a change in the direction of the muscle-fibers. The original antero-posterior direction of the fibers is retained in com- paratively few of the adult muscles and excellent examples of the process here referred to are to be found in the intercostal muscles and the muscles of the abdominal walls. It would occupy too much space in a work of this kind to con- sider in detail the history of each one of the skeletal muscles of the human body, but a statement of the general plan of their development will not be out of place. For convenience the entire system may be divided into three portions — the cranial, trunk and limb musculature; and of these, the trunk musculature' may first be considered. The Trunk Musculature. — It has already been seen (p. 85) that the myotomes at first occupy a dorsal position, becoming prolonged ventrally as development proceeds so as to overlap the somatic mesoderm, until those of opposite sides come into contact in the mid-ventral line. Before this is accompHshed, however, a longitudinal splitting of each myotome occurs, whereby there is separated off a dorsal portion which gives rise to a segment of the dorsal musculature of the trunk and is suppUed by the ramus dorsalis of its corresponding spinal nerve. In the lower vertebrates this separation of each of the trunk myotomes into a dorsal and ventral portion is much more distinct in the adult than it is in man, the two portions being separated by a horizontal plate of connective tissue extending the entire length of the trunk and being attached by its inner edge to the transverse processes of the vertebrae, while peripherally it becomes continuous with the connective tissue of the dermis along a line known as the lateral line. In man the dorsal portion is also much smaller in proportion to the ventral portion than in the lower vertebrates. From this dorsal portion of the myotomes are derived the muscles belonging to the three deepest layers of the dorsal musculature, the more superficial layers being composed of muscles belonging to the THE TRUNK MUSCULATURE 203 limb system. Further longitudinal and tangential divisions and a fusion of successive myotomes bring about the conditions which obtain in the adult dorsal musculature. While the myotomes are still some distance from the mid- ventral hne another longitudinal division affects their ventral edges (Fig. 122), portions being thus separated which later fuse more or less perfectly to form longitudinal bands of muscle, those Pig. 122. — Embryo of 13 mm. showing the Formation of the Rectus Muscle. — (.Mall.) of opposite sides being brought into apposition along the mid- ventral line by the continued growth ventrally of the myotomes. In this way are formed the rectus and pyramidalis muscles of the abdomen and the depressors of the hyoid bone, the genio-hyoid and genio-glossus* in the neck region. In the thoracic region this * This muscle is supplied by the hypoglossal nerve, but for the present purpose it is convenient to regard this as a spinal nerve, as indeed it primarily is. 204 THE TRUNK MUSCULATURE rectus set of muscles, as it may be termed, is not represented except as an anomaly, its absence being probably correlated with the development of the sternum in this region. The lateral portions of the myotomes which intervene between the dorsal and rectus muscles divide tangentially, producing from their dorsal portions in the cervical and lumbar regions muscles, such as the longus capitis and colli and the psoas, which lie be- neath the vertebral column and hence have been termed hypo- skeletal muscles (Huxley). More ventrally three sheets of mus- cles, lying one above the other, are formed, the fibers of each sheet being arranged in a definite direction differing from that found in the other sheets. In the abdomen there are thus formed the two oblique and the transverse muscles together with the quadratus lumborum, in the thorax the intercostals and the transversus thoracis, while in the neck these portions of some of the myo- tomes disappear, those of the remainder giving rise to the scaleni muscles, portions of the trapezius and sternomastoid (Bolk), and possibly the hyoglossus and styloglossus. In the abdominal region, and to a considerable extent in the neck also, the various portions of myotomes fuse together, but in the thorax they retain in the intercostals their original distinctness, being separated by the ribs. The table on p. 205 will show the relation of the various trunk muscles to the portions of the myotomes. The intimate association between the pelvic girdle and the axial skeleton brings about extensive modifications of the posterior trunk myotomes. So far as their dorsal portions are concerned probably all these myotomes as far back as the fifth sacral are represented in the sacro-spinalis, but the ventral portions from the first lumbar myotome onward are greatly modified. The last myotome taking part in the formation of the rectus abdominis is the twelfth thoracic and the last to be represented in the lateral musculature of the abdomen is the first lumbar, the ventral por- tions of the remaining lumbar and of the first and second sacral myotomes having disappeared. The ventral portions of the third and fourth sacral myotomes THE TRUNK MUSCULATURE 205 P< f -a o .a 2 S m bo bo ^ iJ iJ B< Cli CI. X) a 'o •^ 4-) S s "J 2 o -o 1^ 12 a-" « ?) fe s t« t-l M (^ 8-^ S 2 en O M H O « 2o6 THE CRANIAL MUSCULATURE are represented, however, by the levator ani and coccygeus, and are the last myotomes which persist as muscles in the human body, although traces of still more posterior myotomes are to be found in muscles such as the curvator coccygis sometimes developed in connection with the coccygeal vertebrae. The perineal muscles and the, external sphincter ani are also developments of the third and fourth (and second) sacral myo- tomes. At a time when the cloaca (see p. 282) is still present, a sheet of muscles lying close beneath the integument forms a Fig. 123. — Perineal Region of Embryos of (A) Two Months and (B) Four to Five Months, showing the Development of the Perineal Muscles. dc, Nervus dorsalis clitoridis; p, pudendal nerve; sa, sphincter ani; sc, sphincter cloacas; sv, sphincter vaginae. — (Popowsky.) sphincter around its opening (Fig. 123). On the development of the partition which divides the cloaca into rectal and urinogenital portions, the sphincter is also divided, its more posterior por- tion persisting as the external sphincter ani, while the anterior part gradually differentiates into the various perineal muscles (Popowsky). .The Cranial Musculature.— As was pointed out in an earlier chapter, the existence of distinct mesodermic somites has not yet been completely demonstrated in the head of the human embryo, but in lower forms, such as the elasmobranch fishes, they are clearly distinguishable, and it may be supposed that their indis- tinctness in man is a secondary condition. Exactly how many of these somites are represented in the mammalian head it is im- possible to say, but it seems probable, from comparison with lower THE CRANIAL MUSCULATURE 207 forms, that there is a considerable number. The majority of them, however, early undergo degeneration, and in the adult condition only three are recognizable, two of which are prasoral in position and one postoral. The myotomes of the anterior praeoral segment give rise to the muscles of the eye supplied by the third cranial nerve, those of the posterior one furnish the superior obhque muscles innervated by the fourth nerve, while from the postoral myotomes the lateral recti, supplied by the sixth nerve, are developed. The muscles supplied by the hypoglossal nerve are also derived from myotomes, but they have already been considered in connection with the trunk musculature. The remaining muscles of the head differ from the voluntary muscles of the trunk in the fact that they are derived from the branchiomeres formed by the segmentation of the cephalic ventral mesoderm. These muscles, therefore, are not to be regarded as equivalent to the myotomic muscles if their embryological origin is to be taken as a criterion of equivalency, and it would seem, from the fact that they are innervated by nerves fundamentally distinct from those which supply the myotomic muscles, that this criterion is a good one. They must be regarded, therefore, as belonging to a special category, and may be termed hranchiomeric muscles to distinguish thetn from the myotomic set. If their embryological origin be taken as a basis for homology, it is clear that they should be regarded as equivalent to the muscles derived from the ventral mesoderm of the trunk, and these, as has been seen, are the non-striated muscles associated with the viscera, among which may be included the striated heart muscle. At first sight this homology seems decidedly strained, chiefly because long-continued custom has regarded the histological and physiological peculiarities of striated and non-striated muscle tissue as fundamental. It may be pointed out, however, that the hranchiomeric muscles are, strictly speaking, visceral muscles, and indeed give rise to muscle sheets (the constrictors of the pharynx) which surround the upper or pharyngeal portion of the di- gestive tract. It is possible, then, that the homology is not so strained as might appear, but further discussion of it may profitably be de- ferred until the cranial nerves are under consideration. The skeleton of the first branchial arch becomes converted partly into the jaw apparatus and partly into auditory ossicles, 208 THE CRANIAL MUSCULATURE Fig. 124. — Head of Embryos {A) of Two Months and (B) of ThreeIMonths SHOWING THE EXTENSION OF THE SEVENTH NeRVE UPON THE FaCE. (PopOWsky.) THE CRANIAL MUSCULATURE 209 and the muscles derived from the corresponding branchiomere become the muscles of mastication (the temporal, masseter, and pterygoids), the mylohyoid, anterior belly of the digastric, the tensor veli palatini and the tensor tympani. The nerve which corresponds to the first branchial arch is the trigeminus or fifth, and consequently these various muscles are supplied by it. The second arch has corresponding to it the seventh nerve, and its musculature is partly represented by the stylohyoid and posterior belly of the digastric and by the stapedius muscle of the middle ear. From the more superficial portions of the branchio- mere, however, a sheet of tissue arises which gradually extends upward and downward to form a thin covering for the entire head and neck, its lower portion giving rise to the platysma and the nuchal fascia which extends backward from the dorsal border of this muscle, while its upper parts become the occipito-frontalis and the superficial muscles of the face (the muscles of expression), together with the fasciae which unite the various muscles of this group. The extension of the platysma sheet of muscles over the face is well shown by the development of the branches of the facial nerve which supply it (Fig. 124). The degeneration of the upper part of the third arch produces a shifting forward of one of the muscles derived from its branchio- mere, the stylopharyngeus arising from the base of the styloid process. The innervation of this muscle by the ninth nerve indi- cates, however, its true significance, and since fibers of this nerve of the third arch also pass to the constrictor muscles of the pharynx, a portion of these must also be regarded as having arisen from the third branchiomere. The cartilages of the fourth and fifth arches enter into the formation of the larynx and the muscles of the corresponding branchiomeres constitute the muscles of the larynx, together with the remaining portions of the constrictors of the pharynx and the muscles of the soft palate, with the exception of the tensor. Both these arches have branches of the tenth nerve associated with them and hence this nerve supplies the muscles named. In addi- tion, two of the extrinsic muscles of the tongue, the glossopalatinus 14 2IO THE CRANIAL MUSCULATURE -3 a s Trapezius. Sterno- mastoid. H IhiiliiJiiiii 1- J, 2 « . 1 C/3 1 ' i hi 3 2 " s g. en o 3 H o a" 1 .2 ^ .2 > "a 2 S a: a '£ s pq 3 a THE LIMB MUSCLES 211 and chondroglossus, belong to the fourth or fifth branchiomere, although the remaining muscles of this physiological set are myo- tomic in origin. Finally, portions of two other muscles should probably be in- cluded in the list of branchiomeric muscles, these muscles being the trapezius and sternomastoid. It has already been seen that they are partly derived from the cervical myotomes, but they are also innervated in part by the spinal accessory, and since this nerve is really a special portion of the motor root of the vagus the muscles suppHed by it should be regarded as branchiomeric in origin. The table on p. 210 shows the relations of the various cranial muscles to the myotomes and branchiomeres, as well as to the motor cranial nerves. The Limb Muscles. — It has been customary to regard the hmb muscles as derivatives of certain of the myotomes, these structures in their growth ventrally in the trunk walls being supposed to pass out upon the postaxial surface of the limb buds and loop back again to the trunk along the praeaxial surface, each myotome thus giving rise to a portion of both the dorsal and the ventral muscu- lature of the limb. This view has not, however, been verified by direct observation of an actual looping of the myotomes over the axis of the limb buds; indeed, on the contrary, the limb muscles have been found to develop from the cores of mesenchyme which form the axes of the hmb buds and from which the Hmb skeleton is also developed, and, furthermore, these axial cores can be traced back to an origin from the unsegmented ventral mesoderm, the adjacent myotomes having apparently no part in their formation. It seems proper, therefore, to regard the Umb musculature as be- longing to a different embryological category from the axial myo- tomic muscles, just as was the case of the branchiomeric musculature . The strongest evidence in favor of a myotomic origin of the Hmb muscles is that furnished by their nerve supply, this present- ing a distinctly segmental arrangement. This does not necessarily imply, however, a corresponding primarily metameric arrangement of the muscles, any more than the pronouncedly segmental ar- rangement of the cutaneous nerves implies a primary metamerism 212 THE LIMB MUSCLES of the dermis (see p. 145). It may mean only that the nerves, being segmental, retain their segmental relations to one another even in their distribution to non-metameric structures, and that, consequently, the limb musculature is supplied in succession from one border of the limb bud to the other from succeeding nerve roots. From this segmentally arranged innervation it is possible to recognize in the limb buds a series of parallel bands of muscle (r.d &:v. ym Fig. 125. — Diagram of a Segment of the Body and Limb. hi. Axial blastema; dm, dorsal musculature of trunk; rl, nerve to limb; 5, septum between dorsal and ventral trunk musculature; sir. d, dorsal layer of limb muscula- ture; tr.d and tr.v, dorsal and ventral divisions of a spinal nerve; vm, ventral muscu- lature of the trunk. — (.Kollmann.) tissue, extending longitudinally along the bud and each supplied by a definite segmental nerve. And furthermore, corresponding to each band upon the ventral (praeaxial) surface of the Hmb bud, there is a band similarly innervated upon the dorsal (postaxial) surface, since the fibers which pass to the limb from each nerve root sooner or later arrange themselves in praeaxial and postaxial groups as is shown in the diagram Fig. 125. The first nerve which enters the Hmb bud lies along its anterior border, and consequently THE LIMB MUSCLES 213 the muscle bands which are supplied by it will, in the adult, lie along the outer side of the arm and along the inner side of the leg, in consequence of the rotation in opposite directions which the limbs undergo during development (see p. 104). Fig. 126. — External Surface of the Os Innominatum showing the Attach- ment OF Muscles and the Zones Supplied by the Various Nerves. 12, Twelfth thoracic nerve; / to V, lumbar nerves; i and 2, sacral nerves. — (,Bolk.) The first nerve which supphes the muscle attached to the dorsum of the ihum is the second lumbar, and following that there come successively from before backward the remaining lumbar 214 th6 limb muscles and the first and second sacral nerves. The arrangement of the muscle bands suppKed by these nerves and the muscles of the adult to which they contribute may be seen from Fig. 126. What is shown there is only the upper portions of the postaxial I8r Pig. 127. — Sections through (A) the Thigh and (B) 'the Calf showing THE Zones Supplied by the Nerves. The Nerves are Numbered in Con- tinuation with the Thoracic Series. — (A, afler Bolk.) bands, their lower portions extending downward on the anterior surface of the leg. Only the sacral bands, however, extend throughout the entire length of the Umb into the foot, the second lumbar band passing down only to about the middle of the thigh. THE LIMB MUSCLES 2l5 the third to about the knee, the fourth to about the middle of the crus and the fifth as far as the base of the fifth metatarsal bone, and the same is true of the corresponding praeaxial bands, which descend from the ventral surface of the os coxae (innominatum) along the inner and posterior surfaces of the leg to the same points. The first and second sacral bands can be traced into the foot, the first giving rise to the musculature of its inner side and the second to that of its outer side, the praeaxial bands forming the plantar musculature, while the postaxial ones are upon the dorsum of the foot as a result of the rotation which the limb has undergone. In a transverse section through a limb at any level all the muscle bands, both praeaxial and postaxial, which descend to that level will be cut and will lie in a definite succession from one border of the limb to the other, as is seen in Fig. 127. In the differentia- tion of the individual muscles which proceeds as the nerves extend from the trunk into the axial mesenchyme of the hmb, the muscle bands undergo modifications similar to those already described as occurring in the trunk myotomes. Thus, there has evidently been a longitudinal splitting of the original praeaxial muscle mass to form the various muscles of the back of the thigh; the soleus and gastrocnemius represent deep and superficial layers formed from the same bands by a horizontal (tangential) splitting; these same muscles contain a portion of the second sacral band which overlaps muscles composed only of higher bands; and the intermuscular septum between the peroneus brevis and the flexor hallucis longus represents a portion of the third sacral band which has degenerated into connective tissue. A similar arrangement occurs in the bands which are to be recognized in the musculature of the upper limb. These are sup- plied by the fourth, fifth, sixth, seventh and eighth cervical and the first thoracic nerves, and only those supphed by the eighth cervical and the first thoracic nerves extend as far as the tips of the fingers. The arrangement of the bands in the upper part of the brachium may be seen from Fig. 128, in connection with which it must be noted that the fourth cervical band does not extend down to the level at which the section is taken and that the 2l6 THE LIMB MUSCLES praeaxial band of the eighth cervical nerve and both the praeaxial and postaxial bands of the first thoracic are represented only by- connective tissue in this region. In another sense than the longitudinal one there is a division of the limb musculature into more or less definite areas, namely, in a transverse direction in accordance with the jointing of the skeleton. Thus, there may be recognized a group of muscles which pass from the axial skeleton to the limb girdle, another from the Umb girdle to the brachium or thigh, another from the brachium Pig. 128. — Section through the Upper Part of the Arm showing the Zones Supplied by the Nerves. 511 to 7», Ventral branches; sd to Sd, dorsal branches o£ the cervical nerves. — (Bolk.) or thigh to the antibrachium or crus, another from the anti- brachium or crus to the carpus or tarsus, and another from the carpus or tarsus to the digits. This transverse segmentation if it may be so termed is not, however, perfectly definite, many muscles, even in the lower vertebrates, passing over more than one joint, and in the mammalia, especially, it is further obscured by secondary migrations, by the partial degeneration of muscles and by an end to end union of primarily distinct muscles. The latissimus dorsi, serratus anterior and pectoral muscles are all examples of a process of migration as is shown by their iimervation from cervical nerves, as well as by the actual migration which has been traced in the developing embryo (Mall, Lewis). THE LIMB MUSCLES 21? In the lower limb evidences of migration may be seen in the femoral head of the biceps, comparative anatomy showing this to be a derivative of the gluteal set of muscles which has secondarily be- come attached to the femur and has associated itself with a prae- axial muscle to form a compound structure. An appearance of migration may also be produced by a muscle making a secondary attachment below its original origin or above the insertion and the upper or lower part, as the case may be, then degenerating into connective tissue. This has been the case with the peroneus longus, which, in the lower mammals, has a femoral origin, but has in man a new origin from the fibula, its upper portion being represented by the fibular lateral ligament of the knee-joint. So too the pectoralis minor is primarily inserted into the humerus, but it has made a secondary attachment to the coracoid process, its distal portion forming a coraco-humeral ligament. The comparative study of the flexor muscles of the anti- brachial and crural regions has yielded abundant evidence of ex- tensive modifications in the differentiation of the limb muscles. In the tailed amphibia these muscles are represented by a series of superposed layers, the most superficial of which arises from the humerus or femur, while the remaining ones take their origin from the ulna or fibula and are directed distally and laterally to be inserted either into the palmar or plantar aponeurosis, or, in the case of the deeper layers, into the radius (tibia) or carpus (tarsus). In the arm of the lower mammalia the deepest layer becomes the pronator quadratus, the lateral portions of the super- ficial layer are the flexor carpi ulnaris and the flexor carpi radialis, while the intervening layers, together with the median portion of the superficial one, assuming a more directly longitudinal direction, fuse to form a common flexor mass which acts on the digits through the palmar aponeurosis. From this latter structure and from the carpal and metacarpal bones five layers of palmar muscles take origin. The radial and ulnar portions of the most superficial of these become the flexor polUcis brevis and abductor pollicis brevis and the abductor quinti digiti, while the rest of the layer degenerates into connective tissue, forming tendons which 2l8 THE LIMB MUSCLES pass to the four ulnar digits. Gradually superficial portions of the antibrachial flexor mass separate off, carrying with them the layers of the palmar aponeurosis from which the tendons representing the superficial layer of the palmar muscles arise, and they form with these the flexor digitorum subhmis. The deeper layers of Pig. 129. — Transverse sections through (A) the forearm and (B) the hand show- ing the arrangement of the layers of the flexor muscles. The superficial layer is shaded horizontally, the second layer vertically, the third obliquely to the left, the fourth vertically, and the fifth obliquely to the right. AbM, abductor digiti quinti; AdP, adductor poUicis; BR, brachio-radialis ; ECD, extensor digtorum communis; ECU, extensor carpi ulnaris ; EI, extensor indicis; EMD, extensor digiti quinti; EMP, abductor polUcis longus; ERB, extensor carpi radialis brevis; FCR, flexor carpi radialis; FCU, flexor carpi ulnaris; FLP, flexor pollicis longus; FM, flexor digiti quinti brevis; FP, flexor digitorum profundus; FS, flexor digitorum sublimis; ID interossei dorsales; IV, interossei volares ; L, lumbricales; OM, opponens digiti quinti PL, palmaris longus; FT, pronator teres; R, radius; U, ulna; II-V, second to fifth metacarpal. of the antibrachial flexor mass become the flexor digitorum profundus and the flexor pollicis longus (Fig. 129, A), and retain their connection with the deeper layers of the palmar aponeurosis which form their tendons; and since the second layer of the palmar muscles takes origin from this portion of the aponeurosis it be- THE LIMB MUSCLES 219 comes the lumbrical muscles, arising from the profundus tendons (Fig. 129, B). The third layer of palmar muscles becomes the adductors of the digits, reduced in man to the adductor poUicis, while from the two deepest layers the interossei are developed. Of these the fourth layer consists primarily of a pair of shps cor- responding to each digit, while the fifth is represented by a series of muscles which extend obliquely across between adjacent meta- carpals. With these last muscles certain of the fourth layer slips Fig. 30. — Transverse sections through (.4) the crus and (B) the foot, showing the arrangement of the layers of the flexor muscles. The shading has the same sig- niiicance as in the preceding figure. AbH, abductor hallucis ; A bM, abductor minimi digiti; AdH, adductor hallucis; ELD, extensor longus digitorum; F, fibula; FBD flexor brevis digitorum ; FBi?, flexor brevis hallucis; FBM, flexor brevis minimi digiti; FLD, flexor longus digitorum; G, gastrocnemius; ID, interossei dorsales; IV, inter- ossei ventrales; L, lumbricales; P, plantaris; Pe, peroneus longus; Po, popliteus; 5, soleus; T, tibia; TA, tibialis anticus; TP, tibialis posticus; I-V, first to fifth meta- tarsal. unite to form the dorsal interossei, while the rest become the volar interossei. The modifications of the almost identical primary arrange- ment in the crus and foot are somewhat different. The super- ficial layer of the crural flexors becomes the gastrocnemius and plantaris (Fig. 30, A) and the deepest layer becomes the popliteus and the interosseous membrane. The second and third layers unite to form a common mass which is inserted into the deeper layers of the plantar aponeurosis and later differentiates into the soleus and the long digital flexor, the former shifting its insertion from the plantar aponeurosis to the os calcis, while the flexor 220 LITERATURE retains its connection with the deeper layers of the aponeurosis, these separating from the superficial layer to form the long flexor tendons. The fourth layer assumes a longitudinal direction and becomes the tibialis posterior and the flexor hallucis longus and partly retains its original obhque direction and its connection with the deep layers of the plantar aponeurosis, becoming the quadratus plantae. In the foot (Fig. 129, B) the superficial layer persists as muscular tissue, forming the abductors, the flexor digitorum brevis and the medial head of the flexor hallucis brevis, the second layer becomes the lumbricales, and the third the lateral head of , the flexor hallucis brevis and the abductor hallucis, while the fourth and fifth layers together form the interossei, as in the hand, the flexor quinti digiti brevis really belonging to that group of muscles. LITEEAIUKE C. R. Bardeen and W. H. Lewis: "Development of the Limbs, Body-wall, and Back in Man," The American Journal of Anal., i, igoi. K. Bardeleben: "Muskel und Fascia" Jenaische Zdtschr. fiir Naiurwissensch., XV, 1882. L. Bolk: "Beziehungen zwischen Skelett, Muskulatur und Nerven der Extremitaten, dargelegt am Beckengiirtel, an dessen Muskulatur sowie am Plexus lumbo- sacralis," Morphol. Jahrbuch, xxi, 1894. L. BoLKr " Rekonstruktion der Segmentirung der Gliedmassenmuskulatur dargelegt an den Muskeln des Oberschenkels und des Schultergiirtels," Morphol. Jahrhuch, xxn, 1895. L. Bolk: "Die Sklerozonie des Humerus," Morphol. Jahrbuch, xxm, 1896. L. Bolk: "Die Segmentaldifferenzierung des menschlichen Rumptes und seiner Extremitaten," i, Morphol. Jahrhuch. xxv, 1898. R. Futamura: "Ueber die Entwickelung der Facialismuskulatur des Menschen," Anat. Hefte, xxx, 1906. E. Godlewski: "Die Entwicklung des Skelet- und Herzmuskelgewebes der Sauge- thiere," Archivfiir mikr., Anat. lx, 1902. E. Grafenberg: "Die Entwicklung der menschlichen Beckenmuskulatur,'' Anat. Hefte, xxm, 1904. W. P. HERRnsfGHAM: "The Minute Anatomy of the Brachial Plexus," Proceedings of the Royal Soc. London, xli, 1886. W. H. Lewis: "The Development of the Arm in Man," Amer. Journ. of Anat., 1, 1902 J. B. MacCallum: "On the Histology and Histogenesis of the Heart Muscle-cell," Anat. Anzeiger, xin, 1897. J. B. MacCallum: "On the Histogenesis of the Striated Muscle-fiber and the Growth of the Human Sartorius Muscle," Johns Hopkins Hospital Bulletin, 1898. LITERATURE 221 F. P. Mall: "Development of the Ventral Abdominal Walls in Man," Journ. of Morphol., XIV, 1898. Caroline McGill: "The Histogenesis of Smooth Muscle in the Alimentary Canal and- Respiratory Tract of the Pig," Internal. Monatschr. Anat. und Phys., xxiv, 1907. J. P. McMurkich: "The Phylogeny of the Forearm Flexors," Amer. Journ. of Anat., n, 1903. J. P. McMurrich: "The Phylogeny of the Palmar Musculature," Amer. Journ. of Anat., n, 1903. J. P. McMurrich: "The Phylogeny of the Crural Flexors," Amer. Journ. of Anat. IV, 1904. J. P. McMurrich: "The Phylogeny of the Plantar Musculature," Amer. Journ. of Anat.yVi, 1907. A. Meek: "Preliminary Note on the Post-embryonal History of Striped Muscle- fibers in Mammalia," Anat. Anzeiger, xiv, 1898. (See also Anat. Anzeiger^xv, 1899.) B. Morpurgo: "Ueber die post-embryonale Entwickelung der quergestreiften Muskel von weissen Ratten," Anat. Anzeiger, xv, 1899. I. Popowsky: "Zur Entwicklungsgeschichte des N. facialis beim Menschen," Morphol. Jahrhuch, xxin, 1896. I. Popowsky: "Zur Entwickelungsgeschichte der Dammuskulatur beim Menschen," Anat. Hefte, xi, 1899. L. Rethi: "Der peripheren Verlauf der motorischen Rachen- und Gaumennerven," Sitzungsber. der hats. Akad. Wissensch. Wien. Math.-Naturwiss. Classe, cii, 1893. C. S. Sherrington: "Notes on the Arrangement of Some Motor Fibers in the Lumbo-sacral Plexus," Journal of Physiol., xin, 1892. J. B. Sutton: "Ligaments, their Nature and Morphology," London, 1897. CHAPTER IX THE DEVELOPMENT OF THE CIRCULATORY AND LYMPHATIC SYTEMS At present nothing is known as to the earliest stages of de- velopment of the circulatory system in the human embryo, but it may be supposed that they resemble in their fundamental fea- tures what has been observed in such forms as the rabbit and the chick. It will be convenient to consider first the development of the first blood-vessels and of the blood, and later the formation of the heart and principal blood-vessels. In the rabbit the extension of the mesoderm from the embryo- nic region, where it first appears, over the yolk-sac is a gradual process, and it is in the more peripheral portions of the layer that the blood-vessels first make their appearance. They can be dis- tinguished before the sphtting of the mesoderm has been com- pleted, but are always developed in that portion of the layer which is most intimately associated with the yolk-sac, and conse- quently becomes the splanchnic layer. They belong, indeed, to the deeper portion of that layer, that nearest the endoderm of the yolk-sac, and so characteristic is their origin from this portion of the layer that it has been termed the angioblast and has been held to be derived from the endoderm independently of the meso- derm proper. The first indication of blood-vessels is the appear- ance in the peripheral portion of the mesoderm of cords or minute patches of spherical cells (Fig. 131, A). These increase in size by the division and separation of the cells from one another (Fig. 131, B), a clear fluid appearing in the intervals which separate them. Soon the cells surrounding each cord arrange themselves to form an enclosing wall, and the cords, increasing in size, unite together to form a network of vessels in which float the spherical cells which may be known as haemohlasts. Viewed from the sur- DEVELOPMENT Or THE BLOOD VESSELS 223 face at this stage a portion of the vascular area of the mesoderm would have the appearance shown in Fig. 132, revealing a dense network of canals in which, at intervals, are groups of haemo- blasts adherent to the walls, constituting what have been termed the blood-islands, while in the meshes of the network unaltered mesoderm cells can be seen, forming the so-called substance-islands. Two views obtain as to the way in which the extension of the vascularization process from the extra embryonic-regions into the body of the embryo takes place. In one the angioblast is given Fig. 131. — Transverse Sections through the Area Vasculosa of Rabbit Embryos showing the Transformation of Mesoderm Cells into the Vascular Cords. Ec, Ectoderm; En, endoderm; Me, mesoderm. — (van der Slricht.) the status of an additional germ-layer, distinct from the mesoderm; it is a specific tissue, set apart at an early stage of the develop- ment as the origin of all the vascular apparatus, endothelium and blood elements, of the embryo, and it is the sole source of this apparatus. Hence the vapnilar tis.sue of the, embrvo proper is f^^i-m Pfl by the extension into the embryo of angiobla stic material f rom the j xlra-pmhrvonic regions, the vascular endothelium is a spe cific tissue and the embryonic mesenchyme has no part in its f ormation^ According to the other view such specificity is denied the angioblast and it is held that vasifactive tissue mav be formed inrall y from th e-£mbrvoni c mesenchvme^ the angioblast is merely 224 DEVELOPMENT OF THE BLOOD VESSELS extra-embryonic mesenrhym^ that has assumed a vasifactive fiinc- tion, and by processes similar to those shown by it the mesenchyme of practically any part of the embryo proper may become con- verted into vascular tissue, producing vascular networks which eventually unite directly or in- directly with those formed by the angioblast. Briefly, according to this view, there is not neces- sarily immediate genetic contin- uity of all the vascular endothe- lium, but mesenchyme cells in any region of the body may become endothelium and conversely en- dotheHal cells under certain condi- tions may revert to mesenchyme. Whichever of these views eventually proves to be correct the end result is that the blood 1 vascular system, both in its em-j bryonic and extra-embryonic por- tions, consists in its earlier stagesi of a continuous network of vessels! h ned with endotheUum and con- taining haemoblasts formed by the multiplication of the original haemoblasts and by proliferation from the endothehal cells them- selves. Later, enlargements of the network develop along more or less definite lines to form the heart, the arteries and veins, other portions of it persist to form the capillaries, while others again disappear entirely. The differentiation of blood-vessels from the network on the surface of the yolk-sac of a rabbit embryo is shown at its commencement in Fig. 133, A and in Fig. 133, B.the exten- sion of the differentiation has resulted in the formation of a sinus terminalis, a vitelline artery and two vitelline veins. Pig. 132. — Surface View of a Portion of the Area Vasculosa OF a Chick. The vascular network is represented by the shaded portion. Bi, Blood- island; Si, substance-island. — (Disse.) DEVELOPMENT OF THE BLOOD VESSELS 225 In the human embryo the slight development of the yolk-sac and the increased importance of the chorion in the nutrition of the embryo have apparently led to a reduction in the development of the viteUine network and an acceleration in the development of the chorionic vessels (see p. 118), but otherwise the early develop- ment of the blood-vascular system is probably similar to what has been described for the rabbit. ,, -;*-^'^'*i»*j(.^^'.:>^ ^ ..„^iiU#t. — ^^.''A Fig. 133. — The Vascular Areas of Rabbit Embryos. In B the Veins are Represented by Black and the Network is Omitted. — {von Beneden and Julin.) It is to be noted that the capillary network of the area vascu- losa consists of relatively wide anastomosing spaces whose endo- theUal lining rests directly upon the substance islands (Fig. 131). In certain of the embryonic organs, notably the hver, the meta- nephros and the heart, when these have become vascularized, the network has a similar character, consisting of wide anastomos- ing spaces bounded by an endothelium which rests directly, or almost so, upon the parenchyma of the organ (the hepatic cylin- ders, the mesonephric tubules, or the cardiac muscle trabeculse) (Figs. 134 and 191, B). To this form of capillary the term sinusoid has been applied (Minot), and it appears to be formed by the expansion of the wall of a previously existing blood-vessel, which thus moulds itself, as it were, over the parenchyma of the organ. IS 226 THE FORMATION OF THE BLOOD The true capillaries, on the other hand, are more definitely tubular in form, are usually imbedded in mesenchymatous connective tissue, but are developed in the same manner as the primary capillaries of the area vasculosa, by the aggregation of vasifactive cells to form cords, and the subsequent hollowing out of these. The Formation of the Blood.^The haemoblasts, which are the first formed blood-corpuscles are all nucleated and destitute or nearly so of haemoglobin. They have been held by some observers to be the only source of the various forms of corpuscles that are found in the adult vessels, while others maintain that they give rise only to the red corpuscles, the leukocytes arising in tissues external to the blood-vessels and only secondarily making their way into them. According to this latter view the red and white corpuscles have a different origin and remain distinct throughout life. However this may be, it is certain that the hsmoblasts and the erythrocytes that are formed from them increase by division in the interior of the embryo, and that there are certain portions of the body in which these divisions take place most abundantly, partly, perhaps, on account of the more favorable conditions of nutrition which they present and partly because they are regions where the circulation is sluggish and permits the accumulation of erythro- cytes. These regions constitute what have been termed the hematopoietic organs, and are especially noticeable in the later stages of fetal life, diminishing in number and variety about the time of birth. It must be remembered, however, that the life of individual corpuscles is comparatively short, their death and disintegration taking place continually during the entire life of the individual, so that there is a necessity for the formation of new corpuscles and for the existence of haematopoietic organs at all stages of life. In the fetus haemoblasts in process of division may be found in the general circulation and even in the heart itself, but they are much more plentiful in places where the blood-pressure is diminished, as, for instance, in the larger capillaries of the lower Limbs and in the capillaries of all the visceral organs and of the THE FORMATION OF THE BLOOD 227 subcutaneous tissues. Certain organs, however, such as the liver, the spleen, and the bone-marrow, present especially favorable conditions for the multiplication of the blood-cells, and in these not only are the capillaries enlarged, so as to aiford resting-places for the corpuscles, but gaps appear in the walls of the vessels through which the blood-elements may pass and so come into intimate relations with the actual tissues of the organs (Fig. 134). After birth the haematopoietic function of the liver ceases and that of the spleen becomes limited to the formation of white corpuscles though the complete function may be re-established in cases of extreme anaemia. The bone- marrow, however, retains the function completely, being throughout life the seat of for- mation of both red and white corpuscles, the lymphatic nodes and folhcles, as well as the spleen, assisting in the for- mation of the latter elements. The haembblasts early be- come converted into nucleated red corpuscles or erythrocytes by the development of haemo- globin in their cytoplasm, their nuclei at the same time becom- ing granular. Up to a stage at which the embryo has a are the only form of Fig. 134. — Section of a Portion of the LrvER of a Rabbit Embryo of s mm. e, Erythrocytes in the liver substance and in a capillary; h, hepatic cells. — (van der Stricht.) length of about 112 mm. these red corpuscle in the circulation, but at this time (Minot) a new form, characterized by its smaller size and more deeply staining nucleus, makes its appearance. These erythrocytes have been termed normoblasts (Ehrlich), although they are merely transition stages leading to the forma- tion of erythroplastids by the extrusion of their nuclei (Fig. 135). The cast-off nuclei undergo degeneration and phagocytic absorp- tion by the leukcocytes, and the masses of cytoplasm pass into 228 THE FORMATION OF THE BLOOD the circulation, becoming more and more numerous as develop- ment proceeds, until finally they are the typical haemoglobin- containing elements in the blood and form what are properly termed the red blood-corpuscles. It has already (p. 226) been pointed out that discrepant views prevail as to the origin of the white blood-corpuscles. Indeed, three distinct modes of origin have been assigned to them. According to one view they have a common origin with the erythrocytes from the hsemoblasts (Weidenreich), according to another they are formed from mesenchyme cells out- side the cavities of the blood-vessels (Maximow), while according to a third view the first formed leukocytes take their origin from the endodermal epitheHal cells of the thymus gland (Prenant). Fig. 13s. — Stages in the Transformation of an Erythro- cyte INTO AN ErYTHROPLASTID. (van der Stricht.) b ^^'r^Ss^ '/i£t^m^fm2A Fig. 136, — Figures of the Different Forms of White Corpuscles occurring IN Human Blood. a. Lymphocytes; 6, finely granular (neutrophile) leukocyte; c, coarsely granu- lar (eosinophile) leukocyte; d, polymorphonuclear (basophile) leukocyte.— (Weirfen- reich.) But whatever may be their origin, in later stages the leukocytes multiply by mitosis and there is a tendency for the dividing cells to collect in the lymphoid tissues, such a,s the lymph nodes, tonsils, THE FORMATION OF THE BLOOD 229 etc., to form more or less definite groups which have been termed germ-centers (Flemming). The new cells when they first pass into the circulation have a relatively large nucleus surrounded by a small amount of cytoplasm without granules and, since they re- semble the cells found in the lymphatic vessels, are termed lymphocytes (Fig. 136, a). In the circulation, however, other forms of leukocytes also occur, which are believed to have their origin from cells with much larger nuclei and more abundant cytoplasm, which occur throughout life in the bone-marrow and Fig. 137. M EGACARYOCYTE FROM A KiTTEN, WHICH HAS EXTENDED TwO PSEUDOPODIAL PROCESSES THROUGH THE WALL OF BlOOD-VESSEL AND IS BUDDING OFF Blood-platelets. hp. Blood-platelets; V, blood-vessel. — (J. H. Wright.) have been termed myelocytes. Cells of a similar type, free in the circulation, constitute what are termed the finely granular leuko- cytes (neutrophile cells of Ehrlich) (Fig. 135, b), but whether these and the myelocytes are derived from lymphocytes or have an independent origin is as yet undetermined. Less abundant are the coarsely granular leukocytes {eosinophile cells of Ehrlich) Fig. 136, c), characterized by the coarseness and staining reactions of their cytoplasmic granules and by their reniform or constricted nucleus. They are probably derivatives of the finely granular t)^e and it h£is been maintained by Weidemeich that their granules have been acquired by the phagocytosis of degenerated 230 THE FORMATION OF THE HEART erythrocytes. Finally, a third type is formed by the poly- morphonuclear or polynuclear leukocytes {basophile cells of Ehrlich) (Fig. 136, d), which are to be regarded as leukocytes in the process of degeneration and are characterized by their irregularly lobed or fragmented nuclei, as well as by their staining peculiarities. In the fetal haematopoietic organs and in the bone-marrow of the adult large, so-called giant-cells are found, which, although they do not enter into the general circulation, are yet associated with the development of the blood-corpuscles. These giant-cells as they occur in the bone-marrow are of two kinds which seem to be quite distinct, although both are probably formed from leukocytes. In one kind the cytoplasm contains several nuclei, whence they have been termed polycaryocytes, and they seem to be the cells which have already been mentioned as osteoclasts (p. 160). In the other kind (Fig. 137) the nucleus is single, but it is large and irregular in shape, frequently appearing as if it were producing buds. These megacaryocytes appear to be phagocytic cells, having as their function the destruction of degenerated corpuscles and of the nuclei of the erythrocytes. The blood-platelets have recently been shown by Wright to be formed from the cytoplasm of the megacaryocytes, by the constric- tion and separation of portions of the slender processes to which they give rise in their amoeboid movements (Fig. 137). They have also been described as forming in a similar manner from leukocytes and even from the endothelial cells of the blood vessels (Jordan). The Formation of the Heart. — The heart makes its appearance while the embryo is still spread out upon the surface of the yolk sac, and arises as two separate portions which only later come into contact in the median Hne. On each side of the body near the margins of the embryonic area a fold of the splanchnopleure appears, projecting into the coelomic cavity, and within this fold is a thin-walled sac, probably representing an enlargement of the primitive angioblastic network (Fig. 138, A). Each fold will produce a portion of the muscular walls {myocardium) of the heart andeach sac part of its endothelium (endocardium). As the THE FOKMATION OF THE HEART 231 constriction of the embryo from the yolk-sac proceeds, the two folds are gradually brought nearer together (Fig. 137, B), until they meet in the mid-ventral line, when the myocardial folds and am A 'erv Fig. 138. — Diagrams Illustrating the Formation of the Heart in the Guinea- pig. • The mesoderm is represented in black and the endocardium by a broken line, am. Amnion; en, endoderm; h, heart; i, digestive tract. — {After Strahl and Carius.) endocardial sacs fuse together (Fig. 136, C) to form a cylindrical heart lying in the mid-ventral Une of the body, in front of the anterior surface of the yolk-sac and in what will later be the 232 THE FORMATION OF THE HEART cervical region of the body. At an early stage the various veins which have already been formed, the vitellines, umbilicals, jugu- lars and cardinals, unite together to open into a sac- like structure, the sinus venosus, and this opens into the posterior end of the heart cylinder. The anterior end of the cylinder tapers off to form the aortic bulb, which is continued forward on the ventral surface of the pharyngeal region and carries the blood away from the heart. The blood accordingly opens into the posterior end of the heart tube and flows from its anterior end. Fig. 139. — Heart of Embryo of 2.15 MM., FROM A Reconstruction. a. Atrium; ab, aortic bulb;''d, dia- phragm; dc, ductus Cuvieri; I, liver; !i, ventricle; vj, jugular vein; vu, um- bilical vein. — (His.) Pig. 140. — Heart of Embryo of 4.2 mm., seen from the dorsal Surface. DC, Ductus Cuvieri; lA, left atrium; rA, right atrium; vj, jugular vein; VI, left ventricle; vu, umbilical vein. — (His.) The simple cylindrical form soon changes, however, the heart tube in embryos of 2.15 mm. in length having become bent upon itself into a somewhat S-shaped curve (Fig. 139). Dorsally and to the left is the end into which the sinus venosus opens, and from this the heart tube ascends somewhat and then bends so as to pass at first ventrally and then caudally and to the right, where it again bends at first dorsally and then anteriorly to pass over into THE FORMATION OF THE HEART 233 the aortic bulb. The portion of the curve which lies dorsally and to the left is destined to give rise to both atria, the portion which passes from right to left represents the future left ventricle, while the succeeding portion represents the right ventricle. In later stages (Fig. 140) the left ventricular portion drops down- ward in front of the atrial portion, assuming a more horizontal position, while the portion which represents the right ventricle is drawn forward so as to lie in the same plane as the left. At the same time two small out-pouchings develop from the atrial part of the heart and form the first indications of the two atria. As development pro- gresses, these increase in size to form large pouches opening into a common atrial canal (Fig. 141) which is directly continuous with the left ventricle, and as the enlargement of the pouches con- tinues their openings into the canal enlarge, until finally the pouches become continuous with one another, forming a single large sac, and the atrial canal becomes reduced to a short tube which is slightly invaginated into the ventricle (Fig. 142). In the meantime the sinus venosus, which was originally an oval sac and opened into the atrial canal, has elongated trans- versely until it has assumed the form of a crescent whose convexity is in contract with the walls of the atria, and its opening into the heart has verged toward the right, until it is situated entirely within the area of the right atrium. As the enlargement of the atria continues, the right horn and median portion of the crescent are gradually taken up into their walls, so that the various veins which originally opened into the sinus now open directly into the right atrium by a single opening (Fig. 143) guarded on either side by a projecting fold, these folds being continued upon the roof Fig. 141. — Heart of Embryo of 5 MM., Seen from in Front and slightly FROM Above. — (His.) 234 THE FORMATION OF THE HEART of the atrium as a muscular ridge, known as the septum spurium (Fig. 42, sp). The left horn of the crescent is not taken up into the atrial wall, but remains upon its posterior surface as an elon- gated sac, forming the coronary sinus. * The division of the now practically single atrial cavity into the permanent right and left atria begins with the formation of a falciform ridge running dorso-ventrally across the roof of the cavity. This is the atrial septum or septum primum (Fig; 142 Fig. 142. — Inner Surface of the Heart of an Embryo of io mm. al, Atrio-venticular thickening; sp, septum spurium; ss, septum primum; sv, septum ventriculi; ve, Eustachian valve. — {His.) ss), and it rapidly increases in size and thickens upon its free margin, which reaches almost to the upper border of the short atrial canal (Fig. 144). The continuity of the two atria is thus almost dissolved, but is soon re-estabUshed by the formation in the dorsal part of the septum of an opening which soon reaches a considerable size and is known as the foramen ovale (Fig. 143, /o). Close to the atrial septum, and parallel with it, a second ridge ap- pears in the roof and ventral wall of the right atrium. This septum secundum (Fig. 143, 5') is of relatively slight development THE FORMATION OF THE HEART 23 s in the human embryo, and its. free edge, arching around the ventral edge and floor of the foramen ovale, becomes continuous with the left Up of the fold which guards the opening of the sinus venosus and with this forms the annulus of Vieussens of the adult heart. When the absorption of the sinus venosus into the wall of the right atrium has proceeded so far that the veins communicate directly with the atrium, the vena cava superior opens into it at Sr Sz, the upper part of the dorsal wall, the vena cava inferior more laterally, and below this is the smaller opening of the coronary sinus. The upper portion of the right lip of the fold which originally surrounded the opening of the sinus venosus, together with the septum spurium, gradually disappears ; the lower portion persists, however, and forms (i) the Eustachian valve (Fig. 143, Ve), guarding the opening of the inferior cava and directing the blood entering by it toward the foramen ovale, and (2) the Thebesian valve, which guards the open- ing of the coronary sinus. At first no veins communicate with the left atrium, but on the development of the lungs and the establishment of their vessels, the pulmonary veins make connection with it. Two veins arise from each lung, and as they pass toward the heart they unite in pairs, the two vessels so formed again uniting to form a single short trunk which opens into the upper part, of the atrium (Fig. 144, Vep). As is the case with the right atrium and the sinus venosus, the expansion of the left atrium brings about the absorption of the short single trunk into its walls, and, the expansion continuing, the two vessels are also absorbed, so that eventaully the four pri- mary veins open independently into the atrium. While the atrial septa have been developing there has appeared Fig. 143. — Heart of Em- bryo OF 10.2 CM. FROM WHICH Half of the Right Auricle HAS BEEN Removed /o. Foramen ovale; pa, pulmonary artery; 5i septum primum; S2, septum sec- undum; Sa, systemic aorta; V, right ventricle; vci and vcs, inferior and superior venee cavEe; Ve, Eustachian valve. 236 THE FORMATION OF THE HEART on the dorsal wall of the atrial canal a tubercle-like thickening of the endocardium, and a similar thickening also forms on the ventral wall. These endocardial cushions increase in size and finally unite together by their tips, forming a complete parti- tion, dividing the atrial canal into a right and left half (Fig. 144). En.s Bw'' Fig. 144. — Section through a Reconstruction of the Heart of a Rabbit Embryo of io.i mm. Ad and Adi, Right and As, left atrium; Bwi and Bwi, lower ends of the ridges which divide the aortic bulb; En, endocardial cushion; En.r and En.s, thickenings of the cushion; la, interatrial and Iv, interventricular communication; Si, septum primum; Sd, right and Ss, left horn of the sinus venosus; S.iv, ventricular septum; SM, opening of the sinus venosus into the atrium; Vd, right and Vs, left ventricle; Vej, jugular vein; Vep, pulmonary vein; Vvd and Vvs, right and left limbs of the valve guarding the openings of the sinus venosus. — (Born.) With the upper edge of this partition the thickened lower edge of the atrial septum unites, so that the separation of the atria would be complete were it not for the foramen ovale. While these changes have been taking place in the atrial por- THE FORMATION OF THE HEART 237 tion of the heart, the separation of the right and left ventricles has also been progressing, and in this two distinct septa take part. From the floor of the ventricular cavity along the line of junction of the right and left portions a ridge, composed largely of muscular tissue, arises (Figs. 142 and 144), and, growing more rapidly in its dorsal than its ventral portion, it comes into contact and fuses with the dorsal part of the partition of the atrial canal. Ventrally, however, the ridge, known as the venrficular septum, fails to reach the ventral part of the partition, so that an oval foramen, situated just below the point where the aortic bulb arises, still remains between the two ventricles. This opening is finally closed by what is termed the aortic septum. This makes its appearance in the aortic bulb just at the point where the first lateral branches which give origin to the pulmonary arteries (see p. 245) arise, and is formed by the fusion of the free edges of two endocardial ridges which develop on opposite sides of the bulb. From its point of origin it gradually extends down the bulb until it reaches the ventricle, where it fuses with the free edge of the ventricular septum and so completes the separation of the two ventricles (Fig. 145). The bulb now consists of two vessels lying side by side, and owing to the position of the partition at its anterior end, one of these vessels, that which opens into the right ventricle, is continuous with the pulmonary arteries, while the other, which opens into the left ventricle, is continuous with the rest of the vessels which arise from the forward continuation of the bulb. As soon as the development of the partition is com- pleted, two grooves, corresponding in position to the lines of at- tachment of the partition on the inside of the bulb, make their appearance on the outside and gradually deepen until they finally meet and divide the bulb into two separate vessels, one of which is the pulmonary aorta and the other the systemic aorta. In the early stages of the heart's development the muscle bundles which compose the wall of the ventricle are very bosely arranged, so that the ventricle is a somewhat spongy mass of muscular tissue with a relatively small cavity. As development proceeds the buncjles nearest the outer surface come closer to- 238 THE FORMATION OF THE HEART gether and form a compact layer, those on the inner surface, how- ever, retaining their loose arrangement for a longer time (Fig. T:a?:d S.ivr Fig. 145. — Diagrams of Sections through the Heart of Embryo Rabbits TO Show the Mode of Division of the Ventricles and of the Atrio-ventricu- LAR Orifice. Ao, Aorta; Ar.p, pulmonary artery; B, aortic bulb; Bw^ and *, one of the ridges which divide the bulb; Eo, and Eu, upper and lower thickenings of the margins of the atrio-ventricular orifice; F.av.c, the original atrio-ventricular orifice; F.av.d and F.av.s, right and left atrio-ventricular orifices; Oi, interventricular communication; 5. ill, ventricular septum; Vd and Vs, right and left ventricles. — {Born.) 144). The lower edge of the atrial canal becomes prolonged on the left side into one, and on the right side into two, flaps which project downward into the ventricular cavity, and an additional THE FORMATION OF THE HEART 239 flap arises on each side from the lower edge of the partition of the atrial canal, so that three flaps occur in the right atrio-ven- tricular opening and two in the left. To the under surfaces of these flaps the loosely arranged muscular trabeculae of the ventricle are attached, and muscular tissue also occurs in the flaps. This condition is transitory, however; the muscular tissue of the flaps degenerates to form a dense layer of connective tissue, and at the same time the muscular trabeculae undergo a condensation. Some of them separate from the flaps, which represent the atrio-ventricu- lar valves, and form muscle bundles which may fuse throughout their entire length with the more compact portions of the ventricu- PiG. 146. — Diagrams showing the Development of the Auriculo-ventricular Valves. b. Muscular trabeculae; cM, chordae tendineae; mk and mk^, valve; pm, musculus papillaris; tc, trabeculae carneae; v, ventricle. — (From Hertwig, after Gegenbaur.) lar walls, or else may be attached only by their ends, forming loops; these two varieties of muscle bundles constitute the ira- beculcB carnea of the adult heart. Other bundles may retain a transverse direction, passing across the ventricular cavity and forming the so-called moderator hands; while others, again, re- taining their attachment to the valves, condense only at their lower ends to form the musculi papillares, their upper portions undergoing conversion into strong though slender fibrous cords, the chorda tendinea (Fig. 146). The endocardial Uning of the ventricles is at first a simple sac separated by a distinct interval from the myocardium, but when the condensation of the muscle trabeculae occurs the endocardium applies itself closely to the irregular surface so formed, dipping 240 THE FORMATION OP THE HEAKT into all the crevices between the trabeculae carneae and wrapping itself around the musculi papillares and chordae tendinae so as to form a complete lining of the inner surface of the myocardium. In early stages the myocardial tissue of the atria is continuous with that of the ventricles throughout the entire circumference of the wall of the atrial canal, but later this wall becomes converted into connective tissue and the continuity is interrupted, except in the region behind the posterior endocardial cushion. Here a band of the original tissue persists and eventually forms the atrio-ventricular bundle. The aortic and pulmonary semilunar valves make their appearance, before the aortic bulb undergoes its longitudinal split- ting, as four tubercle-like thickenings of con- Dective tissue situated on the inner wall of the bulb just where it arises from the ventricle. When the division of the bulb occurs, two of the thickenings, situated on opposite sides, are divided, so that both the pulmonary and systemic aortae receive three thickenings (Fig. 147). Later the thickenings "become hollowed out on the surfaces directed away from the ventricles and are so converted into the pouch-Uke valves of the adult. Changes in the Heart after Birth. — The heart when first formed Mes far forward in the neck region of the embryo, between the head and the anterior surface of the yolk-sac, and from this posi- tion it gradually recedes until it reaches its final position in the thorax. And not only does it thus change its relative position, but the direction of its axes also changes. For at an early stage the ventricles lie directly in front of {i.e., ventrad to) the atria and not below them as in the adult heart, and this primitive condition is retained until the diaphragm has reached its final position (see P- 325)- In addition to these changes in position, which are antenatal, important changes also occur in the atrial septum after birth. Throughout the entire period of fetal life the foramen ovale Pig. 147. — Dia- grams Illustrating the pormation of the Semilunar Valves. — (pegenbaur.) DEVELOPMENT OF THE ARTERIAL SYSTfeM 241 persists, permitting the blood returning from the placenta and entering the right atrium to pass directly across to the left atrium, thence to the left ventricle, and so out to the body through the systemic aorta (see p. 268). At birth the lungs begin to function and the placental circulation is cut off, so that the right atrium receives only venous blood and the left only arterial; a persistence of the foramen ovale beyond this period would be injurious, since it would permit of a mixtue of the arterial and venous bloods, and, consequently, it closes completely soon after birth. The closure is made possible by the fact that during the growth of the heart in size the portion of the atrial septum which is between the edge of the foramen ovale and the dorsal wall of the atrium increases in width, so that the foramen is carried further and further away from the dorsal wall of the atrium and comes to be almost com- pletely overlapped by the annulus of Vieussens (Fig. 143). This process continuing, the dorsal portion of the atrial septum finally overlaps the free edge of the annulus, and after birth the fusion of the overlapping surfaces takes place and the foramen is com- pletely closed. In a large percentage (25 to 30 per cent.) of individuals the fusion of the surfaces of the septum and annulus is not complete, so that a slit- like opening persists between the two atria. This, however, does not allow of any mingling of the blood in the two cavities, since when the atria contract- the pressure of the blood on both sides will force the overlapping folds together and so practically close the opening. Occa- sionally the growth of the dorsal portion of the septum is imperfect or is inhibited, in which case closure of the foramen ovale is impossible. The Development of the Arterial Systeni.^It has been seen (p. 222) that the formation of the blood-vessels begins in the extra- embryonic splanchnic mesoderm surrounding the yolk-sac and ex- tends thence toward the embryo. Furthermore, it has been seen that the vessels appear as capillary networks from which definite stems are later elaborated. This seems also to be the method of formation of the vessels developed within the body of the embryo, the arterial and venous stems being first represented by a number of anastomosing capillaries, from which, by the enlargement of 16 242 DEVELOPMENT OF THE ARTERIAL SYSTEM some and the disappearance of the others, the definite stems are formed. The earliest known embryo that shows a blood circulation is that described by Eternod (Fig. 44). From the plexus of vessels on the yolk-sac two veins arise which unite with two other veins returning from the chorion by the belly-stalk and passing forward to the heart as the two umbiUcal veins (Fig. 148, Vu). There is as yet no vitelline vein, the chorionic circulation in the human Fig. 148. — Diagram showing the Arrangement of the Blood-vessels in an Embryo ±.3 mm. in Length. Au, Umbilical artery; AH, allantois; Ch, chorionic villus; dAr and dAs, right and left dorsal aortae; Vu, umbilical veins; Ys, yolk-sac. — (From Kallmann after Eternod.) embryo apparently taking precedence over the vitelline. From the heart a short arterial stem arises, which soon divides so as to form three branches* passing dorsally on either side of the phar- ynx. The branches of each side then unite to form a paired dorsal * Evans (Keibel-Mall, Human Embryology, Vol. 11, 191 2) considers two of these branches to be probably plexus formations rather than definite stems, since there is evidence to indicate that only one such stem exists at such an early stage of development. DEVELOPMENT OF THE ARTERIAL SYSTEM 243 aorta {dAr, dAs) which extends caudally and is continued into the belly-stalk and so to the chorion as the umbilical arteries (Au). There is as yet no sign of vitelline arteries passing to the yolk-sac, again an indication of the subservience of the vitelline to the chorionic circulation in the human embryo. In later stages when the branchial arches have appeared the dorsally directed arteries are seen to he in these, forming what are termed the branchial arch vessels, and later also the two dorsal aortse fuse as far forward as the region of the eighth cervical segment to form a single trunk from which segmental branches arise. It will be convenient to con- sider first the history of the ves- sels which pass dorsally in the branchial arches. Altogether, six of these vessels are devel- oped, the fifth rudimentary and transitory, and when fully formed they have an arrangement which may be understood from the dia- gram (Fig. 149). This arrange- ment represents a condition which is permanent in the lower verte- brates. In the fishes the respiration is performed by means of gills developed upon the branchial arches, and the heart is an organ which receives venous blood from the body and pumps it to the gills, in which it becomes arterialized and is then collected into the dorsal aortas, which distribute it to the body. But in terrestrial animals,' with the loss of gills and the development of the lungs as respiratory organs, the capillaries of the gills disappear and the afferent and efferent branchial vessels become continuous, the condition represented in the diagram resulting. Fig. 149. — Diagram Illustrating THE Primary Arrangement of the Branchial Arch Vessels. a, Aorta; ab, aortic bulb; ec, external carotid; ic, internal carotid; sc, sub- clavian; I— VI, branchial arch vessels. 244 DEVELOPMENT OF THE ARTERIAL SYSTEM But this condition is merely temporary in the mammalia and numerous changes occur in the arrangement of the vessels before the adult plan is realized. The first change is a disappearance of the vessels of the first arch, the ventral stem from which it arose being continued forward to form the temporal arteries, giving off near the point where the branchial vessel originally arose a branch which represents the internal maxillary artery in part, and possibly also a second branch which represents the external maxillary (His). A little later the second branchial vessel also degenerates (Fig. Pig. 150. — Arterial System op an Embryo of 10 mm. Ic, Internal carotid; P, pulmonary artery; Ve, vertebral artery; III to, VI, persistent branchial vessels. — (His.) 150), a branch arising from the ventral trunk near its former origin, possibly representing the future lingual artery (His), and then the portion of the dorsal trunk which intervenes between the third and fourth branchial vessels vanishes, so that the dorsal trunk anterior to the third branchial arch is cut off from its con- nection with the dorsal aorta and forms, together with the vessel of the third arch, the internal carotid, while the ventral trunk, anterior to the point of origin of the third vessel, becomes the external carotid, and the portion which intervenes between the third and fourth vessels becomes the common carotid (Fig. 151). The rudimentary fifth vessel, like the first and second, dis- DEVELOPMENT OF THE ARTERIAL SYSTEM 245 appears, but the fourth persists to form the aortic arch, there being at this stage of development two complete aortic arches. From the sixth vessel a branch arises which passes backward to unite with a network of vessels which extends downwards to the region of the lungs and is formed in cat embryos by the an- ^^ astomosis of branches from the upper six segmental branches of the dorsal aortae (Huntington). From this network the pulmonary artery eventually differen- tiates and, its connections with the segmental aortic branches dissolving, it ap- pears to be a direct down- growth from the sixth arch. The portion of the right sixth arch that intervenes between the point of origin of the pulmonary artery and the right aortic arch disap- pears, while the correspond- ing portion of the left side persists until after birth, forming the ductus arteriosus {ductus Botalli) (Fig. 151). When the longitudinal di- vision of the aortic bulb occurs (p. 237), the septum is so arranged as to place the sixth arch in communication with the right ventricle and the remain- ing vessels in connection with the left ventricle, the only direct communication between the systemic and pulmonary vessels being by way of the ductus arteriosus, whose significance will be explained later (p. 269). One other change is still necessary before the vessels acquire Fig. 151. — -Diagram Illustrating the Changes in the Branchial Arch Vessels. a. Aorta; da, ductus arteriosus; ec, ex- ternal carotid; ic, internal carotid; pa, pulmonary artery; sc, subclavian; I— IV, aortic arch vessels. 246 DEVELOPMENT OF THE ARTERIAL SYSTEM the arrangement which they possess during fetal life, and this consists in the disappearance of the lower portion of the right aortic arch (Fig. 151), so that the left arch alone forms the con- nection between the heart and the dorsal aorta. The upper part of the right aortic arch persists to form the proximal part of the right subclavian artery, the por- tion of the ventral trunk which unites the arch with the aortic bulb becoming the innominate artery. From the entire length of the thoracic aorta, and in the embryo from the aortic arches, lateral branches arise corresponding to each segment and accompanying the segmental nerves. The first of these branches arises just be- low the point of union of the vessel of the sixth arch with the dorsal trunk and accompanies the hypoglossal nerve (Fig. 152, K), and that which accom- panies the seventh cervical nerve arises just above the point of union of the two aortic arches (Fig. 152, s), and extends out into the limb bud, forming the subclavian artery.* Further down twelve pairs of lateral branches, arising from the thoracic portion of the aorta, represent the intercostal arteries, and still lower four pairs of lumbar arteries are formed, the fifth lumbars being represented by two large branches, the common * It must be remembered that the right subclavian of the adult is more than equivalent to the left, since it represents the fourth branchial vessel + a portion of the dorsal longitudinal trunk -|- the lateral segmental branch (see Fig. 144). in DC iCo. IM Pig. 152. — Diagram showing the Relations of the Lateral Branches TO THE Aortic Arches. RC, External carotid; h, lateral branch accompanying the hypoglossal nerve; IC, internal carotid; ICo, inter- costal; IM, internal mammary; 5, sub- clavian ; V, vertebral ; /to VIII, lateral cervical branches; i, 2, lateral thoracic branches. DEVELOPMENT OF THE ARTERIAL SYSTEM 247 iliacs, which seem from their size to be the continuations of the aorta rather than branches of it. The true continuation of the aorta is, however, the middle sacral artery, which represents in a degenerated form the caudal prolongation of the aorta of other mammals, and, like this, gives off lateral branches corresponding to the sacral segments. In addition to the segmental lateral branches arising from the aorta, visceral branches, which have their origin rather from the Fig. 153. — Diagram showing the Arrangement of the Segmental Branches arising from the aorta. A, Aorta; B, lateral somatic branch; C, lateral visceral branch; D, median visceral branch; E, peritoneum. ventral surface, also occur. In embryos of 5 mm. these branches are arranged in a segmental maimer in threes, a median unpaired vessel passing to the digestive tract and a pair of more lateral branches passing to the mesonephros (see p. 342) , corresponding to each of the paired branches passing to the body wall (Fig. 153). As development proceeds the great majority of these visceral branches disappear, certain of the lateral ones persisting, however, to form the renal, internal spermatic, and hypogastric arteries of the adult, while the unpaired branches are represented only 248 DEVELOPMENT OF THE ARTERIAL SYSTEM by the coeliac artery and the superior and inferior mesenteries. The superior mesenteric artery is the adult representative of the vitelHne artery of the embryo and arises from the aorta by two, three or more roots, which correspond to the fifth, fourth and higher thoracic segments. Later, all but the lowest of the roots disappear and the persisting one undergoes a downward migra- tion in accordance with the recession of the diaphragm and viscera (see p. 325) until in embryos of 17 mm. it hes opposite the first lumbar segment. Sim- ilarly the ccehac and inferior mesenteric arteries, which when first recognizable in em- bryos of 9 mm. correspond with the fourth and twelfth thoracic segments respect- ively, also undergo a second- ary downward migration, the coeliac artery in embryos of 17 mm. arising opposite the twelfth thoracic and the in- ferior mesenteric opposite the third lumbar segment. The umbiHcal arteries of the embryo seem at first to be the direct continuations of the dorsal aortse (Fig. 148), but as development proceeds they come to arise from the aorta opposite the third lumbar segment, where they are in fine with the lateral visceral segmental branches. They pass ventral to the Wolfl&an duct (see p. 341) and are continued out along with the allantois to the chorionic villi. Later this original stem is joined, not far from its origin, by what appears to be the lateral somatic branch of the fifth lumbar segment, whereupon the proximal part of the originalumbihcal vessel degenerates and the umbilical comes to arise from the somatic branch which is the common iliac artery Fig. 154.^ — Diagram Illustrating'the Development of the Umbilical Arteries. A, Aorta; CIl, common iliac; F.Il, ex- ternal iliac; G, gluteal; III, internal iliac; IP, internal pudic; IV, inferior vesical; Sc, sciatic; U, umbilical; £/', primary proximal portion of the umbilical ; ivd. Wolffian duct. DEVELOPMENT OF THE ARTERIAL SYSTEM 249 of adult anatomy (Fig. 154). Hence it is that this vessel in the adult gives origin both to branches such as the external ihac, the gluteal, the sciatic and the internal pudendal, which are distrib- uted to the body walls or their derivatives, and to others, such as the vesical, inferior haemorrhoidal and uterine, which are dis- tributed to the pelvic viscera. At birth the portions of the um- bilical arteries beyond the umbilicus are severed when the umbilical cord is cut, and their intraembryonic portions, which have been called the hypogastric arteries, quickly undergo a reduction in size. Their proximal portions remai n functional as the superor vesic al art e ri e s, carrying blood to the urinary bladder, but the portions which intervene b etween the bladder and thp umbilicus bec ome r educed to soUd cords, forminp^ the obliterated hypogastric art eries of a dult anatomy. In its general plan, accordingly, the arterial system may be regarded as consisting of a pair of longitudinal vessels which fuse together throughout the greater portion of their length to form the dorsal aorta, from which there arise segmentally arranged lateral somatic branches and ventral and lateral visceral branches. With the exception of the aortic trunks (together with their an- terior continuations, the internal carotids) and the external caro- tids, no longitudinal arteries exist primarily. In the adult, however, several longitudinal vessels, such as the vertebrals, internal mammary, and epigastric arteries, exist. The formation of these secondary longitudinal trunks is the result of a develop- ment between adjacent vessels of anastomoses, which become larger and more important blood-channels than the original vessels . At an early stage each of the lateral branches of the dorsal aorta gives off a twig which passes forward to anastomose with a back- wardly directed twig from the next anterior lateral branch; so as to form a longitudinal chain of anastomoses along each side of the neck. In the earliest stage at present known the chain starts from the lateral branch corresponding to the first cervical (suboccipital) segment and extends forward into the skull through the foramen magnum, terminating by anastomosing with the internal carotid. To this original chain other hnks are added from each of the sue- 2 so DEVELOPMENT OF THE ARTERIAL SYSTEM ceeding cervical lateral branches as far back as the seventh (Figs. 152 and 155). But in the meantime the recession of the heart toward the thorax has begun, with the result that the common carotid stems are elongated and the aortic arches are apparently VCK Fig. 155. — The Development of the Vertebral Artery in a Rabbit Embryo OF Twelve Days. IIIA.B to VIA.B, Branchial arch vessels; Ap, pulmonary artery. A.v.c.b and A.v.cv, cephalic and cervical portions of the vertebral artery; A.s, subclavian; C.d and C.v internal and external carotid; ISp.G, spinal ganglion. — (Hochstetter.) shortened so that the subclavian arises on the left side almost opposite the point where the aorta was joined by the sixth bran- chial vessel. As this apparent shortening proceeds, the various lateral branches which give rise to the chain of anastomoses, with the exception of the seventh, disappear in their proximal por- DEVELOPMENT OF THE ARTERIAL SYSTEM 25 1 tions and the chain becomes an independent stem, the vertebral artery, arising from the seventh lateral branch, which is the sub- clavian. The recession of the heart is continued until it Hes below the level of the upper intercostal arteries, and the upper two of these, together with the last cervical branch on each side, lose their con- nection with the dorsal aorta, and, sending off anteriorly and pos- teriorly anastomosing twigs, develop a short longitudinal stem, the costo-cervical trunk, which opens into the subclavian. Fig. 156- — Embryo of 13 mm. showing the Mode of Development of the In- ternal Mammary and Deep Epigastric Arteries. — {Mall.) The intercostals and their abdominal representatives, the lumbars and iHacs, also give rise to longitudinal anastomosing twigs near their ventral ends (Fig. 156), and these increasing in size give rise to the internal mammary and inferior epigastric arteries, which together form continuous stems extending from the subclavians to the external iliacs in the ventral abdominal walls. The superficial epigastrics and other secondary longitudi- nal vessels are formed in a similar manner. 2 52 DEVELOPMENT OF ARTERIES OF LIMBS The Development of the Arteries of the Limbs. — The earliest stages in the development of the limb arteries are unknown in man, but it has been found that in the mouse the primary supply of the anterior limb bud is from five branches arising from the sides of the aorta. These anastomose to form a plexus from which later a single stem, the subclavian artery, is elaborated, occupying the position of the seventh cervical segmental vessel, the remaining branches of the plexus having disappeared. The common iliac artery similarly represents the fifth lumbar segmental artery, but whether or not it also is elaborated from a plexus is as yet unknown. The later history of the limb arteries is also but imperfectly known and one must rely largely upon the facts of comparative anatomy and on the anomalies that occur in the adult for indica- tions of what the development is likely to be. The comparative evidence indicates the existence of several stages in the develop- ment of the Hmb vessels, and so far as embryological observations go they jconfirm the conclusions drawn from this source, although the various stages show apparently a great amount of overlapping owing to a concentration of the developmental stages. In the simplest arrangement the subclavian is continued as a single trunk along the axis of the limb as far as the carpus, where it divides into digital branches for the fingers. In its course through the fore- arm it lies in the interval between the radius and ulna, resting on the interosseous membrane, and in this part of its course it may be termed the arteria interossea. In the second stage a new artery accompanying the median nerve appears, arising from the main stem or brachial artery a Uttle below the elbow-joint. This may be termed the arteria mediana, and as it develops the arteria inter- ossea gradually diminishes in size, becoming finally the small volar interosseous artery of the adult (Fig. 157), and the median, uniting with its lower end, takes from it the digital branches and becomes the principal stem of the forearm. A third stage is then ushered in by the appearance of a branch from the brachial which forms the arteria ulnaris, and this, passing down the ulnar side of the forearm, unites at the wrist with the DEVELOPMENT OF ARTERIES OF LIMBS 253 median to form a superficial palmar arch from which the digital branches arise. A fourth stage is marked by the diminution of the median artery until it finally appears to be a small branch of the interosseous, and at the same time there develops from the bra- chial, at about the middle of the upper arm, what is known as the Fig. 157. — Diagrams showing an Early and a late Stage in the Development OF THE Arteries of the Arm. b. Brachial; i, interosseous; m, median; r, radial; rs, superficial radial; », ulnar. arteria radialis superficialis (Fig. 157, rs). This extends down the radial side of the forearm, following the course of the radial nerve, and at the wrist passes upon the dorsal surface of the hand to form the dorsal digital arteries of the thumb and index finger. At first this artery takes no part in the formation of the palmar arches, but later it gives rise to the superficial volar branch, which usually unites with the superficial arch, while from its dorsal portion a 254 DEVELOPMENT OF ARTERIES OF LIMBS perforating branch develops which passes between the first and second metacarpal bones and unites with a deep branch of the ulnar to form the deep arch. The fifth or adult stage is reached by the development from the brachial below the elbow of branch (Fig. 157, r) which passes downward and outward to unite with the superficial radial, whereupon the upper portion of that artery degenerates until it is represented only by a branch to the biceps ■*iriKpp Fig. 158. — Diagram illustrating the Development of the Artehies of the Leg. For the sake of Simplicity the Femoral Rete is Omitted. (After Senior) . ci. Inferior; cm, middle; cs, superior communicating branch; dp, dorsal plexus; /, femoral; g», inferior gluteal; /, interosseous; P.popliteus muscle; pc. perforating erural; pe, peroneal; pf, profunda femoris; po, popliteal; pp, plantar plexus; ps, superficial peroneal; pi, peforating tarsal; s, sciatic; ta. anterior tibial; tp, posterior tibial. muscle (Schwalbe), while the lower portion persists as the adult radial. The various anomalies seen in the arteries of the forearm are as a rule, due to the more or less complete persistence of one or other of the DEVELOPMENT OF ARTERIES OF LIMBS 255 stages described above, what is described, for instance, as the high branching of the brachial being the persistence of the superficial radial. In the leg there is a noticeable difference in the arrangement of the arteries from what occurs in the arm, in that the principal artery of the thigh, the femoral, does not accompany the principal nerve, the sciatic. This condition and the adult arrangement of the crural vessels have been found to be the result of a number of somewhat complicated changes (Senior), the more important of which are diagrammatically represented in Fig. 158. In the simplest stage, which is to be seen in embryos of 8.0-10.0 mm., a single artery extends down the back of the leg, passing anterior to the popliteus muscle and thence being continued down the crus on the interosseous membrane, to terminate in a plantar network, a branch (Fig. 158 ^, pt) passing through the tarsus to join a dorsal network. The upper part of this artery may be termed the sciatic, while its crural portion may be spoken of as the interrosseous. The femoral at this stage is represented by a network of vessels,, the femoral rete, which extends throughout the entire length of the thigh and with which the sciatic communicates by a branch passing between the adductor magnus and the femur (Fig. 158, B, Cs). In a later stage the superficial femoral and the profunda femoris differentiate from the femoral rete, the former being continuous with the branch of the sciatic that passes through the adductor magnus. From the sciatic a branch {po), which becomes the popliteal artey of the adult, passes down over the posterior surface of the popliteus, immediately below that muscle sending a branch {cni) to communicate with the interosseous, and divides a little lower down to form two vessels, one of which represents the posterior tibial (<^), while the other may be termed the superficial peroneal (ps). From this last a communicating branch (ci), extends downwards to join the lower part of the interosseous, from whose upper part a branch (pc) passes forward through the interosseous membrane and thence down the crus as the anterior tibial (td) to join the dorsal network. The plantar network is now connected with the interosseous, the superficial 256 DEVELOPMENT OF THE VENOUS SYSTEM peroneal and the posterior tibial, but the perforating tarsal branch which united it with the dorsal network has disappeared. This represents a condition from which the adult arrangement is formed by the disappearance of certain vessels (Fig. 158, C). Almost the whole of the sciatic vanishes, its uppermost portion persisting, however, to form the inferior gluteal (gi) and the branch of that vessel which accompanies the sciatic nerve, while a small portion of it, just where it joined the perforating crural branch, is retained to form the medial articular artery of the knee. The upper part of the interosseous also disappears, its lower part persisting as a portion of the adult peroneal (j>e), the upper part of which is formed by what was the communicating branch (ci) between the interosseous and the superficial peroneal, this latter artery vanishing. The terminal lateral calcaneal portion of the peroneal is a new formation and a perforating branch from the interosseous passes forward, through the lower part of the inter- osseous membrane, to join the anterior tibial. The dorsalis pedis and its branches are differentiated from the original dorsal network, while the plantar arteries are similarly derived from the plantar network. The Development of the Venous System. — The earliest veins to develop are those which accompany the first-formed ar'^eries, the umbiUcals, but it will be more convenient to consider first the veins which carry the blood from the body of the embryo back to the heart. These make their appearance, while the heart is still in the pharyngeal region, as two pairs of longitudinal trunks, the anterior and posterior cardinal veins, into which lateral branches, arranged more or less segmentally, open. The anterior cardinals appear somewhat earlier than the posterior and form the internal jugular veins of adult anatomy. In the head each vein passes along the side of the brain as the vena capitis prima, passing medial to the root of the trigeminus but lateral to the origins of the more posterior cranial nerves and receiving afferents from three plexuses which extend dorsally over the walls of the brain in the substance of the dura mater (Fig. 159 and 160, A). In embryos of about 20 mm. the anterior and middle plexuses have united (Fig. 160, C) DEVELOPMENT OF THE 't^'ENOTTS SYSTEM 2S7 and have developed a new pathway for their discharge, which passes backwards dorsal to the ear capsule to join the posterior plexus, through which it reaches the jugular foramen. At the same time the posterior pottion of the vena capitis prima dis- appears (Fig. 1 60, B and C), that portion of it, however, which passes medial to the trigeminus root persisting, since it receives Fig. 159. — Reconstruction of the Head of a Human Fmbryo of 9 mm. showing THE Cerebral Veins. acv. Anterior cerebral vein; au, auditory vesicle; cs, cavernous sinus; fa, facial nerve; mcv, middle cerebral vein; pcv, posterior cerebral vein; ir, trigeminal nerve; vcv, lateral cerebral vein. — (Mall.) from in front the opthalmic vein which has developed from the more anterior portions of the anterior plexus. This persisting portion of the vena capitis prima becomes the cavernous sinus of the adult and now drains into the trunk that passes dorsal to the ear capsule, by a vessel which represents the superior petrosal sinus of the adult. Later the superior sagittal sinus is differ- entiated from the dorsal portions of the anterior plexuses (Fig. 2S8 DEVELOPMENT O? THE VENOUS SYSTEM PLEXUS MEDIAU9 PLEXUS MEOIA1.I5 PLEXUS ANT PLEXUS CAGITTALIS /\' BIN. RECTUS S)N. SAGITTAUS SUP.^ PLEXUS ANT S N. TRANSVERSU^ E F Fig. i6o.— Six Stages in the Development of the Sinuses of thf Hitoa Mater. (Slreeter). ^^ DEVELOPMENT OP 'THE VENOUS SYSTEM 259 160 D), while the straight and inferior sagittal sinuses are elabor- ated from those portions of the plexuses which extend down be- tween the two cerebral hemispheres in the falx cerebri; and since the superior sagittal and straight sinuses open into the trunk which passes dorsal to the ear capsule, it is now clear that this trunk represents the transverse sinus of adult anatomy. The essential features of the adult arrangement are now completed by the formation of the inferior petrosal sinus (Fig. 160 D), this being practically a reconstitution of the posterior portion of the original vena capitis prima, and the various parts of the cerebral system of veins are brought into their adult relations by the straightening out of the nape bend and by the continued growth of the cerebral hemispheres. (Fig. 160, E and F). Passing backward from the jugular foramen th e internal iu gu- lar ve ins unite with the posterior cardinals to form on each side a common trunk, the ductus Cuvier i, which passing transversely to- ward the median line, opens into the side of the sinus venosus. So long as the heart retains its original position in the pharyngeal region the jugular is a short trunk receiving lateral veins only from the uppermost segments of the neck and from the occipital seg- ments, the remaining segmental veins opening into the inferior cardinals. As the heart recedes, however, the jugulars become more and more elongated and the cervical lateral veins shift their communication from the cardinals to the jugulars, until, when the subclavians have thus shifted, the jugulars become much larger than the cardinals. When tlip sinus vpnnsiif^ k ahgnrhpH intr. th^' wal l of the right auricl e, the course of the left Cuvierian duct be- comes a little longer than that of the right, and from the left jugu- lar, at the point where it is joined by the left subclavian, a branch arises which extends obliquely across to join the right jugular, forming the left innominate vein. When this is established, the connection between the left jugular and Cuvierian duct is dis- solved, the blood from the left side of the head and neck and from the left subclavian vein passing over to empty into the right jugular, whose lower end, together with the right Cuvierian duct, thus be- comes the superior vena cava. The left Cuvierian duct persists. 26o DEVELOPMENT OF THE VENOUS SYSTEM forming with the left horn of the sinus venosus the coronary sinus (Fig. i6i). The external jugular vein develops somewhat later than the internal. The facial vein, which primarily forms the principal affluent of this stem, passes at first into the skuU along with the fifth nerve and communicates with the internal jugular system, but later this original communication is broken and the facial vein, uniting with other superficial veins, passes over the jaw and ex- tends down the neck as the external jugular. Later still the facial Fig. i6i. — Diagrams showing the Development of the Superior Vena Cava. a, Azygos vein; cs, coronary sinus; ej, external jugular; h, hepatic vein, ij, internal jugular; inr and inl, right and left innominate veins; s, subclavian; vci and vcs, in- ferior and superior venae cavse. anastomoses with the ophthalmic at the inner angle of the eye and also makes connections with the internal jugular just after it has crossed the jaw, and so the adult condition is acquired. It is interesting to note that in many of the lower mammals the external jugular becomes of much greater importance than the internal the latter in some forms, indeed, eventually disappearing and the blood from the interior of the skull emptying by means of anastomoses which have developed into the external jugular system. In man the primi- tive condition is retained, but indications of a transference of the intracranial blood to the external jugular are seen in the emissary veins. The posterior cardinal veins, or, as they may more simply be termed, the cardinal s, extend backward from their union with the DEVELOPMENT OF THE VENOUS SYSTEM 261 jugulars along the sides of the vertebral column, receiving veins from the mesentery and also from the various lateral segmental veins of the neck and trunk regions, with the exception of that of the first cervical segment which opens into the jugular. Later, however, as already described (p. 259), the cervical veins shift to the jugulars, as do also the first and second thoracic (intercostal) veins, but the remaining intercostals, together with the lumbars and sacrals, continue to open into the cardinals. In addition, the cardinals receive in early stages the veins from the primitive kid- neys (mesonephros), which are exceptionally large in the human embryo, but as they become replaced later on by the permanent kidneys (metanephros) their afferent veins undergo a reduction in number and size, and this, together with the shifting of the upper lateral veins, produces a marked diminution in the size of the car- dinals. The changes by which they acquire their final arrange- ment are, however, so intimately associated with the development of the inferior vena cava that their description may be conven- iently postponed until the history of the vitelline and umbilical veins has been presented. The vitelline veins are two in number, a right and a left, and pass in along the yolk-stalk until they reach the embryonic intestine, along the sides of which they pass forward to unite with the corre- sponding umbilical veins. These are represented in the belly- stalk by a single venous trunk which, when it reaches the body of the embryo, divides into two stems which pass forward, one on each side of the umbilicus, and thence on each side of the median line of the ventral abdominal wall, to form with the corresponding vitelline veins common trunks which open into the ductus Cuvieri. As the liver develops it comes into intimate relation with the vitel- line veins, which receive numerous branches from its substance and, indeed, seem to break up into a network (Fig. 162, A) tra- versing the liver substance and uniting again to form two stems which represent the original continuations of the vitellines. From the point where the common trunk formed by the right vitel- line and umbiUcal veins opens into the Cuverian duct a new vein develops, passing downward and to the left to unite with the left 262 DEVELOPMENT OF THE VENOUS SYSTEM vitelline; this s the ductus venosus (Fig. 162, B, D.V.A.). In the meantime three cross-connections have developed between the two vitelline veins, two of which pass ventral and the other dorsal to the intestine, so that the latter is surrounded by two venous loops (Fig. 163, 4), and a; connection is developed between each umbilical vein and the corresponding vitelline (Fig. 162, B), that of the left side being the larger and uniting with the vitelline just where it is joined by the ductus venosus, so as to seem to be the continua- tion of this vessel (Fig. 162, C). When these connections are MC, ID.C yru.j: Vo.rn.s MC. MKi id/ru,, Vo.m.s J).c. 3.VA. KJ¥A. vas Fig. 162. — Diagrams Illustrating the Transformations of the Vitelline AND Umbilical Veins. B.S, Ductus Cuvieri; V.V.A, ductus venosus; V.o.m.i and V.o.m.s, right and left vitelline veins; V.u.d and V.u.s, right and left umbilical veins. — {Hochstetter.) complete, the upper portions of the umbilical veins degenerate (Fig. 163), and now the right side of the lower of the two vitelline loops which surround the intestine disappears, as does also that portion of the left side of the upper loop which intervenes between the middle cross-connection and the ductus venosus, and so there is formed from the vitelline veins the vena porta. While these changes have been progressing the right umbilical vein, originally the larger of the two (Fig. 162, A and B, V.u.d.), has become very much reduced in size and, losing its connection with the left vein at the umbilicus, forms a vein of the ventral ab- DEVELOPMENT OF THE VENOUS SYSTEM 263 dominal wall in which the blood now flows from above downward. The left umbilical now forms the only route for the return of blood from the placenta, and appears to be the direct continuation of the ductus venosus (Fig. 163, C), into which open the hepatic veins, re- turning the blood distributed by the portal vein to the substance of the liver. Returning now to the posterior cardinal veins, it has been found that in the rabbit the branches which come to them from the mesentery anastomose longitudinally to form a vessel lying parallel Fig. 163. — A, the Venous Trunks of an Embryo of s mm. seen from the Ventral Surface; B, Diagram Illustrating the Transformation to the Adult Con 3 tion. Vcd and Vcs, Right and left superior venae cava; Vj, jugular vein; V.om, vitelline vein; Vp, vena portae; Vu, umbilical vein (lower part); Vu', umbilical vein (upper part) ; Vud and Vus, right and left umbilical veins (lower parts). — {His.) and slightly ventral to each cardinal. These may be termed the subcardinal veins (Lewis), and in their earliest condition they open at either end into the corresponding cardinal, with which they are also united by numerous cross-branches. Later, in rabbits of 8.8 mm., these cross-branches begin to disappear and give place to a large cross-branch situated immediately below the origin of the superior mesenteric artery, and at the same point a cross branch between the two subcardinals also develops. The portion of the 264 DEVELOPMENT OF THE VENOUS SYSTEM right subcardinal which is anterior to the cross-connection now rapidly enlarges and unites with the ductus venosus about where the hepatic veins open into that vessel (Fig. 164 A), and the por- tion of each posterior cardinal immediately above the entrance of the renal veins degenerates, so that all the blood received by the posterior portions of the cardinals is returned to the heart by way of the right subcardinal, its cross-connections, and the upper part of the ductus venosus. Pig. 164. — Diagrams Illustrating the Development of the Inferior Vena Cava. The cardinal veins and ductus venosus are black, the subcardinal system blue, and the supracardinal yellow, cs, coronary sinus; dv, ductus venosus; il, iliac vein; r, renal; s, internal spermatic; sd, subclavian; sr, suprarenal; va, a,zygos;vka, hemi- azygos; vi, innominate; vj, internal jugular. When this is accomplished the lower portions of the subcardi- nals disappear, while the portions above the large cross-connec- tion persist, greatly diminished in size, as the suprarenal veins (Fig. 164, B). In the early stages the veins which drain the posterior abdomi- nal walls empty into the posterior cardinals, and later they form, in DEVELOPMENT OF THE VENOUS SYSTEM 265 the region of the kidney on each side, a longitudinal anastomosis which opens at either extremity into the posterior cardinal. The ureter thus becomes surrounded by a venous ring, the dorsal limb of which is formed by the new longitudinal anastomosis, which has been termed the supracardinal vein (McClure and Huntington) while the ventral limb is formed by a portion of the posterior cardinal (Fig. 164, B). Still later the ventral limb of the loop disappears and the dorsal supracardinal limb replaces a portion of the more primitive posterior cardinal. An anastomosis now develops between the right and left cardinals at the point where the Uiac veins open into them (Fig. 163, 5), and the portion of the left cardinal which intervenes between this anastomosis and the entrance of the internal spermatic vein disappears, the remainder of it, as far forward as the renal vein, persisting as the upper part of the left internal spermatic vein, which thus comes to open into the renal vein instead of into the vena cava as does the corre- sponding vein of the right side of the body (Fig. 164, C,s). The renal veins originally open into the cardinals at the point where these are joined by the large cross-connection, and when the lower part of the left cardinal disappears, this cross-connection forms the proximal part of the left renal vein, which consequently receives the left suprarenal (Fig. 164, C). The observations upon which the above description is based have been made chiefly upon the rabbit and pig, but it seems pro- bable from the partial observations that have been made that sim- lar changes occur also in the human embryo. It will be noted from what has been said that the inferior vena cava is a composite vessel, consisting of at least four elements: (i) the proximal part of the ductus venosus; (2) the anterior part of the right sub- cardinal; (3) the right supracardinal; and (4) the posterior part of the right cardinal. The complicated development of the inferior vena cava naturally gives rise to numerous anomalies of the vein due to inhibitions of its development. These anomalies affect especially the post-renal portion a persistence of both cardinals (interpreting the conditions in the terms of what occurs in the rabbit) giving rise to a double post-renal 266 DEVELOPMENT OF THE VENOUS SYSTEM cava, or a persistence of the left cardinal and the disappearance of the right to a vena cava situated on the left side of the vertebral column and crossing to the right by way of the left renal vein. So, too the occurrence of accessory renal veins passing dorsal to the ureter is ex- plicable on the supposition that they represent portions of the supra- cardinal system of veins. It has already been noted that the portions of the posterior cardinals immediately anterior to the entrance of the renal veins disappear. The thoracic portion of the right vein persists, how- ever, and becomes the vena azygos of the adult, while the upper portion of the left vein sends a cross-branch over to unite with the azygos and then separates from the coronary sinus to form the vena hemiazygos. At least this is what is described as occur- ring in the rabbit, ^n the cat, however, only the very uppermost portion of the right posterior cardinal persists and the greater portion of the azygos and perhaps the entire hemizaygos vein is formed from the prerenal portions of the supracardinal veins, the right one joining on to the small persisting upper portion of the right posterior cardinal, while the cross-connection between the hemiazygos and azygos represents one of the originally numerous cross-connections between the supracardinals. The ascending lumbar veins, frequently described as the commence- ments of the azygos veins, are in reality secondary formations de- veloped by the anastomoses of anteriorly and posteriorly directed branches of the lumbar veins. The Development of the Veins of the Limbs. — The development of the limb veins of the human embryos requires further investiga- tion, but from a comparison of what is known with what has been observed in rabbit embryos it may be presumed that the changes which take place are somewhat as follows: In the anterior ex- tremity the blood brought to the limb is collected by a vein which , passes distally along the radial border of the Umb bud, around its distal border, and proximally along its ulnar border to open into the anterior cardinal vein; this is the primary ulnar vein. Later a second vein grows out from the external jugular along the radial border of the limb, representing the cephalic vein of the adult, and on its appearance the digital veins, which were formed from the THE FETAL CIRCULATION 267 primary ulnar vein, becomes connected with it, and the distal portion of the primary ulnar vein disappears. Its proximal por- tion persists, however, to form the basilic vein, from which the brachial vein and its continuation, the ulnar vein, are developed, while the radial vein develops as an outgrowth from the cephalic, which at an early stage secures an opening into the axillary vein, its original communication with the external jugular forming the jugulo-cephaHc vein. In the lower limb a primary fibular vein, exactly comparable to the primary ulnar of the arm, surrounds the distal border of the limb-bud and passes up its fibular border to open with the poste- rior cardinal vein. The further development in the lower limb dif- fers considerably, however, from that of the upper limb. From the primary fibular vein an anterior tibial vein grows out, which re- ceives the digital branches from the toes, and from the posterior cardinal, anterior to the point where the primary fibular opens into it, a vein grows down the tibial side of the leg, forming the long saphenous vein. From this the femoral vein is formed and from it the posterior tibial vein is continued down the leg. An anastomo- sis is formed between the femoral and the primary fibular veins at the level of the knee and the proximal portion of the latter vein then becomes greatly reduced, while its distal portion possibly persists as the small saphenous vein (Hochstetter). The Pulmonary Veins. — The development of the pulmonary veins has already been described in connection with the develop- ment of the heart (see p. 235). The Fetal Circulation. — During fetal life while the placenta is the sole organ in which occur the changes in the blood on which the nutrition of the embryo depends, the course of the blood is neces- sarily somewhat different from what obtains in the child after birth. Taking the placenta as the starting-point, the blood passes along the umbiHcal vein to enter the body of the fetus at the umbili- cus, whence it passes forward in the free edge of the ventral mesen- tery (see p. 324) until it reaches the liver. Here, owing to the anastomoses between the umbilical and vitelline veins, a portion of the blood traverses the substance of the liver to open by the hepat- 268 THE FETAL CIRCULATION ic veins into the inferior vena cava, while the remainder passes on through the ductus venosus to the cava, the united streams open- ing into the right atrium. This blood, whose purity is only slightly reduced by mixture with the blood returning from the in- FiG. 165. — The Fetal C^RCULAIIo^^. eo, Aorta; a.pu., pulmonary artery; au, umbilical artery; da, ductus arteriosus; dv, ductus venosus; int, intestine; vci and vsc, inferior and superior vena cava* vh, hepatic vein; vp, vena portae; v.pu, pulmonary vein; vu, umbilical vein. — (From Kollmann.) ferior vena cava, is prevented from passing into the right ventricle by the Eustachian valve, which directs it to the foramen ovale, and through this it passes into the left atrium, thence to the left ventricle, and so out by the systemic aorta. THE FETAL CIRCULATION 269 The blood which has been sent to the head, neck, and upper extremities is returned by the superior vena cava also into the right atrium, but this descending stream opens into the atrium to right of the annulus of Vieussens (see Fig. 143) and passes directly to the right ventricle without mingHng to any great extent with the blood returning by way of the inferior cava. From the right ven- tricle this blood passes out by the pulmonary artery; but the lungs at this period are collapsed and in no condition to receive any great amount of blood, and so the stream passes by way of the ductus arteriosus into the systemic aorta, meeting there the placental blood just below the point where the left subclavian artery is given off. From this point onward the aorta contains only mixed blood, and this is distributed to the walls of the thorax and ab- domen and to the lungs and abdominal viscera, the greater part of it, however, passing off in the hypogastric arteries and so out again to the placenta. This is the generally accepted account of the fetal circulation and it is based upon the idea that the foramen ovale is practically a con- nection between the inferior vena cava and the left atrium. If it be correct the right ventricle receives only the blood returning to the heart by the vena cava superior, while the left receives all that returns by the inferior vena cava together with what returns by the pulmonary veins. One would, therefore, expect that the capacity and pressure of the right ventricle would in the fetus be less than those of the left. Pohlman, who has recently investigated the question in embryo pigs, finds, on the contrary, that the capacities and pressures of the two ventricles are equal and maintains that the foramen ovale is actually a connection between the two atria. That is to say, he holds that there is an actual mingling of the blood from the two venae cavae in the right atrium, whence the mixed blood passes to the right ventricle, a certain amount of it, however, passing through the foramen ovale and so to the left ventricle to equalize the deficiency that would otherwise exist in that chamber owing to the small amount of blood returning by the pulmonary veins. According to this view there would be no difference in the quality of the blood distributed to different portions of the body, such as is provided for by the current theory; all the blood leaving the heart would be mixed blood and in favor of this view is the fact that starch granules injected into either the superior or the inferior vena cava in living pig embryos were in all cases re- covered from both sides of the heart. , 270 DEVELOPMENT OF THE LYMPHATIC SYSTEM At birth the lungs at once assume their functions, and on the cutting of the umbilical cord all communication with the placenta ceases. Shortly after birth the foramen ovale closes more or less perfectly, and the ductus arteriosus diminishes in size as the pul- monary arteries increase and becomes eventually converted into a fibrous cord. The hypogastric arteries diminish greatly, and after they have passed the bladder are also reduced to fibrous cords, a fate likewise shared by the umbilical vein, which becomes con- verted into the round ligament of the liver. The Development of the Lymphatic System. — The lymphatic system is associated with the blood-vascular system both in its adult condition and in its development. Indeed, at one stage it is virtually a part of the blood-vascular system, being represented by capillary networks hardly distinguishable from adjacent blood capillaries, containing blood like these and being connected with neighboring venous trunks. These networks are developed in definite regions of the body, one being formed in relation with the proximal portion of each anterior cardinal (internal jugular) vein, another pair appearing along the hues of the iliac veins, while another, unpaired, develops in the root of the mesentery along the line of the median vein draining the mesonephros (see p. 342) . In later stages the vessels forming these networks dilate and unite together to form sac-Hke structures, termed lymph sacs, which are accordingly five in number, i.e., two jugular (Fig. 166, ALH), two iliac (Fig. 166, PLE) and one retroperitoneal (Fig. 167 Isr). At first these lymph sacs still contain blood and are con- nected with the neighboring venous trunks, but later they evacuate their blood contents and separate from the veins, forming inde- pendent sacs lined by endothelium. In relation with these as centers the remaining portions of the lymphatic system, the tho- racic duct and the peripheral vessels, develop, the sacs themselves eventually becoming transformed into groups of lymphatic nodes the jugular ones, however, re-establishing connections between the lymphatic and venous systems by uniting with the junctions of the jugular and subclavian veins. With regard to the development of the thoracic duct and per- DEVELOPMENT OF THE LYMPHATIC SYSTEM 271 ipheral vessels, as well as with regard to the first formation of the primary networks from which the lymph sacs develop, two dis- cordant views exist. According to one (Sabin, Lewis) the net- works are formed by the union of a number of outgrowths from Fig. 166. — Diagrams showing the Arrangement of the Lymphatic Vessels in Pig Embryos of (A) 20 mm. and {B) 40 mm. ACV, Jugular vein; ADR, suprarenal body; ALH, jugular lymph sac; Ao, aorta; Arm D, deep lymphatics to the arm; D, diaphragm; Du, branches to duodenum; FV, femoral vein; H, branches to heart; K, kidney; Leg D, deep lymphatics to leg; Lu, branches to lung; MP, branches to mesenteric plexus; CE, branch to oesophagus; PCV, cardinal vein; PLH, posterior lymph sac; RC, cisterna chyli; RLD, right lymphatic duct; ScV, subclavian vein; SV, sciatic vein; St, branches to stomach; TD, thoracic duct; WB, Wolffian body. — (Sabin.) the veins and the peripheral vessels are formed by a process of budding from the lymph sacs, outgrowths of the endothelium of 272 DEVELOPMENT OF THE LYMPHATIC SYSTEM these radiating into the surrounding mesenchyme. From the jugular sacs are formed the vessels which drain the upper half of each side of the body and the arms, from the iliac sacs those drain- ing the walls of the lower half of each side of the body, the perma- nent kidneys and the legs, and from the retroperitoneal sac the vessels draining the remaining abdominal and pelvic viscera. The Fig. i67.^Diagram of the Posterior Portion of the Body of a Human Embryo of ^3 mm., showing the Relations of the Retroperitoneal Lymph Sac and the Cisterna Chyli to the Veins. Am, Superior mesenteric artery; Ao, aorta; Cc, cisterna chyli; ^jc, retroperitoneal lymph sac; 5, suprarenal body; Va, vena azygos; Vci, vena cava inferior; vh, first lumbar vertebra; vsi, first sacral vertebra. — {After Sabin.) thoracic duct is formed by the union of two originally distinct portions, one, a downward growth from the left jugular sac and the other a network formed from outgrowths from the retroperi- toneal sac. This network lies behind the aorta and gives rise to the cisterna chyU and the greater portion of the thoracic duct, the frequent duplication of this structure, especially in its lower por- tion, being thus readily understood from its mode of development. DEVELOPMENT OF THE LYMPHATIC SYSTEM 273 According to this view the endothelium lining the lymphatic vessels is derived directly from that lining the blood-vessels and the development of the peripheral lymphatics is by a centrifugal growth from the lymph sacs. According to the opposing view (Huntington, McClure) the lymphatics in their initial stage are independent of the blood-vessels, appearing as a number of inter- cellular clefts in the mesenchyme along the line of venous trunks. These clefts become lined by an endo- thelium, blood corpuscles from adjacent blood-islands make their way into them and gradually the clefts unite together to form a capillary network which makes connections with the neighboring vein. In this way are formed the pri- mary networks from which the lymph sacs develop, and the same process leads to the formation of the thoracic duct and the peripheral lymphatics, the duct, for example, arising by the union of a series of clefts in the mesenchyme along the Une of the left posterior cardinal vein, the canal so formed eventually uniting with the left jugular lymph sac. On this view the primary lymphatic net- works serve to convey to, the main venous trunks the blood which is being formed in isolated blood-islands through- out the mesenchyme, and it is only secondarily, on the cessation of the haematopoietic function of the mesenchyme, that they take on the lymphatic function. Their endothelium arises quite inde- pendently of that of the blood-vascular system and the mode of growth of the vessels is, in a sense, centripetal toward the lymph sacs. Lymph nodes have not been observed in human embryos until toward the end of the third month of development, • but they appear in pig embryos of 3 cm. Their unit of structure is a 18 Fig. 168. — Diagram of a Primary Lymph Node of an Embryo Pig of 8 cm. a. Artery; aid, afferent lymph duct; eld, efferent lymph duct; /, follicle. — {Sabin.) 274 DEVELOPMENT OF THE LYMPHATIC SYSTEM blood-vessel, breaking up at its termination into a leash of capil- laries, around which a condensation of lymphocytes occurs in the mesenchjone. A structure of this kind form6 what is termed a lymphoid follicle and may exist, even in this simple condition, in the adult. More frequently, however, there are associated with the follicle lymphatic vessels, or rather the follicle develops in a network of lymphatic vessels, which become an investment of the Fig. 169. — Developing H.emolymph Node. be, central blood-vessel; 6fe, blood-vessel at hilus; ps, peripheral blood sinus.- from Morris' Human Anatomy.) -(Sabin follicle and form with it a simple lymph node (Fig. 168). This condition is, however, in many cases but transitory, the artery branching and collections of lymphoid tissue forming around each of the branches, so that a series of follicles is formed, which, together with the surrounding lymphatic vessels, becomes enclosed by a connective- tissue capsule to form a compound lymph node. Later trabeculae of connective tissue extend from the capsule DEVELOPMENT OF THE SPLEEN 275 toward the center of the node, between the follicles, the lymphatic network gives rise to peripheral and central lymph sinuses, and the follicles, each with its arterial branch, constitute the peripheral nodules and the medullary cords, the portions of these immediately surrounding the leash of capillaries into which the artery dissolves, constituting the so-called germ centers in which multiplication of the l3Tnphocytes occurs. In various portions of the body, but especially along the root of the mesentery, what are teriped hamolymph nodes occur. In these the lymph sinus is replaced by a blood sinus, but with this ex- ception their structure resembles that of an ordinary lymph node, a simple one consisting of a follicle, composed of adenoid tissue with a central blood-vessel, and a peripheral blood sinus (Fig. 169). The Development of the Spleen.^ — Recent studies (Mall) have shown that the spleen may well be regarded as possessing a struc- ture comparable to that of the lymph nodes, the pulp being more or less distinctly divided by trabeculae into areas termed pulp cords, the axis of each of which is occupied by a twig of the splenic artery, while the Malpighian corpuscles may be regarded as lymph follicles. The spleen, therefore, seems to fall into the same category of or- gans as the lymph and haemolymph nodes, dififering from these chiefly in the absence of sinuses. It has generally been regarded as a development of the mesenchyme situated between the two layers of the mesogastrium. To this view, however, recent ob- servers have taken exception, holding that the ultimate origin of the organ is in part or entirely from the coelomic epithelium of the left layer of the mesogastrium. The first indication of the spleen has been observed in embryos of the fifth week as a slight elevation on the left (dorsal) surface of the mesogastrium, due to a local thickening and vascularization of the mesenchyme, accompanied by a thickening of the coelomic epitheHum which covers the ele- vation. The mesenchyme thickening presents no differences from the neighboring mesenchyme, but the epithelium is not distinctly separated from it over its entire surface, as it is elsewhere in the mesentery. In later stages, which have been observed in detail 276 DEVELOPMENT OF THE SPLEEN in pig and other amniote embryos, cells separate from the deeper layers of the epithelium (Fig. 170) and pass into the mesenchyme thickening, whose tissue soon assumes a different appearance from the surrounding mesenchyme by its cells being much crowded. This migration soon ceases, however, and in embryos of forty-two days the coelomic epithelium covering the thickening is reduced to a simple layer of cells. The later stages of development consist of an enlargement of the thickening and its gradual constriction from the surface of the ^^^!!9»' %%^(^ ~~^-':: PlG. 170. — Section through the Left Layer of the Mesogastrium of a Chick I Embryo of Ninety-three Hours, Showing the Origin of the Spleen, ep, Coelomic epithelium; ms, mesenchyme. — (Tonkoff.) mesogastrium, until it is finally united to it only by a narrow band through which the large splenic vessels gain access to the organ. The cells differentiate themselves into trabeculae and pulp cords special collections of lymphoid cells around the branches of the splenic artery forming the Malphigian corpuscles. It has already been pointed out (p. 227) that during embryonic life the spleen is an important hasmatopoietic organ, both red and white corpuscles undergoing active formation within its substance. The Malpighian corpuscles are collections of lymphocytes in which multipli- cation takes place, and while nothing is as yet known as to the fate of the cells which are contributed to the spleen from the coelomic epithelium, since they quickly come to resemble the mesenchyme cells with which they are associated, yet the growing number of observations indicating an epithelial origin for lymphocytes suggests the possibility that the cells in question may be responsible for the first leukocytes of the spleen. The Coccygeal or Luschka's Ganglion. — In embryos of about 15 cm. there is to be found on the ventral surface of the apex of the LITERATURE 277 coccyx a small oval group of polygonal cells, clearly separated from the surrounding tissue by a mesenchymal capsule. Later connective-tissue trabeculae make their way into the mass, which thus becomes divided into lobules, and, at the same time, a rich vascular supply, derived principally from branches of the middle sacral artery, penetrates the body, which thus assumes the adult condition in which it presents a general resemblance to a group of Ijonph follicles. It has generally been supposed that the coccygeal ganglion was in part derived from the sympathetic nervous system and belonged to the same group of organs as the suprarenal bodies. The most recent work on its development (Stoerk) tends, however, to dis- prove this view, and the ganglion seems accordingly to find its place among the lymphoid organs. LITERATURE W. A. Baetjer: 'On the Origin of the Mesenteric Sac and the Thoracic Duct in the Embryo Pig, ' Amer. Journ. Anat., 1, 1908. E. VAN Beneden and C. Julin: "Recherches sur la formation des annexes foetales chez les mammifdres," Archiv. de Biolog., v, 1884. A. C. Bern ays: " Entwicklungsgeschichte der Atrioventricularklappen,'' Morphol. Jahrbuch, 11, 1876. G. Born: "BeitrSge zur Entwicklungsgeschichte des Saugethierherzens," Archit fur mikrosk. Anat., xxxLU, 1889. J. L. Beemer: "On the Origin of the Pulmonary Arteries in Mammals," Anat Record, rn, 1909. I. Broman: "Ueber die Entwicklung, Wanderung und Variation der Bauchaorten- zweige bei den Wirbeltiere," Ergeb. Anat. und Entwick., xvi, r9o6, I. Broman: "Ueber die Entwicklimg und "Wanderung" der Zweige der aorta ab- dominalis beim Menschen," Anat. Hefte, xxxvi, 1908. E. E. Butterpield: "Ueber die ungranulierte Vorstufen der Myelocyten und ihre Bildung in Milz, Leber und Lymphdrlisen," Deutsch. Arch. f. klin. Med., xcii, 1908. E. R. Clark: "Observations on Living Growing Lymphatics in the Tail of the Frog Larva," Anat. Record, in, 1909. C. B. Coulter: "The Early Development of the Aortic Arches of the Cat, with Especial Reference to the Presence of a Fifth Arch," Anat. Record, ra, 1909. Vera Danchakoff: "Origin of the blood cells. Development of the haematopoi- etic organs and regeneration of blood cells from the standpoint of the monophy- letic school," Anat. Rec, x, 1916. D. M. Davis: "Studies on the chief veins in early pig embryos and the origin of the vena cava inferior," Amer. Journ. Anat.,x, 1910. 278 LITERATURE J. Disse: "Die Entstehung des Blutes und der ersten Gefasse im Huhnerei," Archiv fiir mikrosk. Anat., xvi, 1879. A. C. F. Eternod: "Premiers stades de la circulation sanguine dans I'oeuf et I'em- bryon humain," Anat. Anzeiger, xv, 1899. H. M. Evans: "On the Development of the Aortae, Cardinal and Umbilical Veins, and the other Blood-vessels of Vertebrate Embryos from Capillaries," Anat. Record, m, 1909. V. Federow: "Ueber die Entwicklung der Lungenvene," Anat.. Hefte, XL, 1910. W. Felix: "Zur Entwicklungsgeschichte der Rumpfarterien des menschlichen Embryo," Morphol. Jahrb., XLi, 1910. G. J. Heuer: "The Development of the Lymphatics in the Small Intestine of the Pig," Amer. Journ. Anat., ix, 1909. W. His: "AnatomiemenschlicherEmbryonen," Leipzig, 1880-1882. F. Hochstetter: "Ueber die ursprungliche Hauptschlagader der hinteren Glied- masse des Menschen und der Saugethiere, nebst Bemerkungen uber die Ent- wicklung der Endaste der Aorta abdominalis," Morphol. Jahrbuch, xvi, i8go. F. Hochstetter: "Ueber die Entwicklung der A. vertebralis beim Kaniuchen, nebst Bemerkungen iiber die Entstehung der Ansa Vieusseni," Morphol. Jahrbuch, XVI, 1890. F. Hochstetter: "Beitrage zur Entwicklungsgeschichte des Venensystems der Amnioten," Morphol. Jahrbuch, xx, 1893. W. H. Howell: "The Life-history of the Formed Elements of the Blood, Especially the Red Blood-corpuscles," Journ. of Morphol., iv, 1890. W. H. Howell: "Observations on the Occurrence, Structure, and Function of the Giant-cells of the Marrow," Journ. of Morph., iv, 1890. G. S. Huntington: "The Genetic Principles of the Development of the Systemic Lymphatic Vessels in the Mammalian Embryo," Anat. Record, iv, 1910. G. S. Huntington: "The Anatomy and Development of the Systemic Lymphatic Vessels of the Domestic Cat," Memoirs of Wistar Institute, i, 1912. G. S. Huntington: "The Development of the Mammalian Jugular Lymph Sac, Etc.," Amer. Journ. Anat., xvi, 1914. G. S. Huntington. The Morphology of the Pulmonary Artery in the Mammalia," Anat. Record, vii, 1919. G. S. Huntington and C. F. W. McClure: "Development of Post-cava and Tribu- taries in the Domestic Cat," Amer. Journ. Anat., vi, 1907. G. S. Huntington and C. F. W. McClure: "The Development of the Main Lymph Channels of the Cat in their Relations to the Venous System," Amer. Journ. Anat., VI, 1907. G. S. Huntington and C. F. W. McClure: "The Anatomy and Development of the Jugular Lymph Sacs in the Domestic Cat," Amer. Journ. Anat., x, 1910. H. E. Jordan: "A Microscopical Study of the Umbilical Vesicle of a 13 mm. Human Embryo, with Special Reference to the Entodermal Tubules and the Blood Islands," Anat. Anzeiger, xxxvii, 1910. O. F. Kampmeier: "The development of the thoracic duct in the pig," Amer. Journ. Anat., XIII, 1912. C. A. Kling: "Studien uber die Entwicklung der Lymphdrvisen beim Menschen," Archiv. fiir mikrosk. Anat., Lxin, 1904. LITERATURE 279 H. Lehmann : " On the Embryonic History of the Aortic Arche? in Mammals, " A nat. Ameiger, xxvi, 1905. F. T. Lewis : "The Development of the Vena Cava Inferior," Amer. Journ. of Anat., I, 1902. F. T. Lewis: "The Development of the Veins in the Limbs of Rabbit Embryos," Amer. Journ. Anat., v, 1906. F.T. Lewis: "The Development of the Lymphatic System in Rabbits," Amer. Journ. Anat., V, 1906. F. T. Lewis: "On the Cervical Veins and Lymphatics in Four Human Embryos," Amer. Journ. Anat., DC, 1909. F. T. Lewis: "The First Lymph Glands in Rabbit and Human Embryos," Anat. Record, in, 1909. W. A. Locy: " The Fifth and Sixth Aortic Arches in Chick Embryos, with Comments on the Condition of the same Vessels in other Vertebrates," Anat. Anzeiger XXK, igo6. F. P. Mall: "Development of the Internal Mammary and Deep Epigastric Arteries in Man," Johns Hopkins Hospital Bulletin, 1898. F.P. Mall: "On the Development of the Blood-vessels of the Brain in the Human Embryo," Amer. Journ. Anat., iv, 1905. F. P. Mall: "On the Development of the Human Heart," Amer. Journ. Anal., xm, igi2. A. Maximow: "Untersuchungen iiber Blut und Bindegewebe," Arch, jiir mikr. Anat., Lxxni, 1909; Lxxiv, 1909; lxxvi, igio. C.F.W. McClure: "The Development of the Thoracic and Right Lymphatic Ducts in the Domestic Cat (Felis Domestica)," Anat. Anzeiger, xxxn, 1908. C. F. W. McCluee: "The Extra-intimal Theory of the Development of the Mesen- teric Lymphatics in the Domestic Cat," Verhandl. Anat. Gesellsch., xxiv, 1910. C. F. W. McCluee: "The Development of the Lymphatic System in the Light of the More Recent Investigations in the Field of Vasculogenesis," Anat. Rec, IX, 1915. C, S. Minot: "On a Hitherto Unrecognized Form of Blood Circulation without Capillaries in the Organs of Vertebrata," Proc. Boston Soc. Nat. Hist., xxix, 1900. S. Mollier: "Die Blutbildung in der Embryonalen Leber des Menschen und der Saiigetiere," Arch.fiir mikrosk. Anat., Lxxrv, 1909. C. V. Morill: "On the Development of the Atrial Septum and the Valvular Apparatus in the Right Atrium of the Pig Embryo," Amer. Journ. Anat., xx, 1916. A. G. Pohlman: "The Course of the Blood through the Fetal Mammalian Heart," Anat. Record, n, 1908. F. Reagan: "The Fifth Aortic Arch of Mammalian Embryos," Amer. Journ. Anal., XII, 1912. F.P.Reagan: "Experimental Studies on the Origin of Vascular Endothelium and of Erythrocytes," Amer. Journ. Anat., xxi, 191 7. E. Retterer: "Sur la part que prend I'epithfilium k la formation de la bourse de Fabricius, des amygdales et des plaques de Peyer," Journ. de I' Anat. el de la Physiol., XXK, 1893. 28o LITERATURE R. Retzer: "Some Results of Recent Investigations on the Mammalian Heart,'' Anat. Record, ii, 1908. C. Rose: "Zur Entwicklungsgeschichte des Saugethierherzens,'' Morphol. Jahrbuch, XV, 1889. Florence R. Sabin: "On the Origin of the Lymphatic System from the Veins and the Development of the Lymph Hearts and Thoracic Duct in the Pig," Anter. Journ. of Anat., 1, 1902. Florence R. Sabin: "The Development of the Lymphatic Nodes in the Pig and their Relation to the Lymph Hearts," Amer. Journ. Anat., rv, 1905. Florence R. Sabin: "Further Evidence on the Origin of the Lymphatic Endothe- lium from the Endothelium of the Blood Vascular System," Anat. Record, 11, 1908. Florence R. Sabin: "On the Development of the Lymphatic System in Human Embryos with a Consideration of the Morphology of the System as a Whole," Amer. Journ. Anat., rx, 1909. Florence R. Sabin : " A Critical Study of the Evidence Presented in Several Recent Articles on the Development of the Lymphatic System," Anat. Record, v, 1911. Florence R. Sabin: "Der Ursprung und die Entwicklung des Lymphgef ass- systems," Ergb. Anat. u. Entw., xxi, 1913. Florence R. Sabin: "On the Fate of the Posterior Cardinal Veins, etc., in the Embryo Pig," Carnegie Inst. Pub. Contrib. to EmbryoL, III, 1915. Florence R. Sabin: "Preliminary Note on the Differentiation of Angioblasts and the Method by which they Produce Blood-vessels, Blood plasma and Red Blood-cells as Seen in the Living Chick," Anat. Rec, xin, 1917. F. Saxer: "Ueber die Entwicklung und der Ban normaler Lymphdriisen und die Entstehung der roten und weissen BlutkSrperchen," Anat. Hefte, vi, 1896. R. E. Scammon and E. H. Norris: "On the Time of the Post-natal Obliteration of the Fetal Blood-passages (Foramen Ovale, Ductus Arteriosus, Ductus Venosus), Anat. Rec. xv, 1918. H. Schridde: "Die Entstehung der ersten embryonalen Blutzellen des Menschen," Folia hcematol, iv, 1907. H. von W. Schtjlte: "Early Stages of Vasculogenesis in the Cat (Felis Domestics), with Especial Reference to the Mesenchymal Origin of Endothelium, Mem. Wistar Inst., No. 3, 1914. H. VON W. Schulte: "The Fusion of the Cardiac Anlages and the Formation of the Cardiac Loop in the Cat (Felis Domestica)," Amer. Journ. Anat.,xx, 1916. H. D. Senior: "The Development of the Arteries of the Human Lower Extremity, Amer. Journ. Anat , xxv, 1919. See also Anat. Record, xvii, 1920. H. D. Senior: "An Interpretation of the Recorded Arterial Anomalies of the Human Leg and Foot," Journ. Anat., lui, 1919. L. Stienon: "Sur la Fermature du Canal de Botal," Arch, de Biol., xxvii, 1912. C. R. Stockard: "The Origin of Blood and Vascular Endothelium in Embryos without a Circulation of the Blood and in the Normal Embryo," Amer. Journ. Anat., xvni, 1915. P. Stohr: "Ueber die Entwicklung der Darmlymphknotchen und iiber die Rilck- bildung von Darmdriisen." Archiv fiir mikrosk. Anat., li, 1898. LITERATURE 28 I O. Stoerk: "Ueber die Chromreaktion der Glandula coccygea und die Beziehung, dieser Driise zura Nervus sympathicus," Arch.fur mihroskop. Anal., Lxrx, 1906. G. L. Streeter: "The Development of the Venous Sinuses of the Dura Mater in the Human Embryo," Amer. Journ. Anat., xvin, 1915. G. L. Streeter: "The Developmental Alterations in the Vascular System of the Brain of the Human Embryo,'' Carnegie Inst. Puhl. 271, Contrib. to Embryo!. No. 24, 1919. O. VAN DER Stricht: "Nouvelles recherches sur la genfee des globules rouges et des globules blancs du sang," Archives de Biolog., xii, 1892. O. VAN DER Stricht: " De la premiere origine du sang et des capillaires sanguins dans I'aire vasculaire du Lapin," Comptes Rendus de la Soc. de Biolog. Paris, S6r. 10, It, 1895. J. Tandler: "Zur Entwicklungsgeschichte der Kopfarterien bei den Mammalia," Morphol. Jahrbuch, xxx, 1902. J. Tandler: "Zur Entwickelungsgeschichte der menschlichen Darmarterien," Anat. Befte, xxirr, 1903. J. Tandler: "Ueber die Varietaten der arteria coeliaca und deren Entwicklung," Anat. Hefte, xxv, 1904. J. Tandler: "Ueber die Entwicklung des fiinften Aortenbogens und der funften Schlundtasche beim Menschen," Anat. Hefte, xxxvm, 1909. W. ToNKorr: "Die Entwickelung der Milz bei den Amnioten," Arch, fiir mikrosk. Anal., LVi, 1900. Bertha de Vriese: " Recherches sur revolution des vaissaux sanguins des membres chez I'homme," Archiv de Biolog., xvni, 1902. F. Weidenreich: "Die roten Blutkorperchen," Ergb. Anat. und Entwick., xiii, 1903, XIV, 1904. F. Weidenreich: "Die Leucocyten und verwandte Zellformen," Ergeb. Anat. und Entwick., XVI, 1911. J. H. Wright: "The Histogenesis of the Blood Platelets,'' Journ. of Morph., xxi, 1910. CHAPTER X THE DEVELOPMENT OF THE DIGESTIVE TRACT AND GLANDS The greatest portion of the digestive tract is formed by the constriction off of the dorsal portion of the yolk-sac, as shown in Fig. 53, the result being the formation of a cylinder, closed at either end and composed of a layer of splanchnic mesoderm lined on its inner surface by endoderm. This cylinder is termed the archen- teron and has coimected with it the yolk-stalk and the allantois, the latter commxmicating with its somewhat dilated terminal portion, which also receives the ducts of the primitive kidneys and is known as the cloaca (Fig. 172). At a very early stage of development the anterior end of the embryo begins to project slightly in front of the yolk-sac, so that a shallow depression is formed between the two structures. As the constriction of the embryo from the sac proceeds, the anterior portion of the brain becomes bent ventrally and the heart makes its appearance immediately in front of the anterior surface of the yolk-sac, and so the depression mentioned above becomes deep- ened (Fig. 171) to form the oral sinus. The floor of this, lined by ectoderm, is immediately opposite the anterior end of the archen- teron, and, since mesoderm does not develop in this region, the ectoderm of the sinus and the endoderm of the archenteron are directly in contact, forming a thin pharyngeal membrane separating the two cavities (Fig. 171, pm). In embryos of 2.15 mm. this membrane is stiU existent, but soon after it becomes perforated and finally disappears, so that the archenteron and oral sinus become continuous. Toward its posterior end the archenteron comes into somewhat similar relations with the ectoderm, though a marked difference is 282 DEVELOPMENT OF THE DIGESTIVE TRACT 283 noticeable in that the area over which the cloacal endoderm is in contact with the ectoderm to form the cloacal membrane (Fig. .172, cm) lies a little in front of the actual end of the archenteric cyUnder, the portion of the latter which lies posterior to the mem- brane forming what has been termed the postanal gut {p. an). This diminishes in size during development and early disappears altogether, and the pouch-hke fold seen ia. Fig. 172 between the intestinal portion of the archenteron and the allantoic stalk {al) deepening until its floor comes into contact with the cloacal membrane, the cloaca becomes divided into a ventral portion, with which the allantois and the primitive excretory ducts (w) are connected, and a dorsal portion which becomes the lower end of the rectum. This latter abuts upon the dorsal portion of the cloacal membrane, and this eventually ruptures, so that the posterior communi- cation of the archenteron with the exterior becomes estab- lished. This rupture, however, does not occur until a com- paratively late period of development, imtil after the embryo has reached the fetal stage; nor does the position of the membrane correspond with the adult anus, since later there is a considerable development of mesoderm around the mouth of the cloaca, bulg- ing out, as it were, the surrounding ectoderm, more especially anteriorly where it forms the large genital tubercle (see Chapter XIII), and posteriorly where it produces the anal tubercle. This appears as a rounded elevation on each side of the median line, immediately behind the cloacal membrane and separated from the root of the caudal projection by a depression, the precaudal recess. Later the two elevations unite across the median line to form a Fig. 171. — Reconstruction of the Anterior Portion of an Embryo of 2.15 MM. 06, Aortic bulb; h, heart; o, auditory capsule; op, optic evagination; pm, pharyngeal membrane. — {His.) 284 DIGESTIVE TRACT AND GLANDS transverse ridge, the ends of which curve forward and eventually meet in front of the original and orifice. From the mesoderm of the circular elevation thus produced the external sphincter ani muscle is formed, and it would seem that so much of the lower end of the recftum as corresponds to this muscle is formed by the inner surface of the elevation and is therefore ectodermal. The definite anus being at the end of this terminal portion of the gut is there- fore some distance away from the position of the original cloacal membrane. nc Fig. 172.- — Reconstruction of the Hind End of an Embryo 6.5 mm. Long. al, AUantois; h, belly-stalk; cl, cloaca; cm, cloacal membrane; i, intestine; ». spinal cord; no, notochord; f.an, postanal gut; ur, outgrowth to formiureter and metanephros; w. Wolffian duct. — (Keibel.) It will be noticed that the digestive tract thus formed consists of three distinct portions, an anterior, short, ectodermal portion, an endodermal portion representing the original archenteron, and a posterior short portion which is also ectodermal. The differen- tiation of the tract into its various regions and the formation of the various organs found in relation with these may now be con- sidered. DEVELOPMENT OF THE MOUTH REGION 285 The Development of the Mouth Region. — The deepening of the oral sinus by the developfnent of the first branchial arch and its separation into the oral and nasal cavities by the development of the palate have already been described (p. 102), but, for the sake of continuity in description, the latter process may be briefly recalled. At first the nasal pits communicate with the oral sinus by grooves Ijdng one on each side of the fronto-nasal process, but by the union of the latter, through its processus globulares, with the maxillary processes these communications are interrupted and the floors of the nasal pits are separated from the oral cavity by thin bucco-nasal membranes, formed of the nasal epithelium in contact with that of the oral cavity. In embryos of about 15 mm. these membranes break through and disappear, and the nasal and oral cavities are again in communication, but the communications are now behind the maxillary processes and constitute what are termed the primitive choance. The oral cavity at this stage does not, however, correspond with the adult mouth cavity, since there is as yet no palate, the roof of the oral cavity being the base of the skuU. From the maxillopalatine portions of the upper jaw, shelf-like ridges begin to grow, being at first directed downward so that their surfaces are parallel with the sides of the tongue, which projects up between them. Later, however, they become bent upward to a horizontal position (Fig. 173) and eventually meet in the median line to form the palate, separating the nasal cavities from the mouth cavity. All that portion of the original oral cavity which hes behind the posterior edge of the palatal shelf is now known as the phar)Tix, the boimdary between this and the mouth cavity being emphasized by the prolongation backward and downward of the posterior angles of the palatal shelf as ridges, which form the pharyngo-palatine arches (posterior pillars of the fauces). The nasal cavities now communicate with the upper part of the pharynx (naso-pharynx) by the posterior choanas. The palatal processes are entirely derived from the maxillary processes, the premaxillary portion of the upper jaw which is a derivative of the fronto-nasal process, not taking part in their formation. Consequently a gap exists between the palatal 286 DEVELOPMENT OP THE MOUTH REGION shelves and the premaxillae for a time, by which the nasal and mouth cavities communicate; it places the organ of Jacobson (see p. 434) in communication with the mouth cavity and may persist until after birth. Later it becomes closed over by mucous membrane, but may be recognized in the dried skull as the fora- men incisivum (anterior palatine canal). Occasionally there is a failure of the union of the palatal plates, the condition known as cleft palate resulting. The inhibition of develop- ment which brings about this condition may take place at different stages, but frequently it occurs while the plates still have an almost vertical direction. Typically cleft palate is a deficiency in the median Pig. 173. — View of the Roof of the Oral Fossa of Embryo showing the Lip- Groove AND THE Formation of the Palate. — (His.) line of the roof of the mouth, not affecting the upper jaw, but very frequently it is combined with the defect which produced hare-lip (see p. 98), in which case the cleft may be continued through the upper jaw between its maxillary and premaxillary portions on either or both sides, according to the extent of the defect. At about the fifth week of development a downgrowth of epi- thelium into the substance of both the maxillary and fronto-nasal processes above and the mandibular process below takes place, and the surface of the downgrowth becomes marked by a deepen- ing groove (Fig. 173), which separates an anterior fold, the lip, from the jaw proper (Fig. 174). Mention should also be niade of the fact that at an early stage of development a pouch is formed in the median line of the roof of the oral sinus, just in front of the pharyngeal membrane, by an outgrowth of the epithelium. This DEVELOPMENT OF THE TEETH 287 pouch, known as Rathke's pouch, comes in contact above with a downgrowth from the floor of the brain and forms with it the pituitary body (see p. 403) . The Development of the Teeth. — When the epithelial down- growth which gives rise to the hp groove is formed, a horizontal outgrowth develops from it which extends backward into the sub- stance of the jaw, forming what is termed the dental shelf (Fig. 174 A). This at first is situated on the anterior surface of the jaw, but with the continued development of the hp fold it is gradually shifted until it comes to he upon the free surface (Fig. 174,5), where its superficial edge is marked by a distinct groove, the dental groove (Fig. 173). At first the dental shelf of each jaw is a con- tinuous plate of cells, uniform in thickness throughout its entire width, but later ten thickenings develop upon its deep edge, and beneath each of these the mesoderm condenses to form a dental papilla, over the surface of which the thickening moulds itself to form a cap, termed the enamel organ (Fig. 174, B). These ten papilije in each jaw, with their enamel caps, represent the teeth of the first dentition. The papillae do not, however, project into the very edge of the dental shelf, but obUquely into what, in the lower, jaw, was origi- nally its under surface (Fig. 174, B), so that the edge of the shelf is free to grow still deeper into the substance of the jaw. This it does, and upon the extension so formed there is developed in each jaw a second set of thickenings, beneath each of which a dental papilla again appears. These tooth-germs represent the incisors canines, and premolars of the permanent dentition. The lateral edges of the dental shelf being continued outward toward the arti- culations of the jaws as prolongations which are not connected with the surface epithehum, opportunity is afforded for the develop- ment of three additional thickenings on each side in each jaw, and, papilljE developing beneath these, twelve additional tooth-germs are formed. These represent the permanent molars; their forma- tion is much later than that of the other teeth, the germ of the second molar not appearing until about the sixth week after birth, while that of the third is delayed until about the fifth year. 288 DEVELOPMENT OF THE TEETH As the tooth-germs increase in size, they approach nearer and nearer to the surface of the jaw, and at the same time the enamel organs separate from the dental shelf until their connection with it is a mere neck of epithelial cells. In the meantime the dental shelf itself has been undergoing degeneration and is reduced to a reticulum which eventually completely disappears, though frag- ments of it may occasionally persist and give rise to various mal- formations. With the disappearance of the last remains of the Fig. 174. — Transverse Sections through the Lower Jaw showing the Formation of the Dental Shelf in Embryos of (A) 17 mm. and (B) 40 mm. (Rose.) shelf, the various tooth-germs naturally lose all connection with one another. It will be seen, from what has been said, that each tooth-germ consists of two portions, one of which, the enamel organ, is de- rived from the ectoderm, while the other, the dental papilla, is mesenchymatous. Each of these gives rise to a definite portion of the fully formed tooth, the enamel organ, as its name indicates DEVELOPMENT OF THE TEETH 289 producing the enamel, while from the dental papilla the dentine and pulp are formed. The cells of the enamel organ which are in contact with the sur- face of the papilla, at an early stage assume a cylindrical form and -Od. Fig. 175. — Section through the First Molar Tooth of a Rat, Twelve Days Old. Ap, Periosteum; K, dentine; Kp, epidermis; Od, odontoblasts; S, enamel; SEa and SRi, outer and inner layers of the enamel organ; SE, portion of the enamel organ which does not produce enamel. — {von Brunn.) become arranged in a definite layer, the enamel membrane (Fig. 17s, SEi), while the remaining cells (SEa) apparently degenerate eventually, though they persist for a time to form what has been termed the enamel pulp. The formation of the enamel seems to be 290 DEVELOPMENT OF THE TEETH due to the direct transformation of the enamel cells, the process be- ginning at the basal portion of each cell, and as a result, the enamel consists of a series of prisms, each of which represents one of the cells of the enamel membrane. The transformation proceeds until the cells have become completely converted into enamel prisms, except at their very tips, which form a thin membrane, the enamel cuticle, which is shed soon after the eruption of the teeth. The dental papillae are at first composed of a closely packed mass of mesenchyme cells, which later become differentiated into connective tissue into which blood-vessels and nerves penetrate. The superficial cells form a more or less definite layer (Fig. 175, ofl!), and are termed odontoblasts, having the function of manufacturing the dentine. This they accomplish in the same manner as that in which the periosteal osteoblasts produce bone, depositing the den- tine between their surfaces and the adjacent surface of the enamel. The outer surface of each odontoblast is drawn out into a number of exceedingly fine processes which extend into the dentine to oc- cupy the minute dentinal tubules, just as processes of the osteo- blasts occupy the canaliculi of bone. At an early stage the enamel membrane forms an almost com- plete investment for the dental papilla (Fig. 175), but as the ossifi- cation of the tooth proceeds, it recedes from the lower part, until finally it is confined entirely to the crown. The dentine forming the roots of the tooth then becomes enclosed in a layer of cement, which is true bone and serves to unite the tooth firmly to the walls of its socket. As the tooth increases in size, its extremity is brought nearer to the surface of the gum and eventually breaks through, the eruption of the first teeth usually taking place during the last half of the first year after birth. The growth of the per- manent teeth proceeds slowly at first, but later it becomes more rapid and produces pressure upon the roots of the primary teeth. These roots then undergo partial absorption, and the teeth are thus loosened in their sockets and are readily pushed out by the further growth of the permanent teeth. The dates and order of the eruption of the teeth are subject to con- siderable variation, but the usual sequence is somewhat as follows: DEVELOPMENT OF THE TONGUE 29I Primary Dentition. Median incisors 6th to 8th month. Lateral incisors 8th to 12th month. First molars Beginning of 2d year. Canines i J^ years. Second molars 3 to 3}4 years. Permanent Dentition First molars 7th year. Middle incisors 8th year. Lateral incisors 9th year. First premolars 10th year. Second premolars nth year. Canines y .u * *u £, J , \ 13th to 14th years. Second molars j ^ t j Third molars 17th to 40th years. In a considerable percentage of individuals the third molars (wisdom teeth) never break through the gums, and frequently when they do so theyjfail to reach the level of the other teeth, and so are only partly functional. These and other peculiarities of a structural nature shown by these teeth indicate that they are undergoing a retrogressive evolution. The Development of the Tongue. — Strictly speaking, the tongue is largely a development of the pharyngeal region of the digestive tract and only secondarily grows forward into the floor of the mouth. In embryos of about 3 mm. there may be seen in the median line of the floor of the mouth, between the ventral ends of the first and second branchial arches, a small rounded elevation which has been termed the tuber culum impar (Fig. 176, Ti). It was at one time believed that this gave rise to the anterior portion of the tongue, but recent observations seem to show that it reaches its greatest development in embryos of about 8 mm., after which it becomes less prominent and finally unrecognizable. But before this occurs a swelling appears in the anterior part of the mouth on each side of the median line (Fig. 176, t), and these gradually increase in size and eventually unite in the median line to form the main mass of the body of the tongue. They are separated from the neighboring portions of the first branchial arch by a deep groove, the alveolo-lingual groove, and posteriorly are separated 292 DEVELOPMENT OF THE TONGUE" from the second arch by a groove which later becomes distinctly V-shaped (Fig. 177), a deep depression, which gives rise to the Pig. 176. — Floor of the Mouth and Pharynx of an Embryo of 7.5 mm., from A Reconstruction. Cop. Copula; /, furcula; t, swelling that gives rise to the body of the tongue; Ti, tuberculum impar; I-III, branchial arches. thyreoid body, lying at the apex of the V. Behind the thyreoid pouch the ventral ends of the second and third branchial arches unite to form an elevation, the copula (Fig. 176, Cop), and from this and the adjacent portions of the second and third arches the posterior portion of the tongue develops. The tongue then consists of two distinct portions, which eventually fuse together, but the groove which The Floor of the Originally separated them remains more or less clearly distinguishable (Fig. 177), the vallate papillae (see p. 43 s) developing immediately an- terior to it. The tongue is essentially a muscular organ, being formed of a central mass of muscular tissue, enclosed at the sides and dorsally by mucous membrane derived from the floor of the mouth and pharynx. Fig. 177 Pharynx of an Embryo of about 20 MM. e^, Epiglottis; /c, foramen caecum; <' and f median and lateral portions of the tongue.— (i?»i.) THE SALIVARY GLANDS 293 The muscular tissue consists partly of fibers limited to the substance of the tongue and forming the m. lingualis, and also of a number of ex- trinsic muscles, the hyoglossi, genioglossi, styloglossi, glossopalatini and ckondroglossi. The last two muscles are innervated by the vagus nerve, and the remaining extrinsic muscles receive fibers from the hypoglossal, while the lingualis is supplied partly by the h)^oglossal and partly, apparently, by the facial through the chorda tympani. That the facial should take part in the supply is what might be ex- pected from the mode of development of the tongue, but the hypo- glossal has been seen to correspond to certain primarily postcranial metameres (p. 172), and its relation to structures taking part in the formation of an organ belonging to the anterior part of the pharynx seems somewhat anomalous. It may be supposed that in the evolu- tion of the tongue the extrinsic muscles, together with a certain amount of the lingualis, have grown into the tongue thickenings from regions situated much further back, for the most part from behind the last branchial arch. Such an invasion of the tongue by muscles from posterior segments would explain the distribution of its sensory nerves (Fig. 178). The anterior portion, from its position, would naturally be supplied by branches from the fifth and seventh nerves, while the posterior portion might be expected to be supplied by the seventh. There seems, how- ever, to have been a dislocation forward, if it may be so expressed, of the mucous membrane, the sensory distribution of the ninth nerve extend- ing forward upon the posterior part of the anterior portion of the tongue, while a considerable amount of the posterior portion is supplied by the tenth nerve. The distribution of the sensory fibers of the facial is probably confined entirely to the anterior portion, though further in- formation is needed to determine the exact distribution of both the motor and sensory fibers of this nerve in the tongue. The Development of the Salivary Glands. — In embryos of about 8 mm. a slight furrow may be observed in the floor of the groove which connects the lip grooves of the upper and lower jaws at the angle of the mouth and may be known as the cheek groove. In later stages this furrow deepens and eventually becomes closed in to form a hollow tubular structure, which in embryos of 17 mm. has separated from the epithelium of the floor of the cheek groove except at its anterior end and has become embedded in the con- nective tissue of the cheek. This tube is readily recognizable as the parotid gland and duct, and from the latter as it passes across the masseter muscle a pouch-like outgrowth is early formed which probably represents the soda parotidis. 294 THE SALIVARY GLANDS The submaxillary gland and duct appear in embryos of about 13 mm. as a longitudinal ridge-like thickening of the epithelium of the floor of the alveolo-lingual groove (see p. 291). This ridge gradually separates from behind forward from the floor of the groove and sinks into the subjacent connective tissue, retaining, however, its connection with the epitheUum at its anterior end, Fig. 178. — Diagram of the Distribution of the Sensory'nerves of the Tongue. The area supplied by the fifth (and seventh) nerve is indicated by the transverse lines; that of the ninth by the oblique lines; and that of the tenth by the small circles. — {Zander.) which indicates the position of the opening of the duct. In the vicinity of this there appear in embryos of 24.4 mm. five small bud-Uke downgrowths of the epithelium (Fig. 179, SL), which later increase considerably in number as well as in size, and constitute a THE SALIVARY GLANDS 295 group of glands which are generally spoken of as the sublingual gland. As these representatives of the various glands increase in length, they become lobed at their deeper ends, and the lobes later give rise to secondary outgrowths which branch repeatedly, the terminal branches becoming the alveoli of the glands. A lumen early appears in the duct portions of the structures, the alveoli remaining solid for a longer time, although they eventually also become hollow. ZAl Man. Pig. 179. — Transverse Section of the Lower Jaw and Tongue of an Embryo of about 20 mm. D, Digastric muscle; GGl., genioglossus, GH.; geniohyoid; I.Al, inferior alveolar nerve; Man, mandible; MK. Meckel's cartilage; My, mylohyoid; SL, sublingual gland; S.Mx, submaxillary duct; T, tongue. It is to be noted that each parotid and submaxillary consists of a single primary outgrowth, and is therefore a single structure and not a union of a number of originally separate parts. The sublingual glands of adult anatomy are usually described as opening upon the floor of the mouth by a number of separate ducts. This arises from the fact that the majority of the glands which form in the vicinity of the opening of Wharton's duct remain quite small, only one of them on ' each side giving rise to the sublingual gland proper. The small glands have been termed the alveolo-lingual glands, and each one of them is equivalent to a parotid or submaxillary gland. In other words, there are in reality not three pairs of salivary glands, but from fourteen to sixteen pairs, there being usually from eleven to thirteen alveolo-lingual glands on each side. 296 THE PHARYNX The Development of the Pharynx. — The pharynx represents the most anterior part of the archenteron, that portion in which the branchial arches develop, and in the embryo it is relatively much longer than in the adult, the diminution being brought about by the folding in of the posterior arches and the formation of the sinus praecervicaUs already described (p. 100). Between the vari- ous branchial arches, grooves occur, representing the endodermal portions of the grooves which separate the arches. During devel- opment the first of these becomes converted into the tympanic cavity of the ear and the Eustachian tube (see Chapter XV) ; the second disappears in its upper part, the lower persisting as the fossa in which the tonsil is situated; while the lower parts of the remaining two are represented by the sinus piriformis of the larynx (His), and also leave traces of their existence in detached portions of their epithehum which form what are termed the branchial epithelial bodies, and take part in the formation of the thyreoid and thymus glands. In the floor of the pharynx behind the thickenings which pro- duce the tongue there is to be found in early stages a pair of thick- enings passing horizontally backward and uniting in front so that they resemble an inverted U (Fig. 180, /). These ridges, which form what is termed the furcula (His), are concerned in the forma- tion of parts of the lar)mx (see p. 357). . In the part of the roof of the pharynx which comes to he between the openings of the Eusta- chian tubes, a collection of lymphatic tissue takes place beneath the mucous membrane, forming the pharyngeal tonsil, and imme- diately behind this there is formed in the median line an upwardly projecting pouch, the pharyngeal bursa, first certainly noticeable in embryos 6.5 mm. in length. This bursa has very generally been regarded as the persistent re- mains of Rathke's pouch (p. 287), especially since it is much more pronounced in fetal than in adult life. It has been shown, however, that it is formed quite independently of and posterior to the true Rathke's pouch (Killian), and Ruber's observations show that in man it represents a region of the pharyngeal epithelium with which the noto- chord retains connection after it has elsewhere separated from the endo- derm. The epithelium becomes thickened at the point of contact with THE BRANCHIAL EPITHELIAL BODIES 297 the notochord and is later drawn out into a pouch or bursa, which usually disappears after birth, but may result in the formation of a cyst in the roof of the pharynx. Structures that have been identified with the pharyngeal bursa in the embryos of other mammals, such as the pig, are, however, formed independently of any contact of the notochord with the pharyngeal epithelium. The tonsils are formed from the epithelium of the second bran- chial groove. At about the fourth month solid buds begin to grow from the epithelium into the subjacent mesench3Tiie, and depressions appear on the surface of this region. Later the buds become hollow by a cornification of their central cells, and open upon the floor of the depressions which represent the crypts of the tonsil. In the meantime lymphocytes, concerning whose origin there is a difference of opinion, collect in the subjacent mesenchyme and eventually aggregate to form lymphatic folli- cles in close relation with the buds. Whether the lymphocytes wander out from the blood into the mesenchyme or are derived directly from the epitheKum or the mes- enchyme cells is the question at issue. The tonsil may grow to a size suflScient to fill up completely the groove in which it forms, but not infrequently a marked depression, the fossa supraionsillaris, ex^ ists above it and represents a portion of the original second branchial furrow. The groove of RosenmuUer, which was at one time thought to be also a remnant of the second furrow, is a secondary de- fig. i 80.— The Floor . 1 • 1 • I, jr - OF THE Pharynx of an pression which appears m embryos of 11.5 ^^^^^^ of 2.15 mm. cm. behind the opening of the Eustachian f_ Furcuia; t. tubercuium tube, in about the region of the third impar.— (His.) branchial furrow. The Development of the Branchial Epithelial Bodies. — These are structures which arise either as thickenings or as outpouchings of the epithelium lining the lower portions of the inner branchial furrows. Five pairs of these structures are developed and, in addition, there is a single unpaired median body. This last makes 298 THE BRANCHIAL EPITHELIAL BODIES its appearance in embryos of about 3 mm., and gives rise to the major portion of the thyreoid body. It is situated immediately behind the anterior poi^ion of the tongue, at the apex of the groove between this and the posterior portion, and is first a slight pouch- like depression. As it deepens, its extremity becomes bilobed, and after the embryo has reached a length of 7 mm. it becomes com- pletely separated from the floor of the pharynx. The point of its original origin is, however, permanently marked by a circular depression, the foramen ccBcum (Fig. 177, /c). Later the bilobed body migrates down the neck and becomes a sohd transversely elongated mass (Fig. 181, th), into the substance of which tra- ptAf Fig. 181. — Reconstructions of the Branchial Epithelial Bodies of Embryos. of {a) 14 mm. and (b) 26 mm. ao. Aorta; llh, lateral thyreoid; ph, pharynx; pth^ and pth^, parathyTeoids; '' /■' I \ i ' jl ; 1 I ,. j^ 1 -; D* / ' S / ^ \ \ / ,' i V / ,' y \ 6 : .-" •^ _,, '' ^' « J ~ II AGE 2 3 4- 5 a 7 a > » / i jg i 9 ji « S t p /7 ^ t |- Lbst4- \ - an , \ ^ ■■ *N \ i, . i -\ ^ / A ^ ^ _, i''. ^ \ ^'- *j •f \ ., ^ •^ ? >v i 1 L' ^, ,, ' \ "" ■~ ~ ~ ~ \ ^ _, ^ Pig. 287. — Curves Showing the Annual Increase in Weight in (I) Boys and (.II) Girls. The taint line represents the curve from British statistics, the dotted line that from American (Bowditch), and the heavy line the average o£ the two. Before the fixth year the data are unreliable. — (Stephenson.) to note to what extent the organs which are more immediately associated with the metabolic activities of the body undergo a rela- tive reduction in weight. The most important of these organs is undoubtedly the liver, but with it there must also be considered the thyreoid and thymus glands, and probably the suprarenal bodies. 48o POST-NATAL DEVELOPMENT In all these organs there is a marked diminution in size as com- pared with the weight of the body, as will be seen from the follow- ing table (H. Vierordt), which also includes data regarding other organs in which a marked relative diminution, not in all cases readily explainable, occurs. ABSOLUTE WEIGHT IN GRAMS New-born and Adult Liver Thy- reoid Thy- mus Suprarenal Bodies Spleen Heart Kidney Brain Spinal Cord 141-7 1,819.0 4.85 33-8 8. IS 26.9 70s 7-4 10.6 163.0 23.6 300.6 233 305-9 381.0 1,430-9 S-S 39-15 PERCENTAGE WEIGHT OF ENTIRE BODY New-born and Adult Liver Thy- Thy- reoid mus Suprarenal Bodies Spleen Heart Kidney Brain spinal Cord 4-S7 2-S7 0. 16 o.os 0. 26 0.04 0.23 O.OI 0-34 0.2s 0. 76 0.46 0.7s 0.46 12.29 2.16 0.18 0.06 Recent observations by Hammar render necessary some modifica- tion of the figures given for the thymus in the above table. He finds the average weight of the gland at birth to be 13.26 grams, and that the weight increases up to puberty, averaging 37.52 grams between the ages of II and 15. After that period it gradually diminishes, falling to 16.27 grams between 36 and 45, and to 6.0 grams between 66 and 75. Expressed in percentage of the body weight this gives a value in the new-born of 0.42 and in an individual of 50 years of 0.02, a difference much more striking than that shown in Vierordt's table. It must be mentioned, however, that the gland is subject to much individual variation, being largely influenced by nutritive conditions. The remaining organs, not included in the tables given above when compared with the weight of the body, either show an in- crease or remain practically the same. POST-NATAL DKVELOPMENT 481 ABSOLUTE WEIGHT IN GRAMS New-born and Adult Skin and Sub- cutaneous Tissues Skeleton Musculature Stomach and Intestines Pancreas Lungs 611.7s 11,765.0 42s -S ii,S7S-o 776. S 28,732.0 65 1,364 3.5 97.6 54-1 994-9 PERCENTAGE OF BODY WEIGHT New-born and Adult Skin and Sub- cutaneous Tissues Skeleton Musculature Stomach and Intestines Pancreas Lungs 19-73 17.77 13-7 17.48 25. 05 43-40 2.1 2.06 O.II o.IS I -75 1-5° From this- table it will be seen that the greatest increment of weight is that furnished by the muscles, the percentage weight of which is one and three-fourths times as great in the adult as in the child. The difference does not, however, depend upon the differ- entiation of additional muscles; there are just as many muscles in the new-born child as in the adult, and the increase is due merely to an enlargement of organs already present. The percentage weight of the digestive tract, pancreas, and lungs remains practically the same, while in the case of the skeleton there is an appreciable in- crease, and in that of the skin and subcutaneous tissue a slight diminution. The latter is readily understood when it is remem- bered that the area of the skin, granting that the geometric form of the body remains the same, would increase as the square of the length, while the mass of the body would increase as the cube, and hence in comparing weights the skin might be expected to show a diminution even greater than that shown in the table. The increase in the weight of the skeleton is due to a certain extent to growth, but chiefly to a completion of the ossification of the cartilage largely present at birth. A comparison of the weights of this system of organs does not, therefore, give evidence of the many changes of form which may be perceived in it during 482 POST-NATAL DEVELOPMENT the period under consideration, and attention may be drawn to some of the more important of these changes. In the spinal column one of the most noticeable pecularities observable in the new-born child is the absence of the curves so characteristic of the adult. These curves are due partly to the weight of the body, transmitted through the spinal column to the hip-joint in the erect position, and partly to the action of the mus- FiG. 288. — ^Longitudinal Section through the Sacrum of a New-born Female Child. — (Fehling.) cles, and it is not until the erect position is habitually assumed and the musculature gains in development that the curvatures become pronounced. Even the curve of the sacrum, so marked in the adult, is but slight in the new-born child, as may be seen from Fig. 285, in which the ventral surfaces of the first and second sacral vertebrae look more ventrally than posteriorly, so that there is no distinct promontory. POST-NATAL DEVELQPMENT 483 But, in addition to the appearance of the curvatures, other changes also occur after birth, the entire column becoming much more slender and the proportions of the lumbar and sacral vertebras becoming quite different, as may be seen from the following table (Aeby): LENGTHS OF THE VERTEBRAL REGIONS EXPRESSED AS PERCENT- AGES OF THE ENTIRE COLUMN Age Cervical Thoracic Lumbar New-born child . . 25.6 233 20,3 19.7 22. ± 47-S 46.7 4S-6 47.2 46.6 26 8 30.0 34-2 33- 1 31.6 IMeIc 5 years , . The cervical region diminishes in length, while the lumbar gains, the thoracic remaining approximately the same. It may be noticed, furthermore, that the difference between the two variable regions is greater during youth than in the adult, a condition possi- bly associated with the general more rapid development of the lower portion of the body made necessary by its imperfect develop- ment during fetal life. The difference is due to changes in the vertebrae, the intervertebral disks retaining approximately the same relative thickness throughout the period under consideration. The form of the thorax also alters, for whereas in the adult it is barrel-shaped, narrower at both top and bottom than in the middle, in the new-born child it is rather conical, the base of the conejbeing below. The difference depends upon slight differences in the form and articulations of the ribs, these being more horizon- tal in the child and the opening of the thorax directed more directly upward than in the adult. As regards the skull, the processes of growth are very compli- cated. Cranium and brain react on one another, and hence, in harmony with the relatively enormous size of the brain at birth, the cranial cavity has a relatively greater volume in the child than in the adult. The fact that the entire roof and a considerable part of the sides of the skull are formed of membrance bones which, at 484 POST-NATAL DEVELOPMENT birth, are not in sutural contact with one another throughout, gives opportunity for considerable modifications, and, furthermore, the base of the skull at the early stage still contains a considerable amount of unossified cartilage. Without entering into minute de- tails, it may be stated that the principal general changes which the skull undergoes in its post-natal development are (i) a relative elongation of its anterior portion and (2) an increase in the relative height of the maxillae . If a line be drawn between the central points of the occipital condyles, it will divide the base ol the skull into two portions, Fig. 289. — Skull of a New-born Child and of an Adult Man, Drawn as of Approximately the Same Size. — {Henke.) which in the chUd's skull are equal in length. The portion of the skull in front of a similar line in the adult skull is very much greater than that which lies behind, the proportion between the two parts being 5:3, against 3 : 3 in the child (Froriep) . There has, therefore, been a decidedly more rapid growth of the anterior portion of the skull, a growth which is associated with a cor- responding increase in the dorso-ventral dimensions of the maxillse. These bones, indeed, play a very important part in determining proportions of the skull at different periods. They are so the intimately associated with the cranial portions of the skull that their increase necessitates a corresponding increase in the anterior part of the cranium, and their increase in this direction stands in relation to the development of the teeth, the eight teeth which are developed in each maxilla (including the premaxilla) in the adult re- POST-NATAL DEVELOPMENT 485 quiring alonger bone than do the five teeth of the primary dentition, these again requiring a greater length when completely developed than they do in their immature condition in the new-born child. But far more striking than the difference just described is that in the relative height of the cranial and facial regions (Fig. 289). It has been estimated that the volumes of the two portions have a ratio of 8 : 1 in the new-born child, 4 : i at five years of age, and 2:1 in the adult skull (Froriep), and these differences are due principally to changes in the vertical dimensions of the maxillas. As with the increase in length, the increase now under consideration is, to a certain extent at least, associated with the development of the teeth, these structures calling into existence the alveolar proc- esses which are practically wanting in the child at birth. But a more important factor is the development of the maxillary sin- uses, the practically solid bodies of the maxillae becoming trans- formed into hollow shells. These cavities, together with the sinuses of the sphenoid and frontal bones, which are also post-natal developments, seem to stand in relation to the increase in length of the anterior portion of the skull, serving to diminish the weight of the portion of the skull in front of the occipital condyles and so relieving the muscles of the neck of a considerable strain to which they would otherwise be subjected. These changes in the proportions of the skull have, of course, much to do with the changes in the general proportions of the face. But the changes which take place in the mandible are also impor- tant in this connection, and are similar to those of the maxillae in being associated with the development of the teeth. In the new- born child the horizontal ramus is proportionately shorter than in the adult, while the vertical ramus is very short and joins the horizontal one at an obtuse angle. The development of the teeth of the primary dentition, and later of the three molars, necessi-' tates an elongation of the horizontal ramus equivalent to that occurring in the maxillae, and, at the same time, the separation of the alveolar borders of the two bones requires an elongation of the vertical ramus if the condyle is to preserve its contact with the mandibular fossa, and this, again, demands a diminu- 486 POST-NATAL DEVELOPMENT tion of the angle at which the rami join if the teeth of the two jaws are to be in proper apposition. In the bones of the appendicular skeleton secondary epiphy- sial centers play an important part in the ossification, and in few are these centers developed prior to birth, while the union of the epiphyses to the main portions of the bones take place only to- ward maturity. The dates at which the various primary and sec- ondary centers appear, and the time at which they unite, may be seen from the following table: UPPER EXTREMITY Bone Appearance of Appearance of Secondary Fusions of Primary Center Centers Centers Clavicle 6th week. (At sternal end) 17th year. 20th year. Scapula. Body Sth week. 2 acromial isth year. 2 on vertical border i6th year. 20th year. Coracoid ist year. I Sth year. Head ist year. Great tuberosity 3d year. 20th year. Lesser tuberosity 5th year. Humerus ytk week. Inner condyle sth year. Capitellum 3d year. I Sth year. Trochlea loth year. 17th year. Outer condyle 14th year. Ulna '/tk week. Olecranon loth year Distal epiphysis 4th year. i6th year. iSth year. Radius yth week. Proximal epiphysis sth year. 17th year. Distal epiphysis 2d year 20th year. Capitatum. . . . ist year. Hamatum 2d year. Triquetrum . . . Lunatum 3d year. 4th year. Multangulum Sth year. majus. Navicular 6th year. Multangulum Sth year. minus. Pisiform 12th year. Metacarpals . . 3d year. 20th year. Phalanges glh-iith week. 3d-sth years. i7th-i8th years. The dates in italics are before birth. POST-NATAL DEVELOPMENT LOWER EXTREMITY 487 Bene Appearance of Pnmary Centei Appearance of Seconadry Centers Fusion of Centers Ilium gth week. ^h month. 4th month. Cartilage appear ^th week. yth week. Sth week. yth month. 6th month. A few days after birth. 4th year. ist year. gth week. gth-i2th week. Crest 15th year. Anterior inferior spine 15th year. Tuberosity isth year. Crest I Sth year. s at 4th month, ossification in 3d y< Head ist year. Great trochanter 4th year. Lesser trochanter i3th-i4th year Condyle gth month Head end of gth month. Distal end 2d year. Upper epiphysis sth year. Lower epiphysis 2d year. loth year. 3d year. 4th-8th years ^ Ischium Pubis 2 2d year. Patella Femur Tibia ;ar. 20th year. 19th year. 1 8th year. 2 ist year. 2ist-25th year. Fibula Talus 1 Sth year. 2 ist year. 20th year. Calcaneus Cuboid Navicular Cuneiforms- . . . Metatarsals . . . Phalanges 1 6th year. 20th year. I7th-i8th years The dates in italics are before birth. So far as the actual changes in the form of the appendicular bones are concerned, these are most marked in the case of the lower Umb. The ossa innominata alter somewhat in their proportions after birth, a fact which may conveniently be demonstrated by con- sidering the changes which occur in the proportions of the pelvic diameters, although it must be remembered that these diameters are greatly influenced by the development of the sacral curve. Taking the conjugate diameter of the pelvic brim as a unit for com- parison, the antero-posterior (dorso-ventral) and transverse diame- ters of the child and adult have the proportions shown in the table on the opposite page (Fehling). It will be seen from this that the general form of the pelvis in the new-born child is that of a cone, gradually" diminishing in diameter from the brim to the outlet, a condition very different 488 POST-NATAL DEVELOPMENT from what obtains in the adult. Furthermore, it is interesting to note that sexual differences in the form of the pelvis are clearly distinguishable at birth; indeed, according to Fehling's obser- vations, they become noticeable during the fourth month of intra- uterine development. Diameter New-bom Female Adult Female New-bom Male Adult Male Coniusrata vera I.oo 1. 19 0.96 1 .01 o.gi 0.83 1.00 1.292 1. 19 1. 151 I -OS 1. 154 1.00 I. 2C 0.91 0.99 0.78 0.84 I 00 1.294 I 18 t>N Antero-Dosterior . CJ Transverse 1. 14 1.07 I 153 1 "^'■"P"^^"'''^ 3 The upper epiphysis of the femur is entirely unossified at birth and consists of a cartilaginous mass, much broader than the rather slender shaft and possessing a deep notch upon its upper surface (Fig. 290). This notch marks off the great trochanter from the head of the bone, and at this stage of development there is no neck, the head being practically sessile. As development proceeds the inner upper portion of the shaft grows more rapidly than the outer portion, carrying the head away from the great trochanter and forming the neck of the bone. The acetabulum is shallower at birth than in the adult and cannot contain more than half the head of the femur; consequently the articular portion of the head is much less extensive than in the adult. It is a well-known fact that the new-born child habitually holds the feet with the soles directed toward one another, a position only reached in the adult with some difi&culty, and associated with this supination or inversion there is a pronounced extension of the foot (i.e., flexion upon the leg as usually understood; see p. 104), it being difficult to flex the child's foot beyond a line at right angles with POST-NATAL DEVELOPMENT 489 the axis of the leg. These conditions are due apparently to the extensor and tibialis muscles being relatively shorter and the oppos- ing muscles relatively longer than in the adult, and with the elon- gation or shortening, as the case may be, of the muscles on the assumption of the erect position, the bones in the neighborhood of the ankle-joint come into new relations to one another, the result being a modification of the form of the articular surfaces, especially of the talus (astragalus). In the child the articular cartilage of the trochlear surface of this bone is continued onward to a consid- erable extent upon the neck of the bone, which comes into contact Fig. 290. — Longitudinal Sections of the Head of the Pemur of (A) New BORN Child and (J3) a Later Stage of Development. with the tibia in the extreme extension possible in the child. In the, adult, however, such extreme extension being impossible, the cartilage upon the neck gradually disappears. The supination in the chUd brings the talus in close contact with the inner surface of the calcaneus and with the sus tenaculum tali; with the alteration of position a growth of these portions of the calcaneus occurs, the sustentaculum becoming higher and broader, and so becoming an obstacle in the way of supination in the adult. At the same time a greater extent of the outer surface of the talus comes into contact with the lateral malleolus, with the result that the articular surface 490 LITERATURE is considerably increased on that portion of the bone. Marked changes in the form of the talo-navicular articulation also occur, but their consideration would lead somewhat further than seems desirable. LITERATURE C. Aeby: "Die Altersverschiedenheiten der menschlichen WirbelsSuIe." Archiv fiir Anal, und Physiol., Anat. Abih., 1879. W. Camerer: " Utersuchungen uber Massenwachsthum und Langenwachsthum der Kinder," Jahrbuchfiir Kinderheilkunde, xxxvi, 1893. H. H. Donaldson: "The Growth of the Brain," London, 1895. H. Fehling : " Die_Form des Beckens beim Fotus und Neugeborenen und ihre Bezie- hung zu der beim Erwachsenen," Archiv fiir Gynakol., x, 1876. H. Friedenthal: "Das Wachsthum des Korpergewichtes des Menschen und anderer Saugethiere in verschiedenen Lebensaltern," Z^eit. allgem. Physiol., IX, 1909. J. A. Hammar: "Ueber Gewicht, Involution und Persistenz der Thymus im Post- fotalleben des Menschen," Archiv fiir Anat. und Phys., Anat. Abth., Supplement, 1906. W. Henke: "Anatomie des Kindersalters," Handbuch der Kinderkrankheiten {Ger- hardt), Tubingen, 1881. C. Hennig: "Das kindliche Becken," Archiv fiir Anat. und Physiol., Anal. Abth., 1880. C. HtJTER: "Anatomische Studien an den Extremitatengelenken Neugeborener und Erwachsener," Archiv fiir patholog. Anat. und Physiol., xxv, 1862. W. Stephenson: "On the Relation of Weight to Height and the Rate of Growth in Man," The Lancet, 11, 1888. R. Thoma: " Untersuchungen uber die Grosse und das Gewicht der anatomischen Bestandtheile des menschlichen Korpers," Leipzig, 1882. H. Vierordt: "Anatomische, Physiologische und Thysikalische Daten und Tabel- len," Jena, 1893. H. Welcker: "Untersuchungen uber Wachsthum und Bau des menschlichen Schadels," Leipzig, 1862. INDEX After-birth, 140 After-brain, 390 Age of embryos, 105 Agger, nasi, 179 Allantois, 112, 116, 364 Alveolo-lingual glands, 29s groove, 291 Amitotic division, 7 Amnion, iii, it2 Amniotic cavity, S7 Amphiarthrosis, 190 Ampliiaster, 5 Angioblast, 222 Aimulus of Vieussens, 235 Anterior commissure, 410 Anthelix, 450 Antitragus, 450 Anus, 283 Aortic arches, 245 bulb, 232 septum, 237 Archenteron, 51, 282 Archoplasm sphere, 4 Arcuate fibers, 394 Areas of Langerhans, 315 Arrectores pilorum, 149 Arteries, 241 anterior tibial, 255 aorta, 246 branchial, 243 carotid, 244 centralis retinae, 463 cceliac, 248 common iliac, 246, 252 costo-cervical, 251 dorsalis pedis, 256 epigastric, 25r external iliac, 249 maxillary, 244 Arteries, femoral, 255 hyaloid, 452 hypogastric, 249, 269 inferior gluteal, 256 inferior mesenteric, 248 innominate, 246 intercostal, 246 internal mammary, 251 maxillary, 244 spermatic, 247 interosseous, 252, 255 lingual, 244 lumbar, 246 median, 252 middle sacral, 247 peroneal, 256 popliteal, 25 s posterior tibial, 255 profunda femoris, 255 pulmonary, 245 radial, 254 renal, 247 sciatic, 255 subclavian, 246, 252 superficial radial, 252 superior mesenteric, 248 vesical, 249 temporal, 244 ulnar, 252 umbilical, 119, 243, 248 vertebral, 249 vitelline, 224 Articular capsule, 190 Ary-epiglottic folds, 338 Arytenoid cartilages, 339 Aster, s Atresia of duodenum, 309 of pupil, 4S7 Atrial septum, 234 Atrio-ventricular bundle, 240 valves, 239 491 492 INDEX Auerbach, plexus of, 425 Auricle, 449 Axis cylinder, 382 £ Bartholin, glands of, 367 Belly-stalk, 72, 116 Bile capillaries, 311 Bladder, 366 Blastoderm, 45 Blastopore, 51, S7. 59 Blastula, 42 Blood, 226 islands, 223 platelets, 230 vessels, 222 Body cavity, 62 Bone, development of, 156 growth of, 159 Bone-marrow, 158 Bones : atlas, 165, 167 axis, 167 carpal, 187, 190, 486 clavicle, 185, 486 coccyx, 168 conchas, 178 epistropheus, 165, 167 ethmoid, 177 femur, i8g, 487, 488 fibula, 189, 487 frontal, 180 humerus, 187, 486 hyoid, 184 ilium, 188, 487 incus, 182, 445 innominate, 188, 487 Interparietal, 175 ischium, 188, 487 lachrymal, 180 malleus, 182, 445 mandible, 182 maxilla, 181 metacarpal, 188, 486 metatarsal, 190, 487 nasal, 180 Bones: occipital, 172, 17s palatine, 181 parietal, 180 patella, i8g, 487 periotic, 171, 179 phalanges, 188, 190, 486, 487 precoracoid, 191 premaxilla, 181 pubis, 188, 487 radius, 187, 486 ribs, i64j 167 sacrum, 168, 482 scapula, 186, 486 sphenoid, 176 stapes, 446 sternum, 168 suprasternal, 169 tarsal, 189, 487, 488 temporal, 179 tibia, 189, 487 turbinated, 178 ulna, 187, 486 vertebrae, 162, 166, 483 vomer, 178 zygomatic, 180 Brachia conjunctiva, 398 Brain, 390, 480 Branchial arches, 93, 99 clefts, 93 epithelial bodies, 296, 297 fistula, 94 Branchiomeres, 84 Bronchi, 335 Bucconasal membrane, 285 Bulbo-urethral glands, 367 Bulbo-vestibular glands, 367 Burdach, fasciculus of, 389 Bursa omentalis, 327 Caecum, 304, 307 Calcar, 408 Canal, inguinal, 371 of Cloquet, 467 of Gartner, 361 of Nuck, 369 INDEX 493 Canal of Petit, 467 Canalized fibrin, 130 Capillaries, 224 Cartilages of Santorini, 339 of Wrisberg, 339 Caruncula lacrimalis, 472 Cauda equina, 388 Caul, IIS Cell, I, 3 division, 5 theory, i Centrosome, 4 Cerebellum, 396 Cerebral aqueduct, 399 convolutions, 407 cortex, 412 hemispheres, 404 peduncles, 398, 399 Charcot, crystalloid of, 14 Cheek groove, 293 Chin ridge, 103 Chondrioconts, s Chondriosomes, 5 Chondrocranium, 172, 17s Chorda canal, 60 dorsalis, 78 endoderm, 78 Chorioid coat, 454, 467 plexus, 393, 401, 406 Chorioidal fissure of brain, 406 of eye, 452, 457 Chorion, 71, 121 frondosum, 127 laeve, 127 Chorionic villi, 126 ChromaflSne organs, 374 ^ Chromatin, 4 Chromosomes, s reduction of, is, 30 Ciliajy body, 4S8 ganglion, 429 muscle, 469 Cleft palate, 286 sternum, 171 Clitoris, 367 Cloaca, 282, 363 Cloacal membrane, 283 Cloquet, canal of, 467 Coccygeal ganglion, 276 Coelom, SI 62, 73, 81 Collateral eminence, 409 CoUiculus seminalis, 362 Coloboma, 458 Colon,- 306 Colostrum, 1S3 Conjunctiva, 469 Connective tissues, iss Cornea, 453, 468 Corniculate cartilages, 338 Corona radiata, 21, 357 Coronary sinus^ 234, 260 Corpora mammillaria, 402 quadiigemina, 399 Corpus albicans, 24 callosum, 410 luteum, 23 striatum, 404 Corti, spiral organ of, 441 Cowper, glands of, 367 Cranial nerves, 414 sinuses, 2S7 Cricoid cartilage, 339 Cuneiform cartilages, 338 Cutis plate, 83 Cytoplasm, 3 Cyto-trophoblast, 57, 12s D Darwin's tubercle, 4S0 Decidua basalis, 132, 13s capsularis, 124, 133, 134 reflexa, 124, 133 serotina, 132 vera, 132, 133 Decidual cells, 134, 140 Dendrites, 382 Dental groove, 287 papilla, 287 shelf, 287 Dentate gyrus, 408 Dermatome, 83 Descent of ovary, 369 of testis, 370 494 INDEX Diaphragm, 323 Diarthrosis, 191 Diencephalon, 390, 399 Discus proligerus, 20, 357 Double monsters, 49 ' Duct of Santorini, 315 of Wrisberg, 315 Ductus arteriosus, 245, 269 Botalli, 24s choledochus, 310 cochlearis, 439 Cuvieri, 259 ejaculatorius, 359 endolymphaticus, 437 reuniens, 439 venosus, 262 Duodenum, 305, 306, 309 Ear, 436 Ebner, glands of, 436 Ectoderm, 51 Embryo, age of, 105 external form, 89 growth of, 477 Embryonic disc, S7 Embryotroph, 125 Enamel organ, 287, 289 Enchylema, 4 Endocardium, 230 Endoderm, 51, 54, 57 Enveloping layer, 45, 48 Ependymal cells, 381 Epiblast, SI Epibranchial placodes, 422 Epidermis, 143 Epididymis, 358 Epiglottis, 338 Epiphyses, 158 Epiphysis cerebri, 400 Epiploic foramen, 327 Episternal cartilages, 169 Epitrichium, 143 Eponychium, 147 Epoophoron, 360 Erythrocytes, 226, 227 Erythroplastids, 227 Eustachian tube, 296, 4/^4 valve, 23 s Extrauterine pregnancy, 23 Eye, 451 Eyelids, 469 Fallopian tubes, 361 Fasciculus communis, 419 of Burdach, 389 of GoU, 388 solitarius, 393, 419 Fenestra cochlese, 444 ovalis, 444 rotunda, 444 vestibuli, 444 Fertilization of ovum, 31 Fetal circulation, 267 Fibrinoid, 130 Fifth ventricle, 411 Filum terminale, 388 Fimbria, 410 ovarica, 362 Foliate papillae, 436 Fontana, spaces of, 469 Foramen caecum, 298 of Winslow, 327 ovale, 234, 241 Fore-brain, 390 Formatio reticularis, 394 Fornix, 410 Frontal sinuses, 178 Funiculus cuneatus, 389 gracilis, 388 Furcula, 296, 337 Gartner, canals of, 361 Gall bladder, 310 GangUonated cord, 427 Gastral mesoderm, 53, 61 Gastrula, 5r Geniculate bodies, 401 Genital folds, 367 ridge, 341, 3S3 INDEX 495 Genital swelling, 367 tubercle, 367 Germ cells, 8 layers, 50, 63 plasm, 8 Giraldes, organ of, 358 Glands of Bartholin, 367 bulbo-urethral, 367 bulbo-vestibular, 367 of Cowper, 367 of Ebner, 436 Meibomian, 470 of Moll, 470 salivary, 293 tarsal, 470 Goll, fasciculus of, 388 Graafian follicle, 19 Great omentum, 327 Groove of Rosenmiiller, 297 Gubernaculum testis, 360 Gynaecomastia, 153 H Hsemoblasts, 222 Heematopoietic organs, 226 Haemolymph nodes, 275 Hairs, 148 Hare lip, 102, 182 Hassall's corpuscles, 300 Haversian canals, 160 Head cavities, 82 process, 59, 72 Heart, 230, 480 Helix, 450 Hensen's node, 59 Hermaphroditism, 369 Hind-brain, 390 Hippocampus, 408 Hyaloid canal, 467 Hydatid of Morgagni, 359 stalked, 362 Hydramnios, 1x5 Hymen, 362 Hyperthelia, 152 Hypertrichosis, 150 Hypoblast, 51 Hypochordal bar, 163 Hypophysis, 403 Hypospadias, 369 Hypothalamic region, 401 I Idiochromosomes, 16, 34 Iliac lymph sac, 270 Implantation of ovum, 121 Infracardial bursa, 327 Infundibulum, 404 Inguinal canal, 371 Iimer cell mass, 48 Insula, 409 Interarticular cartilages, 191 Intercarotid ganglion, 377 Intermediate cell mass, 80 Interrenal organs, 374 Interventricular foramen, 405 Intervertebral fibro-cartilage, 162, 164 Intestine, 304, 48X Iris, 458 Isthmus cerebri, 390, 398 Jacobson, organ of, 434 Joints, 190 Jugular lymph sac, 270 K Karyokinesis, 7 Karyoplasm, 3 Kidney (see Metanephros), 347, 480 Labia majora, 368 minora, 368 Lachrymal gland, 471 Lamina terminalis, 402 Langerhans, areas of, 315 Langhans cells, 129 Lanugo, 149 Larynx, 337 Lateral thyreoids, 301 Lens, 4S2, 454 496 INDEX Lesser omentum, 326 Leukocytes, 229 Ligaments: broad, of uterus, 352, 360 coraco-humeral, 217 coronary, of liver, 324 falciform, of liver, 324 fibular lateral, of knee, 201 flavan, 164 inguinal, 353, 360, 362 interspinous, 164 mucosum, 192 of the ovary, 362 pectinatum iridis, 469 round, of liver, 270 round, of uterus, 362 sacro-tuberous, 201 spheno-mandibular, 184 suspensory of lens, 466 Limbs, 93, 103 Lip-ridge, 103 Lips, 286 Liver, 309, 480 Lubarsch, crystalloid of, 14 Lungs, 334, 481 Luschka's ganglion, 276 Lymphatics, 270 Lymph nodes, 273 sacs, 270 Lymphocytes, 229, 276 M Magma, cellular, 68 reticular, 70 Mammary gland, 150 Mandibular process, 94 Mastoid cells, 447 Maturation of ovum, 28 Maxillary antrum, 178 process, 94 Meckel's cartilage, 173, 182 diverticulum, 116, 307 Mediastina, 325 Medulla oblongata, 390 Medullary canal, 77, 90 cords, 356 Medullary folds, 75 groove, 73 sheath, 386 Megacaryocytes, 230 Meibomian glands, 470 Meissner, plexus of, 425 Membrana pupiUaris, 457 reuniens, 84 tectoria, 442 Membrane bone, 156 Menstruation, 26 Mesencephalon, 390, 398 Mesenchyme, 64 Mesenteriole, 330 Mesentery, 326 Mesocardium, 319 Mesocolon, 328 Mesoderm, 51 somatic, 80 splanchnic, 81 ventral, 80 Mesodermic somites, 75, 79 Mesogastrium, 326 Mesonephros, 345, 358 Mesorchium, 359, 371 Mesothelium, 64 Metamere, 86 Metanephros, 347 Metencephalon, 390, 395 Mid-brain, 390 Middle ear, 444 Milk ridge, i$o Mitochondria, 5 Mitosis, 7 Moll, glands of, 470 Montgomery's glands, 151 Morgagni, hydatid of, 359 Morula, 46 Mouth cavity, 285 Mullerian duct, 351 Muscle plates, 83 Muscles: arrectores pilorum, 149 biceps femoris, 217 branchiomeric, 207 chondroglossus, 211 ciliary, 469 INDEX 497 Muscles: coccygeus, 206 constrictor of pharynx, 209, 361 cranial, 206 curvator coccygis, 206 depressors of hyoid, 203 digastric, 209 dilatator iridis, 459 dorsal, 202 eye, 207 facial, 209 gastrocnemius, 215, 2ig geniohyoid, 2oy genioglossus, 203 glosso-palatinus, 209 hyoglossus, 204 hjrposkeletal, 204 intercostal, 204 laryngeal, 209, 340 latissimus dorsi, 200, 216 levator ani, 206 limb, 211 longus capitis, 204 colli, 204 lumbrical, 219 masseter, 209 mylohyoid, 209 obliqui abdominis, 204 occipito-frontalis, 201, 209 omohyoid, 200 pectorals, 216 perineal, 206 peroneus longus, 217 platysma, 209 pronator quadratus, 217 psoas, 204 pterygoids, 209 pyramidalis, 203 rectus abdominis, 201, 203 sacro-spinalis, 201, 204 scaleni, 204 serrati posteriores, 201 serratus anterior, 201, 216 skeletal, 199 soleus, 215, 219 sphincter ani, 206 sphincter cloacae, 206 32 Muscles: sphincter cloacae, 206 iridis, 459 stapedius, 209, 446 sternohyoid, 200 sternomastoid, 200, 204, 211 styloglossus, 204 stylohyoid, 209 stylopharyngeus, 209, 301 temporal, 209 tensor tympani, 209, 445 veli palati, 209 transversus abdominis, 204 thoracis, 204 trapezius, 200, 204, 211 Muscle tissue, 195 Myelencephalon, 390, 393 Myelin, 386 Myelocytes, 229 Myoblasts, 197 Myocardium, 230 Myotome, 83, 199 N Nails, 14s Nape bend, 93 Nasal pit, loi process, loi Naso-lachrymal duct, 471 NephrogetSc cord, 346 Nephrostome, 344 Nephrotome, 83 Nerve components, 415, 418, 421 roots, 384 Nerves: auditory, 420 cranial, 414 hypoglossal, 417 olfactory, 433 optic, 462 recurrent, 340 spinal, 413 accessory, 421 splanchnic, 429 terminal, 417 Nerve tissue, 381 Neural crest, 384 498 INDEX Neurenteric canal, 6i, 73, 76 Neuroblasts, 382 Neuroglia cells, 382 Neuromeres, 423 Neurone theory, 386 Nitabuch's stria, 139 Non-sexual reproduction, 9 Normoblasts, 227 Notochord, 77 Nuck, canal of, 369 Nucleoli, 4 Nucleus, 3 O Odontoblasts, 290 CEsophagus, 301 CEstrus, 28 Olfactory lobes, 411 organ, 433 Olivary body, 394 Omentum, 327 Oocyte, 29 Optic cup, 452. 457 recess, 402 Oral fossa, 91, loi, 282 Organ of Giraldes, 358 of Jacobson, 434 of Rosenmiiller, 360 Organs, 3 chromaffine, 374 interrenal, 374 of taste, 435 of Zuckerkandl, 378 suprarenal, 374, 480 Osteoblasts, 156 Osteoclasts, 160 Otocyst, 437 Otic ganglion, 429 Ovary, 356 descent of, 369 Ovulation, 22, 26 Ovum, 19 fertilization of, 31 implantation of, 121 maturation of, 28 segmentation of,*4i Palate, 285 Pancreas, 314, 481 Paradidymis, 358 Paraphysis, 400 Parathymus, 301 Parathyreoid bodies, 299 Paroophoron, 360 Parotid gland, 293 Parovarium, 360 Parthenogenesis, 9 Penis, 368 Pericardial cavity, '320, 321 Perineal body, 366 Perionyx, 147 Periosteum, 157 Periotic capsule, 171, 178 Peritoneum, 326 Petit, canal of, 467 Pfluger's cords, 356 Pharyngeal bursa, 296 membrane, 282 tonsil, 296 Pharynx, 296 Pharyngo-palatine arches, 285 Pineal body, 400 Pinna, 450 Pituitary body, 403 Placenta, 135, 140 accessory, 127 deciduate, 140 embryotrophic, 126 hsematrophic, 126 indeciduate, 140 praevia, 136 Placentar infarcts, 139 Plasmodi-trophoblast, 57, 125 Plasmodium, 125 PleurEE, 325 Pleuro-peritoneal cavity, 81, 322 Plica semilunaris, 470 Polar globules, 30 Polycaryocytes, 230 Polymastia, 152 Polyspermy, 3S\ Pons, 39S flexure, 392 INDEX 499 Post-anal gut, 283 Post-natal development, 466 Precaudal recess, 283 Precoracoid, 191 Prepuce, 368 Primitive groove, S9, 72 streak, 53, 72 Processus globularis, loi Pronephric duct, 342 Pronephros, 342 Pronuclei, 32 Prooestrum, 28 Prostate gland, 365 Prostomial mesoderm, 53, 61 Protoplasm, 2 Protovertebrae, 80 R Rathke's pouch, 287, 403 Rauber's covering layer, 48 Rectum, 283 Red nucleus, 399 Reduction of chromosomes, 15, 30 Restiform body, 395 Rete cords, 353 ovarii, 357 testis, 356 Retina, 460 Retroperitoneal lymph sac, 270 Rhinencephalon, 412 Rosenmiiller, groove of, 297 organ of, 360 Sacculus, 439 Sacral bend, 93 Salivary glands, 293 Santorini, cartilages of, 339 duct of, 31S Sarcode, i Scala tympani, 444 vestibuli, 443 Sclerotic coat, 454, 467 Sclerotome, 83 Scrotum, 368 Sebaceous glands, 149 Segmentation nucleus, 32 of ovum, 41 Semicircular ducts, 438 Semilunar valves, 240 Seminiferous tubules, 356 Septum aortic, 237 pellucidum, 411 primum, 234 secundum, 234 spurium, 234 transversum, 321, 323, 327 ventricular, 237 Sertoli cells, 14 Sex cells, 353 cords, 353 Sexual reproduction, 9 Sinusoid, 225 Sinus, coronary, 234, 260 pocularis, 359 praecervicalis, too terminalis, 224 venosus, 232 Situs inversus viscerum, 49 Skin, 143, 481 Skull, 171, 483 Socia parotidis, 293 Solitary fasciculus, 393, 419 Somatic cells, 8 Spaces of Fontana, 469 Spermatic cord, 371 Spermatid, 14 Spermatocyte, 14 Spermatogenesis, 13 Spermatogonia, 14 Spermatozoon, 11 Sphenoidal cells, 178 Spheno-palatine ganglion, 429 Spinal cord, 387, 480 nerves, 413 Spiral organ of Corti, 441 Spleen, 275, 480 Stomach, 302 Sublingual ganglion, 429 gland, 29s Submaxillary ganglion, 429 Submaxillary gland, 294 Substance islands, 223 500 INDEX Sudoriparous glands, 150 Sulcus Monroi, 399 Superfetation, 37 Suprabranchial placodes, 422 Suprarenal bodies, 374, 480 accessory, 376 Supratonsillar fossa, 297 Suture, I go Sympathetic nervous system, 423 Synchondrosis, 190 Syncytium, 125 Systems, 3 Tail filament, 96 Tarsal glands, 470 Taste, organs of, 43s Teeth, 287 Tegmentum, 398 Telencephalon, 390, 402 Testis, 354 descent of, 369 Thalami, 401 Thebesian valve, 235 Thoracic duct, 272 Thymus gland, 299, 480 Thyreoid cartilage, 338 gland, 298, 480 Thyreo-glossal duct, 298 Tissues, 3 Tongue, 291 Tonsils, 297 Touch, organs of, 433 Trachea, 337 Tragus, 450 Trophoblast, S7 Tuba auditiva, 444 Tubae uterinae, 361 Tuber cinereum, 402 Tuberculum impar, 291 Tubuli recti, 356 Tunica albuginea, 354, 356 vaginalis testis, 371 vasculosa lentis, 457 Tween-brain, 390 Twin;development, 48 Tympanic cavity, 444 membrane, 448 U Ultimo-branchial bodies, 301 Umbilical cord, 95, 119 Umbilicus, 90 Urachus, 118, 364 Ureter, 348 Urethra, 365 Urogenital sinus, 364 Uterovaginal canal, 353 Uterus, 361, 363 masculinus, 359 Utriculus, 439 prostaticus, 359 Vagina, 361, 363 Vaginal process, 369 Vallate papillae, 435 Vas deferens, 359 Veins: anterior cardinal, 256 tibial, 267 ascending lumbar, 266 azygos, 266 basilic, 267 cephalic, 266 emissary, 260 external jugular, 260 ' hemiazygos, 266 hepatic, 263 inferior vena cava, 265 innominate, 259 internal jugular, 256 jugulo-cephalic, 267 limb, 266 long saphenous, 267 portal, 262 posterior cardinal,. 256, 260 primary fibular, 267 ulnar, 266 pulmonary, 235, 267 renal, 265 INDEX SOI Veins: subcardinal, 263 superior vena cava, 259 supracardinal, 265 suprarenal, 265 umbilical, 121, 262 vitelline, 224, 261 Velum, anterior, 398 interpositum, 400 marginal, 381 posterior, 393 Vena capitis, 256 Ventricular septum, 237 Vermiform appendix, 307 Vernix caseosa, 115, 149 Vertex bend, 90 Vesicula seminalis, 359 Vieussens, annulus of, 235 Villi, chorionic, 126 intestinal, 308 Vitreous humor, 454, 465 Vulva, 368 W Wharton's jelly, 121 Winslow, foramen of, 327 Wirsung, duct of, 315 Witch milk, 153 Wolffian body, 342, 358 duct, 342, 358 ridge, 341 Wrisberg, cartilage of, 339 Yolk sac, 89, no, 115 stalk, 89, 93, no Zona pellucida, 21 Zuckerkandl, organ of, 378