wiimmmJm^tm. tk^,fH&k^^ «eHMB^!W£ikM^<^^ c-u, }4A1 !M*Uq.a3.. Cornell University Library QM 601.M19 The development of the human body; a manu 3 1924 003 122 276 Cornell University Library The original of this book is in the Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924003122276 THE DEVELOPMENT OF THE HUMAN BODY A MANUAL OF HUMAN EMBRYOLOGY J. PLAYFAIR McMURRICH, A.M., Ph.D. PROFESSOR OF ANATOMY IN THB UNIVERSITY OF MICHIGAN With T%o Hundred and Seventy Illustrations PHILADELPHIA P. BLAKISTON'S SON & CO. IOI2 WALNUT STREET ig02 Copyright, 1902, By P. BLAKISTON'S SON & CO. Press of Wm. F. Fell & Co. 1220-24 8AN8OM STREET PHILADELPHIA. PREFACE. The assimilation of the enormous mass of facts which constitute 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 re- garding 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 develop- ment, 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 understand- ing of the facts of anatomy. Naturally, the individual development claims^ the major share of attention, since its processes are the more immediate forces at work in de- termining the conditions in the adult, but where the em- bryological record fails to afford the required data, whether from its actual imperfection or from the incom- pleteness of our knowledge concerning it, recourse has been had to the facts of comparative anatomy as afford- ing indications of the historical development or evolu- tion of the parts under consideration. It has not seemed feasible to include in the book a com- IV PREFACE. plete list of the authorities consulted in its preparation. The short bibliographies appended to each chapter make no pretensions to completeness, but are merely indica- tions of some of the more important works, especially those of recent date, which consider the questions dis- cussed. For a very full bibliography of all works treating of human embryology up to 1893 reference may be made to Minot's Bibliography of Vertebrate Embryology, pub- lished in the "Memoirs of the Boston Society of Natural History," volume iv, 1893. It is fitting, however, to ac- knowledge an especial indebtedness, shared by all writers on human embryology, to the classic papers of His, chief among which is his Anato-mie menschlieher Embryonen, and grateful acknowledgments are also due to the ad- mirable text -books of Minot, O. Hertwig, and Kollmann. Anatomical Laboratory, University of Michigan. October 1, 1902. CONTENTS. PAGE. Introduction, 17-26 PART I.— GENERAL DEVELOPMENT. CHAPTER I, The Spermatozoon and Spermatogenesis; the Ovum and Its Maturation and Fertilization, 27-53 CHAPTER II. The Segmentation of the Ovum and the Formation of the Germ Layers, j 54-81 CHAPTER III. The Development of the External Form of the Human Embryo, . 82-1 1 1 CHAPTER IV. Tke Medullary Groove, Notochord, and Mesodermic Somites,. . 112-127 CHAPTER V. The Yolk-stalk, Belly-stalk, and Fetal Membranes, 128-160 PART II.— ORGANOGENY. CHAPTER VI. The Development of the Integumentary System, 161-173 CHAPTER VII. The Development of the Connective Tissues and Skeleton,. . . . 174-215 CHAPTER VIII. The Development of the Muscular System 216-239 CHAPTER IX. The Development of the Circulatory and Lymphatic Systems, . . 240-295 CHAPTER X. The Development of the Digestive Tract and Glands, 296-333 v VI CONTENTS. CHAPTER XI. page. The Development of the Pericardium and Pleuro-peritoneum, the Diaphragm and the Spleen, 334-35 1 CHAPTER XII. The Development of the Organs of Respiration, 352-359 CHAPTER XIII. The Development of the Urinogenital System and the Supra- renal Bodies, 360-393 CHAPTER XIV. The Development of the Nervous System, 394-453 CHAPTER XV. The Development of the Organs of Special Sense, 454-500 CHAPTER XVI. Post-natal Development, 501-5 18 Index, 519-527 LIST OF ILLUSTRATIONS. FIG. PAGE. 1. Ovum of New-born Child with Follicle-cells. — (Mertens), 19 2. Diagrams Illustrating the Prophases of Mitosis. — (Adapted from E. B. Wilson), 21 3. Diagrams Illustrating the Metaphase and Anphases of Mitosis. — (Adapted from E. B. Wilson), 23 4. Human Spermatozoon, 28 5. Spermatozoon of Rat, 28 6. Diagram showing Stages of Spermatogenesis as seen in Different Sectors of a Seminiferous Tubule of a Rat. — (Modified from von_ Lenhossek), 29 7. Diagram Illustrating the Reduction of the Chromosomes During Spermatogenesis, 31 8. Four Stages in the Transformation of a Spermatid into the Spermatozoon of a Rat. — (von Lenhossek), 32 9. Section through Portion of an Ovary of an Opossum (Didelphys virginiana) showing Ova and Follicles in Various Stages of Development, 34 10. Ovum from Ovary of a Woman Thirty Years of Age. — (Nagel), 35 11. Ovary of a Woman Nineteen Years of Age, Eight Days after Menstruation. — (Kollmann), 40 12. Section through the Corpus Luteum of a Rabbit, Seventy Hours post coitum. — (Sobotta) 41 13. Diagram Illustrating the Reduction of the Chromosomes during the Maturation of the Ovum, 44 14. Ovum of a Mouse showing the Maturation Spindle. — (Sobotta), 46 15. Six Stages in the Process of Fertilization of the Ovum of a Mouse.— (Sobotta), 48 16. Stages in the Segmentation of Amphioxus. — (Hatschek) 55 17. Stages in the Segmentation of Amblystoma. — (Eycleshymer) , . . 56 18. Four Stages in the Segmentation of the Blastoderm of the Chick.— (Coste), 57 19. Diagram Illustrating a Section of the Ovum of a Reptile at a Stage Corresponding to the Blastula of an Amphibian 58 20. Four Stages in the Segmentation of the Ovum of a Mouse. — (Sobotta), 60 21. Later Stages in the Segmentation of the Ovum of a Bat. — (Van Beneden), 61 22. Two Stages in the Gastrulation of Amphioxus. — (Morgan and Hazen), 65 23. Transverse Section of Amphioxus Embryo with Five Meso- dermic Pouches. — (Hatschek), 66 24. Section through a Gastrula of Amblystoma. — (Eycleshymer),. . . 67 25. Section through an Embryo Amphibian (Triton) of 2\ Days, showing the Formation of the Gastral Mesoderm.— (Hert- wig), 68 vii Vlll LIST OF ILLUSTRATIONS. FIG. PAGE. 26. longitudinal Sections through Embryos of the Gecko, showing Gastrulation.— (Will), 69 27. Diagrams Illustrating the Formation of the Gastral Mesoderm in the Gecko— (Will) 70 28. Sections of Ova of a Bat showing (A) the Formation of the ^ Endoderm and (B and C) of the Amniotic Cavity. — (Van Beneden), 72 29. A, Side View of Ovum of Rabbit Seven Days Old (Kolliker) ; B, Embryonic Disk of a Mole (Heape) ; C, Embryonic Disk of a Dog's Ovum of about Fifteen Days (Bonnet), 73 30. Posterior Portion of a Longitudinal Section through the Em- bryonic Disk of a Mole. — (After Heape), 74 31. Diagram Illustrating Concrescence. — (Duvat), 75 32. Transverse Section of the Embryonic Area of a Dog's Ovum at about the Stage of Development shown in Fig. 29, C. — (Bonnet), ; 76 33. Diagram of a Longitudinal Section through the Embryonic Disk of a Mole. — (Heape) 77 34. Transverse Section through the Embryonic Disk of a Rabbit. — (After Van Beneden) 78 35. Section of Embryo and Adjacent Portion of an Ovum of 1 mm. —(Peters), 82 36. Diagrams to show the Probable Relationships of the Parts in the Embryos Represented in Figs. 28, C, and 35, 83 37. Ovum Measuring 6 X 4.5 mm. The Left Half of the Chorion has Been Removed to show the Embryo. — (von Spee), .... 85 38. Embryo 1.54 mm. in Length, from the Dorsal Surface.— (von Spee), 85 39. Diagrams Illustrating the Constriction of the Embryo from the Yolk-sac, 86 40. Embryo 2.5 mm. Long. — (Allen Thomson), 87 41. Reconstruction of Embryo 2.11 mm. Long. — (After Eternod),. . 88 42. Embryo 2.5 mm. Long. — (Kallmann), 89 43. Embryo Lg, 2.15 mm. Long. — (His), 90 44. Floor of the Pharynx of Embryo B, 7 mm. Long. — (His), .... 92 45. Embryo Lr, 4.2 mm. Long. — (His), 93 46. Embryo of from Twenty to Twenty-five Days. — (Coste), 95 47. Embryo 9.1 mm. Long. — (His), 96 48. Embryo Br 2 , 13.6 mm. Long. — (His), 98 49. A, Embryo S 2 , 15 mm. Long (snowing Ectopia of the Heart); B, Embryo L s , 17.5 mm. Long. — (His), 99 50. Embryo Wt, 23 mm. Long.— (His), 100 51. Head of Embryo of 6.9 mm. — (His), 102 52. Face of Embryo of 8 mm. — (His), 103 53. Face of Embryo after the Completion of the Upper Jaw. — (His), 104 54. Embryo 1.34 mm. Long. — (Eternod), 113 ' 55. Diagram of a Longitudinal Section through an Embryo of 1.54 mm. — (von Spee), 114 56. Diagrams showing the Manner of the Closure of the Medullary Groove, 115 57. Transverse Sections through Mole Embryos, showing the Formation of the Notochord. — (Heape), 116 58. Transverse Section through the Second Mesodermic Somite of a Sheep Embryo 3 mm. Long. — (Bonnet), 118 LIST OF ILLUSTRATIONS. IX FIG. PAGE. 59. Transverse Section of an Embryo of 2.5 mm. (See Fig. 42) showing on either side of the Medullary Canal a Mesodermic Somite, the Intermediate Cell-mass, and the Ventral Meso- derm. — {von Lenhossek), 1 19 60. Transverse Section of an Embryo of 4.25 mm. at the Level of the Arm Rudiment. — {Kollmann), 121 61. Diagrams Illustrating the History of the Gastral Mesoderm. — {Modified from Kollmann), 125 62. Diagrams Illustrating the Formation of the Amnion and Allantois in the Chick. — {Gegenbaur), 129 63. Diagrams Illustrating the Formation of the Umbilical Cord,. . 132 64. Transverse Section through the Belly-stalk of an Embryo of 2.15 mm.— {His), 137 65. Transverse Sections of the Umbilical Cord of Embryos of {A) 1.8 cm. and {B) 25 cm 140 66. Two Diagrams Illustrating the Formation of Chorionic Villi. — {Peters), 142 67. Two Villi from the Chorion of an Embryo of 7 mm., 143 68. Transverse Sections through Chorionic Villi in {A) the Fifth and {B) the Seventh Month of Development. — {A, which is more highly magnified than B, from Szymonowicz; B from Minot), 144 69. Mature Placenta after Separation from the Uterus. — {Koll- mann), 146 70. Section through the Placental Chorion of an Embryo of Seven Months.— {Minot), 147 71. Diagram showing the Relations of the Fetal Membranes, 148 72. Surface View of Half of the Decidua Vera at the End of the Third Week of Gestation. — {Kollmann) 149 73. Diagrammatic Sections of the Uterine Mucosa, A, in the Non- pregnant Uterus, and B, at the Beginning of Pregnancy. — {Kundrat and Engelmann), 150 74. Section of an Ovum of 1 mm. A Section of the Embryo Lies in the Lower Part of the Cavity of the Ovum. — {From Strahl, after Peters), 152 75. Section through a Placenta of Seven Months' Development. — {Minot), 154 76. Diagrammatic Section through the Human Placenta at the Middle of the Fifth Month. — {From Hertwig, after Leopold), Colored, 157 77. 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. 162 78. Diagram showing the Cutaneous Distribution of the Spinal Nerves. — {Head), ; 163 79. Diagram showing the Overlap of the III, IV, and V Intercostal Nerves of a Monkey. — {Sherrington), 164 80. Longitudinal Section through the Terminal Joint of the Index- finger of an Embryo of 4.5 cm., 165 81. Longitudinal Section through the Nail Area in an Embryo of 17 cm. — {Okamura), 166 82. The Development of a Hair. — {Kollmann), 167 83. Lower Surface of a Detached Portion of Epidermis from the Dorsum of the Hand. — {Blaschko), 169 84. Milk Ridge {mr) in a Human Embryo. — {Kallius), 170 X LIST OF ILLUSTRATIONS. FIG. PAGE. 85. Sections through the Epidermal Thickenings which Represent the Mammary Gland in Embryos (A) of 6 cm. and (B) of 10.2 cm., 171 86. Section through the Mammary Gland of an Embryo of 25 cm. — {From Nagel, after Basch), 172 87. Portion of the Center of Ossification of the Parietal Bone of a Human Embryo, 175 88. Longitudinal Section of Phalanx of a Finger of an Embryo of 3 i Months. — (Szymonowicz), 176 89. The Ossification Center of Fig. 88 More Highly Magnified — (Szymonowicz) , 177 90. The Ossification Centers of the Femur.— (Testut), 179 91. 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. — (After Flourens), 180 92. Transverse Section through the Intervertebral Plate of the First Cervical Vertebra of a Calf Embryo of 8.8 mm. — (Froriep), 181 93. Longitudinal Section through the Occipital Region and Upper Cervical Vertebrae of a Calf Embryo of 18.5 mm. — (Froriep), 182 94. A, A Vertebra at Birth; B, Lumbar Vertebra showing Secondary Centers of Ossification. — (Sappey) 186 95. A, Upper Surface of the First Sacral Veretbra, and B, Ventral View of the Sacrum showing Primary Centers of Ossifica- tion. — (Sappey), 187 96. Formation of the Sternum in an Embryo of about 3 cm. — (Ruge), 189 97. Sternum of New-born Child, showing Centers of Ossification. — (Gegenbaur), 190 98. Reconstruction of the Chondrocranium of an Embryo of 14 mm. —(Levi), 191 99. Frontal Section through the Occipital and Upper Cervical Regions of a Calf Embryo of 8.7 mm. — (Froriep) 193 100. Diagram showing the Five Branchial Cartilages, I to V, 194 101. Occipital Bone of a Fetus at Term, 196 102. Sphenoid Bone from Embryo of 3£ to 4 Months. — (Sappey),. . 197 103. Anterior Portion of the Base of the Skull of a 6 to 7 Months' Embryo. — (After von Spee), 198 104. The Temporal Bone at Birth. The Styloid Process and Audi- tory Ossicles are not Represented. — (Poirier), 200 105. Diagram of the Ossifications of which the Maxilla is Composed, as seen from the Outer Surface. The Arrow Passes through the Infraorbital Canal. — (From von Spee, after Sappey) ..... 203 106. Diagram showing the Categories to which the Bones of the Skull Belong, 205 107. The Ossification Centers of the Scapula.— (Testut), 207 108. Reconstruction of an Embryonic Carpus, 209 109. The Ossification Centers of the Os Innominatum. — (Testut),. . 210 110. Longitudinal Section through the Joint of the Great Toe in an Embryo of 4.5 cm. — (Nicolas) 213 111. Cross-sections of Heart-muscle Cells from Pig Embryos of (A) 10 mm. and (B and Q 20 mm. — (Macallum), 217 112. Cross-section of a Muscle from the Thigh of a Pig Embryo 75 mm. Long. — (Macallum) 218 LIST OF ILLUSTRATIONS. XI FIG. PAGE. 113. Embryo of 13 mm. showing the Formation of the Rectus Muscle.— {Malt), 223 114. Perineal Region of Embryos of (A) Two Months and (B) Four to Five Months, showing the Development of the Perineal Muscles. — (Popowsky), 227 115. Head of Embryos (A) of Two Months and (B) of Three Months showing the Extension of the Seventh Nerve upon the Face. — (Popowsky), 230 116. Diagram of a Segment of the Body and Limb. — (Kollmann),. . 234 117. External Surface of the Os Innominatum showing the Attach- ment of Muscles and the Zones Supplied by the Various Nerves.— (Bolk), 235 118. Sections through (A) the Thigh and (B) the Calf showing the Zones Supplied by the Nerves. The Nerves are Numbered in Continuation with the Thoracic Series. — (A after Bolk), . . 236 119. Section through the Upper Part of the Arm showing the Zones Supplied by the Nerves. — (Bolk), 237 120. Transverse Section through the Area Vasculosa of Rabbit Em- bryos showing the Transformation of Mesoderm Cells into the Vascular Cords. — (van der Stricht), 241 121. Surface View of a Portion of the Area Vasculosa of a Chick. — (Disse), 242 122. The Vascular Areas of Rabbit Embryos. In B the Veins are Represented by Black and the Network is Omitted. — ("van Beneden and Julin) 243 123. Section of a Portion of the Liver of a Rabbit Embryo of 5 mm. — (van der Stricht), 245 124. Stages in the Transformation of an Erythrocyte into an Erythro- plastid. — (van der Stricht), 245 125. Portion of a Section from the Liver of an Embryo Cat of 2.7 mm. showing a Megacaryocyte Surrounded by Erythrocytes in a Blood-vessel. — (Howell), 247 126. Diagrams Illustrating the Formation of the Heart in the Guinea- pig. — (After Strahl and Carius), 249 127. Heart of Embryo of 2.15 mm., from a Reconstruction. — (His), 250 128. Heart of Embryo of 4.2 mm. seen from the Dorsal Surface. — (His), 250 129. Heart of Embryo of 5 mm., seen from in Front and Slightly from Above.— (His), 251 130. Inner Surface of the Heart of an Embryo of 10 mm. — (His), . . 252 131. Heart of Embryo of 10.2 cm. from which Half of the Right Auricle has Been Removed, 253 132. Section through a Reconstruction of the Heart of a Rabbit Em- bryo of 10.1 mm. — (Bom), 255 133. Diagrams of Sections through the Heart of Embryo Rabbits to show the Mode of Division of the Ventricles and of the Auriculo-ventricular Orifice, 257 134. Diagrams showing the Development of the Auriculo-ventricular Valves. — (From Hertwig, after Gegenbaur) , 258 135. Diagrams Illustrating the Formation of the Semilunar Valves. — (Gegenbaur), 259 136. Reconstruction of Embryo of 2.6 mm. — (His), . . .^ 261 137. Diagram Illustrating the Arrangement of the Branchial Vessels, 262 138. Arterial System of an Embryo of 10 mm. — (His) 264 Xll LIST OF ILLUSTRATIONS. FIG. PAGE. 139. Diagram Illustrating the Changes in the Arrangement of the Branchial Arch Vessels, 265 140. Diagram showing the Relations of the Lateral Branches to the Aortic Arches, 266 141. Diagram Illustrating the Development of the Umbilical Arteries, 267 142. The Development of the Vertebral Artery in a Rabbit Embryo of Twelve Days. — (Hochstetter), 269 143. Embryo of 13 mm. showing the Mode of Development of the Internal Mammary and Deep Epigastric Arteries. — (Malt), . 270 144. Diagrams showing an Early and a Late Stage in the Develop- ment of the Arteries of the Arm, 273 145. Diagrams Illustrating Stages in the Development of the Arteries of the Leg, 275 146. Reconstruction of the Head Veins of Guinea-pig Embryos. — (Salzer), 278 147. Diagrams showing the Development of the Superior Vena Cava, 279 148. Diagrams Illustrating the Transformations of the Omphalo- mesenteric and Umbilical Veins. — (Hochstetter), 282 149. A, The Venous Trunks of an Embryo of 5 mm. seen from the Ventral Surface; B, Diagram Illustrating the Transforma- tion to the Adult Condition. — (His), 283 150. Diagrams Illustrating the Development of the Inferior Vena Cava, 285 151. The Development of the Arm Veins in the Rabbit. — (Hoch- stetter) 287 152. The Fetal Circulation. — (From Kallmann), Colored, 289 153. Diagrams showing the Arrangement of the Lymphatic Vessels in Pig Embryos of (A) 20 mm. and (B) 40 mm. — (Sabin), . . 292 154. Developing Lymphatic Gland from the Axilla of an Embryo of Eleven Weeks.— (Chiemtz), 293 155. Reconstruction of the Anterior Portion of an Embryo of 2.15 mm.— (His), 297 156. Reconstruction of the Hind End of an Embryo 6.5 mm. Long. — (Keibel), 298 157. View of the Roof of the Oral Fossa of Embryo showing the Lip- groove and the Formation of the Palate. — (His), 299 158. Transverse Sections through the Lower Jaw showing the Forma- tion of the Dental Shelf in Embryos of (^4) 17 mm. and (B) 40 mm.— (Rose), 301 159. Section through the Frst Molar Tooth of a Rat, Twelve Days Old. — (von Brunn), 303 160. Floor of the Pharynx of Embryos of (A) 7 and (B) 10 mm. showing the Development of the Tongue. — (His) 306 161. The Floor of the Pharynx of an Embryo of about 20 mm. — (His), 307 162. Diagram of the Distribution of the Sensory Nerves of the Tongue. — (Zander) 308 163. An Oblique Section through the Mouth Cavity of an Embryo of about 16 to 17 mm. — (His), 309 164. The Floor of the Pharynx of an Embryo of 2.15 mm. — (His),. . 311 165. Reconstructions of the Branchial Epithelial Bodies of Embryos of (A) 14 mm. and (B) 26 mm. — (Tourneux and Verdun),. . 313 166. Thyreoid, Thymus and Epithelial Bodies of a New-born Child. — (Groschuff) , 315 167. Diagram showing the Origin of the Various Branchial Epi- thelial Bodies. — (Kohn), 316 LIST OF ILLUSTRATIONS. Xlll FIG. PAGE. 168. Reconstructions of the Digestive Tract of Embryos of (A) 4.2 mm. and (B) 5 mm. — (His), 318 169. Reconstruction of Embryo of 20 mm. — (Mall) 320 170. Reconstruction of the Intestine of an Embryo of 19 mm. The Figures on the Intestine Indicate the Primary Coils. — (Mall), 321 171. Representation of the Coilings of the Intestine in the Adult Condition. The Numbers indicate the Primary Coils. — (Malt) 322 172. Caecum of Embryo of 10.2 cm., 323 173. Reconstruction of a Portion of the Intestine of an Embryo of 28 mm., showing the Longitudinal Folds from which the Villi are Formed. — (Berry), 324 174. Reconstructions of the Liver Outgrowths of Rabbit Embryos of (A) 5 mm. and (B) of 8 mm. — (Hammar), 326 175. Transverse Section through the Liver of an Embryo of Four Months. — (Toldt and Zuckerkandl) 327 176. Transverse Sections of Portions of the Liver of (4) a Fetus of Six Months and (B) a Child of Four Years. — Toldt and Zuckerkandl), 328 177. Injected Bile Capillaries of Pig Embryos of (A) 8 cm., (B) 16 cm., and (Q of Adult Pig. — (Hendrickson), 329 178. Reconstruction of the Pancreatic Outgrowths of an Embryo of 7.5 mm.— (Helly), 331 179. Reconstruction of a Rabbit Embryo of Eight Days, with the Pericardial Cavity Laid Open. — (His), 335 180. Transverse Sections of a Rabbit Embryo showing the Division of the Parietal Recesses by the Omphalo-mesenteric Veins. — (Ravn), 336 181. Reconstruction from a Rabbit Embryo of Nine Days showing the Septum Transversum from Above. — (Ravn), 337 182. Diagrams of (A) a Sagittal Section of an Embryo showing the Liver Enclosed within the Septum Transversum; (B) a Frontal Section of the Same; (Q a Frontal Section of a Eater Stage when the Liver has Separated from the Dia- phragm, 339 183. Diagram showing the Position of the Diaphragm in Embryos of Different Ages.— (Malt) , 342 184. Diagram showing the Arrangement of the Mesentery and Visceral Branches of the Abdominal Aorta in an Embryo of Six Weeks.— (Toldt) 344 185. Diagrams Illustrating the Development of the Great Omentum and the Transverse Mesocolon. — (Hertwig), 345 186. Diagrams Illustrating the Manner in which the Fixation of the Descending Colon (C) takes Place, 346 187. Diagrams showing the Development of the Great Omentum and its Fusion with the Transverse Mesocolon. — (After Allen Thomson), 348 188. Section through the Left Layer of the Mesogastrium of a Chick Embryo of Ninety-three Hours, showing the Origin of the .Spleen.— (Tonkoff), 350 189. Portion of a Section through an Embryo of the Fourth Week. — (Toldt), 352 190. Reconstruction of the Lung Outgrowths of Embryos of (A) 10, (B) 8.5, and (C) 10.5 mm.— (His), 353 XIV LIST OF ILLUSTRATIONS. FIG. PAGE. 191. Diagram of the Final Branches of the Mammalian Bronchi. — {Miller), 355 192. Reconstruction of the Opening into the Larynx in an Embryo of Twenty-eight Days, Seen from Behind and Above, the Dorsal Wall of the Pharynx Being Cut Away. — (Kallius),. . 356 193. Reconstruction of the Mesenchyme Condensations which Represent the Hyoid and Thyreoid Cartilages in an Em- bryo of Forty Days. — (Kaliius), 357 194. Transverse Section through the Abdominal Region of a Rabbit Embryo of 12 mm. — (Mihalkovicz), 360 195. Transverse Section through Chick Embryo of about Thirty-six Hours, 362 196. Transverse Section of the Wolffian Ridge of a Chick Embryo of Three Days. — (Mihalkovicz), 364 197. Urinogenital Apparatus of a Male Pig Embryo of 6 cm. — (Mihalkovicz), 365 198. Diagrams of Early Stages in the Development of the Meta- nephric Tubules. — (Haycraft), 367 199. Three Stages in the Development of a Uriniferous Tubule of a Rabbit. — (Haycrafi), 368 200. Transverse Section through the Abdominal Region of an Em- bryo of 25 mm. — (Keibel), 370 201. Reproductive Organs of a Female Embryo of Six Months. — (Adapted from Mihalkovicz), 372 202. Section through the Testis and the Broad Ligament of the Testis of an Embryo of 5.5 mm. — (Mihalkovicz), 373 203. Diagram of an Epithelial Invagination of the Ovary of a Rabbit. — (von Winiwarter), '. 375 204. Section of the Ovary of a New-born Child. — (From Gegenbaur, after Waldeyer), 375 205. Diagrams Illustrating the Transformations of the Mflllerian and Wolffian Ducts. — (Modified from Huxley), . . . .Colored, 378 206. Reconstruction of the Cloacal Region of an Embryo of 14 mm. — (Keibel), 382 207. Reconstruction of the Cloacal Structures of an Embryo of 25 mm. — (Adapted from Keibel), 383 208. The External Genitalia of an Embryo of 25 mm. — (Keibel) 385 209. Diagrams Illustrating the Descent of the Testis. — (After Hertwig), 389 210. Section through a Portion of the Wolffian Ridge of a Rabbit Embryo of 6.5 mm. — (Aichet), 391 211. Ependymal Cells from the Spinal Cord of an Embryo of 4.25 mm. — (His) 395 212. Diagrams showing the Development of the Mantle Layer in the Spinal Cord. — (Schaper), 396 213. Three Sections through the Medullary Canal of an Embryo of 2.5 mm. — (von Lenhossek), " 397 214. Cells from the Gasserian Ganglian of a Guinea-pig Embryo. — (van Gehuchten), 398 215. Transverse Sections through the Spinal Cords of Embryos of (A) about Four and a Half Weeks and (B) about Three Months. — (His), 402 216. Reconstruction of the Brain of an Embryo of 2.15 mm. — (His), 404 217. Median Longitudinal Section of the Brain of an Embryo of the Third Month.— (His), 406 LIST OF ILLUSTRATIONS. XV FIG. PAGE. 218. Transverse Section through the Medulla Oblongata of an Em- bryo of 9. 1 mm. — (.His), 408 219. Transverse Section through the Medulla Oblongata of an Em- bryo of about Eight Weeks. — (His), 409 220. A, Dorsal View of the Brain of a Rabbit Embryo of 16 mm.; B, Median Longitudinal Section of a Calf Embryo of 3 cm. — (Mihalkovicz), 41 1 221. Diagram Representing the Differentiation of the Cerebellar Cells.— (Schaper), 412 222. Transverse Section of the Thalamencephalon of an Embryo of Five Weeks.— (His), 415 223. Dorsal View of the Brain, the Roof of the Lateral Ventricles being Removed, of an Embryo of 13.6 mm. — (His) 417 224. Median Longitudinal Section of the Brain of an Embryo of 13.6 mm.— (His), 419 225. Median Longitudinal Section of the Brain of an Embryo Calf of 5 cm. — (Mihalkovicz) , 42 1 226. Brain of an Embryo of the Fourth Month, 423 227. Cereberal Hemisphere of an Embryo of about the Seventh Month. — (Cunningham), 425 228. Median Longitudinal Section of the Brain of an Embryo of Three Months. — (Mihalkovicz), 426 229. Median Longitudinal Section of the Brain of an Embryo of the Fifth Month.— (Mihalkovicz), 427 230. Transverse Section through the Medulla Oblongata of an Em- bryo of 10 mm., showing the Nuclei of Origin of the Vagus (X) and Hypoglossal (XII) Nerves.— (His), 432 23 1. Diagram showing the Sensory Components of the Cranial Nerves of a Fish (Menidia). — (Herrick) 436 232. Transverse Section through an Embryo Shark (Scyllium) of 15 mm., showing the Origin of a Sympathetic Ganglion. — (Onodi) 442 233. Diagram snowing the Arrangement of the Neurones of the Sympathetic System. — (Adapted from Huber), . . . .Colored, 443 234. Transverse Section through the Spinal Card of an Embryo of 7 mm.— (His), . . . : 445 235. Reconstruction of the Sympathetic System of an Embrvo of 10.2 mm.— (His, Jr.), 447 236. Section of a Cell Ball from the Intercarotid Ganglion of Man. — (From Bohm and Davidoff, after Schaper) 449 237. Accessory Sympathetic Organs of Zuckerkandl from a New- born Child. — (ZuckerkandF) , 451 238. Diagram Illustrating the Relations of the Fibers of the Olfactory Nerve. — ( Van Gehuchten), 456 239. Diagrams Representing the Development of a Circumvallate Papilla.— (Graberg), 458 240. Transverse Section Passing through the Otocyst (ot) of Em- bryos of (A) 2.4 mm. and (B) 4 mm.— (His), 460 241. Reconstructions of the Otocysts of Embryos of (A) 6.9 mm. and (B) 10.2 mm.— (His, Jr.), .' 461 242. Reconstruction of the Otocyst of an Embryo of 13.5 mm. — (His, Jr.), 462 243. Reconstruction of the Otocvst of an Embryo of 22 mm. — (His, Jr.), i 463 XVI LIST OF ILLUSTRATIONS. FIG. PAGE. 244. The Right Internal Ear of an Embryo of Six Months.— (Relzius) , 465 245. Section of the Scala Media of the Cochlea of a Rabbit Embryo of 55 mm. — (Baginsky), . . 466 246. Transverse Section through a Semicircular Canal of a Rabbit Embryo of Twenty-four Days. — ( Von Kolliker), 467 247. Diagrammatic Transverse Section through a Coil of the Cochlea, showing the Relations of the Scalae. — (From Gerlach),. . . . 468 248. Semi-diagrammatic View of the Auditory Ossicles of an Em- bryo of Six Weeks. — (Siebenmann) , . 470 249. Diagrams Illustrating the Mode of Extension of the Tympanic Cavity Around the Auditory Ossicles, 47 1 250. Horizontal Section Passing through the Dorsal Wall of the External Auditory Meatus in an Embryo of 4.5 cm. — (Siebenmann) , 473 251. Stages in the Development of the Pinna. — (His), 475 252. Early Stage in the Development of the Lens in a Rabbit Em- bryo.— (Rabt), ; 477 253. Reconstruction of the Brain of an Embryo of Four Weeks, showing the Chorioid Fissure. — (His) 478 254. Horizontal Section through the Eye of an Embryo Pig of 7 mm., 479 255. Sections through the Lens (A) of Human Embryo of Thirty to Thirty-one Days and (B) of Pig Embryo of 36 mm. — (Rabt), 481 256. Posterior (Inner) Surface of the Lens from an Adult showing the Sutural Lines.— (Rabt), 482 257. Radial Section through the Iris of an Embryo of 19 cm. — (Szili), 485 258. Portion of a Transverse Section of the Retina of a New-born Rabbit.— (Falchi), 487 259. Diagram showing the Development of the Retinal Elements. — (Kattius, after Cajat), 488 260. Diagrammatic Longitudinal Section of the Optic Cup and Stalk passing through the Chorioid Fissure, 490 261. Transverse Sections through the Proximal Part of the Optic Stalk of Rat Embryos of (A) 9 mm. and (B) 11 mm. — (Robinson), 491 262. Reconstruction of a. Portion of the Eye of an Embryo of 13.8 mm. — (ffii), 493 263. Transverse Section through the Ciliary Region of a Chick Em- bryo of Sixteen Days. — (Angelucci), 494 264. Transverse Section through the Ciliary Region of a Pig Em- bryo of 23 mm. — (Angelucci), 496 265. Section through the Margins of the Fused Eyelids in an Em- bryo of Six Months. — (Schweigger-Seidl), 498 266. Child and Man Drawn to the Same Scale. — (Langer, from the "Growth of the Brain," Contemporary Science Series, by permission of Charles Scribner's Sons), 502 267. Curves showing the Annual Increase in Weight in (I) Boys and (II) Girls. — (Stephenson), 506 268. Longitudinal Section through the Sacrum of a New-born Female Child. — (Fehling), 509 269. Skin of a New-born Child and of an Adult Man, Drawn to Approximately the Same Scale. — (Henke), 512 270. Longitudinal Sections of the Head of the Femur of (A) New- born Child and (B) a Later Stage of Development. — (Henke), 517 THE DEVELOPMENT OF THE HUMAN BODY INTRODUCTION. A little more than sixty years ago (1839) one of the fundamental principles of biology was established by Schleiden and Schwann as the cell theory. According to this, all organisms are composed of one or more structural units termed cells, each of which, in multicellular organ- isms, maintains an individual existence and yet contri- butes with its fellows to the general existence of the in- dividual. Viewed in the light of this theory, the human body is a community, an aggregate of many individual units, each of which leads to a certain extent an inde- pendent 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 indica- tions of a definite limiting membrane had been noted, and in 1835 a French naturalist, Dujardin, had described 2 17 1 8 THE DEVELOPMENT OF THE HUMAN BODY. the gelatinous material of which certain marine organ- isms (Rhizopoda) were composed, terming it sarcode and maintaining it to be the material substratum which conditioned the various vital phenomena exhibited by the organisms. Later, in 1846, a botanist, von Mohl, observed that living plant cells contained a similar sub- stance, upon which he believed the existence of the cell as a vital structure was dependent, and he bestowed upon this substance the name protoplasm, by which it is now universally known. By these discoveries the importance originally attrib- uted to the cell- wall was greatly lessened and in 1864 Max Schultze reformulated the cell theory, defining the cell as a mass of protoplasm, the presence or absence of a limiting membrane or cell- wall being immaterial. 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. But all these cells are not alike, 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 performance of another duty, so too, in the body, * 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. 19 one group of cells takes upon itself one especial function and another another. There is, in other words, in the cell-community a physiological division of labor. Indeed, the comparison of the cell-community to the social community may be carried still further, for just as grada- tions of individuality may be recognized in the individual, the municipality, the state, and the republic, so too in the cell-community there are cells ; tissues, each of which is an aggregate of similar cells; organs, which are aggre- gates of tissues, one, however, predominating and deter- mining the character of the organ; and systems, which are aggregates of organs having correlated functions. It is the province of embry- ology to study the mode of di- vision of the fertilized ovum and the progressive differenti- ation of the resulting cells to form the tissues, organs, and systems. But before consider- ing 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 (Fig. 1), as has been already stated, is a mass of protoplasm, a substance which in the living condition is a viscous fluid resembling in many of its peculiarities egg- albumen, and like this being coagulated when heated or when exposed to the action of various chemical reagents. As to the structure of living protoplasm little is yet known, since the application of the reagents necessary for its accu- rate study and analysis results in its disintegration or coagulation. But even in the living cell it can be seen that the protoplasm is not a simple homogeneous substance. What is termed a nucleus is usually clearly Fig. 1. — Ovum of New-born Child with Follicle- cells. — (Mertens.) 2d THE DEVELOPMENT OF THE HUMAN BODY. discernible as a more or less spherical body of a greater refractive index than the surrounding protoplasm, and since this is a permanent organ of the cell it is con- venient to distinguish the surrounding protoplasm as the cytoplasm from the nuclear protoplasm or karyoplasm. The study of protoplasm coagulated by reagents seems to indicate that it is a mixture of substances rather than a simple chemical compound. Both the cytoplasm and the karyoplasm consist of a more solid substance, the reticulum, which forms a network or felt-work, in the interstices of which is a more fluid material, the enchy- lema* The karyoplasm, in addition, has scattered along the fibers of its reticulum a peculiar material termed chromatin and usually contains embedded in its substance one or more spherical bodies termed nucleoli, which may be simply larger masses of chromatin or bodies of special chemical composition. And, finally, in all actively growing cells there is differentiated in the cytoplasm a peculiar body known as the archoplasm sphere in the center of which there is usually a minute spherical body termed the centrosome. It has been already stated that new cells arise by the division of preexisting ones, and this process is associated with a series of complicated 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 * It has been observed that certain coagulable substances and gelatin, when subjected to the reagents usually employed for "fixing" proto- plasm, present a structure similar to that of protoplasm, and it has been held that protoplasm in the uncoagulated condition is, like these sub- stances, a more or less homogeneous material. On the other hand, Biitschli maintains that living protoplasm has a foam-structure and is, in other words, an emulsion. INTRODUCTION. 21 themselves so as to form fibrils radiating in all directions from the sphere as a center, and the archoplasm with its contained centrosome gradually elongates and finally divides, each portion retaining its share of the radiating fibrils, so that two asters, as the aggregate of centrosome, Fig. 2. — Diagrams Illustrating the Prophases op Mitosis. — {Adapted from E. B. Wilson.) 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 im- 22 THE DEVELOPMENT OF THE HUMAN BODY. portant changes have been taking place in the mean time. The chromatin, originally scattered irregularly along the reticulum, has gradually aggregated to form a continu- ous 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. Thus, in the mouse, the salaman- der, and the trout the number of chromosomes is twenty- four; in the ox, the guinea-pig, and man it is sixteen; while in one of the round- worms {Ascaris) the number may be as small as four, or even two. It is to be noted that the number is always an even one. 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 chromosomes 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. The next stage, the metaphase (Fig. 3, A), consists of the division, 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 com- pleted the anaphases are inaugurated by the halves of each chromosome separating from one another and ap- proaching one of the asters (Fig. 3, B), and a group of chromosomes, containing half of 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 reticu- lum and the chromosomes of each group become irregular INTRODUCTION. 23 in shape and gradually spread out upon the nuclear reticulum so that two nuclei, each similar to the one from which the process started, are formed (Fig. 3, D). Before all these changes are accomplished, however, a Fig. 3. — Diagrams Illustrating the Metaphase and Anphases op Mitosis. — (Adapted from E. B. Wilson.) constriction makes its appearance at the surface of the cytoplasm (Fig. 3, C) and, gradually deepening, divides the cytoplasm in a plane passing through the equator of the amphiaster and gives rise to two separate cells (Fig. 3-D)- 24 THE DEVELOPMENT OF THE HUMAN BODY. This complicated process, which is known as karyo- kinesis or mitosis, is the one usually observed in dividing cells, but occasionally a cell divides by the nucleus be- coming constricted and dividing 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 it seems probable that it occurs, as a rule, only in cells whose reproductive activities are becoming impaired. In actively reproducing cells the mitotic method of divi- sion may. be regarded as the rule. Since the process of development consists of the multi- plication of a single original cell and the differentiation of the cell aggregate so formed, it follows that the starting- point of each line of individual development is to be found in a cell which forms part of an individual of the preceding generation. In other words, each individual represents one generation in esse and the succeeding gen- eration 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 ag- gregate of cells, which, by the physiological division of labor, specialize themselves for various functions. 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 neces- sary for the maintenance 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: INTRODUCTION. 25 First generation Somatic cells -f- germ cells Second generation Somatic cells -f- germ cells 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 differen- tiated anew for each generation from the germ cells, the latter, which may be termed collectively the germ-plasm, are handed on from generation to generation without interruption, and it may be supposed that this has been the case ab initio. This is the doctrine of the continuity of the germ-plasm, 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 pro- duced 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 accom- plished by a division 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 number of forms (e.g ., bees, Phylloxera, water-fleas) the germ cells are able to undergo development without previously being fertilized, this constituting a method of reproduction known as parthenogenesis. But in all these cases sexual reproduction also occurs, and in all the more highly organ- ized animals it is the only method which normally occurs ; 26 THE DEVELOPMENT OF THE HUMAN BODY. 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 different 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 nutrition and 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 individual, but in all the verte- brates (with rare exceptions in some of the lower orders) each individual produces only ova or spermatozoa, or, as it is generally stated, the sexes are distinct. It is of importance, then, that the peculiarities of the two forms of germ cells, as they occur in the human species, should be considered. LITERATURE. E. B. Wilson: "The Cell in Development and Inheritance." Third edition. New York, 1900. O. HerTwig: "Die Zelle und die Gewebe." Jena, 1893. PART I. GENERAL DEVELOPMENT. CHAPTER I. THE SPERMATOZOON AND SPERMATOGEN- ESIS; THE OVUM AND ITS MATURATION AND FERTILIZATION. The Spermatozoon. — The human spermatozoon (Fig. 4) is a minute and greatly elongated cell, measuring about 0.05 mm. in length and consisting of an anterior broader portion or head (k) and a narrow thread-like tail (/). The head measures about 0.005 mm. in length and when viewed from one surface (Fig. 4, A) 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, B). The tail consists of several portions. Situated immediately behind the head is a short cylindrical portion measuring 0.006 mm. in length which is termed the middle-piece or neck (m), and behind this is the flagellum, of about the same diameter as the middle-piece but forming about four-fifths (0.04 mm.) of the entire length of the spermatozoon. The axis of the flagellum is formed by a delicate filament which projects somewhat beyond the flagellum, forming what is termed the terminal filament or end-piece (e). In addition to these various parts, the spermatozoa of many mammalia possess a head-cap (Fig. 5, he) covering the anterior 27 28 THE DEVELOPMENT OF THE HUMAN BODY. end of the head and a spiral membrane wound around the flagellum. The presence of these structures has not yet been generally observed in the human spermatozoon, though several observers have claimed the existence of a spiral membrane, V Fig. 4. — Human Spermatozoon. 1, Front view, 2, side view of the head; e, terminal filament; k, head; /, tail; w, middle-piece. {After Retzius.) Fig. 5. — Spermatozoon op Rat. h, Head; he, head-cap; mp, mid- dle-piece; n, neck. — {Jensen.) and the head-cap undoubtedly exists in the earlier stages of the development of the spermatozoon, though it may later be lost. To understand the significance of the various parts entering into the composition of the spermatozoon a study of their development is necessary, and since the various processes of spermatogenesis have been much more accurately observed in such mammalia as the rat SPERMATOGENESIS. 2 9 and guinea-pig than in man, the description which fol- lows will be based on what has been described as occur- ring in these forms. From what is known of the sperma- togenesis in man it 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 Fig. 6. — Diagram showing Stages op Spermatogenesis as seen in Different Sectors of a Seminiferous Tubule of a Rat. s, Sertoli cell; sc 1 , spermatocyte of the first order; sc 2 , spermatocyte of • the second order; sg, spermatogone; sp, spermatid; sz, spermato- zoon — (Modified from von Lenhossek.) all be seen at any one part of a tubule, but the formation of the spermatozoa seems to pass along each tubule in a wave-like manner and the appearances presented at different points of the wave may be represented diagram- matically as in Fig. 6. In the first section of this figure four different genera- tions of cells are represented; above are mature sperma- tozoa lying in the lumen of the tubule, while next the 30 THE DEVELOPMENT OF THE HUMAN BODY. 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 larger one (s) will develop into a structure known as a Sertoli cell, while the others are parent cells of spermatozoa and are termed spermatogonia (sg). In the next section the Ser- toli cell is seen to have become considerably enlarged, its cytoplasm projecting toward the lumen of the tu- bule, and in the third section the enlargement has increased to such an extent that the spermatogonia are forced away from the basement membrane, with which the Sertoli cell alone is in contact. In the fourth section the spermatogonia are seen in process of division; one of the cells so formed will persist as a spermatogone, while the other forms what is termed a primary spermatocyte (sc 1 ). The results of the division are seen in the last section, where four spermatogonia are seen again in contact with the basement membrane and above them are four primary spermatocytes. Re- turning now to the first and second sections, the layer of primary spermatocytes may still be seen, indications of an approaching division being furnished by the ar- rangement of the chromatin in those of the second sec- tion, and in the third section the division is seen in pro- gress, the two cells which result from it being termed secondary spermatocytes (sc 2 ). These cells almost im- mediately undergo division, as shown in the fourth sec- tion, each giving rise to two spermatids (sp), each of which becomes later on directly transformed into a sper- matozoon (sz). From the primary spermatocyte there have been formed, therefore, as the result of two mi- toses, four cells, each of which represents a spermatozoon. During these divisions important departures from the typical method of mitosis occur. These departures SPERMATOGENESIS. 31 have been most thoroughly studied in the lower forms, but it is probable that they are fundamentally similar in the mammalia. It has already been pointed out (p. 22) that the number of chromosomes which appear dur- Fig. 7. — Diagram Illustrating the; Reduction of the Chromo- somes During Spermatogenesis. sc 1 , Spermatocyte of the first order; sc°, spermatocyte of the second order; sp, spermatid. ing the mitoses of the somatic cells is characteristic for the species. In the division of the primary spermato- cytes the number of chromosomes which appear is ap- parently only half the characteristic number, but in real- ity it is double that number, since each chromosome is 3^ THE DEVELOPMENT OF THE HUMAN BODY. hi really composed of four elements more or less closely united to form a tetrad. During the mitosis each tetrad divides into two dyads, one of which passes into each secondary spermatocyte, and these cells undergoing division without the usual reconstruction of the nu- cleus, each of the dyads which they contain is halved, so that each spermatid re- ceives a number of single chromosomes equal to half the number characteristic for the species. This reduc- tion of the chromosomes of the germ cells may be un- derstood from the annexed diagram (Fig. 7), which rep- resents the spermatogenesis of a form whose somatic cells are supposed to con- tain eight chromosomes. The transformation of the spermatids into spermatozoa takes place while they are in intimate association with the Sertoli cells, a number of them fusing with the cyto- plasm of an enlarged Sertoli cell, as shown in Fig. 6, s, and probably receiving nutrition from it. In each sper- matid there is present, in addition to the nucleus, an archoplasm sphere from which the centrosomes have migrated so as to lie free in the cytoplasm. The details of the transformation are still to a certain extent under discussion, the view here presented being only one of the Fig. 8. — Four Stages in the Transformation op a Sper- matid into the Spermato- zoon op a Rat. a, Archoplasm ; c, mass of chro- matin which is later absorbed ; /, axial filament; /;, head; he, head-cap; mp, middle-piece. — (von Lenhossek.) SPERMATOGENESIS. 33 many which have been advanced within recent years. On the fusion of the spermatid with a Sertoli cell, a deli- cate filament (Fig. 8, /), the beginning of the axial fila- ment of the spermatozoon, appears in its cytoplasm, seeming to rise from the centrosome which lies at one end of it. The archoplasm sphere (a) and centrosome migrate to opposite sides of the nucleus, which gradually assumes an excentric position, and the archoplasm be- comes converted into the head-cap (he) while the cen- trosomes enlarging form the anterior portion or neck of the middle-piece imp), the remainder of that structure being formed from the axial filament surrounded by a cytoplasmic sheath. As the axial filament lengthens the cytoplasm is drawn out with it to form its sheath, the terminal portion of the filament only projecting beyond the sheath to form the end-piece, and the cytoplasm surrounding the nucleus becomes reduced to an exceed- ingly delicate layer, so that the head of the spermato- zoon (h) consists almost entirely of nuclear substance if the head-cap be left out of consideration. The homologies of the parts of the spermatozoon with those of the spermatid may be presented in tabular form thus: Spermatid. Spermatozoon. Nucleus. Head. Archoplasm. Head-cap. Centrosome. Neck of middle-piece. f Axial filament. Cytoplasm. -] Sheath of middle-piece. (. Sheath of tail. The spermatozoon is, then, one of four equivalent cells, produced by two successive divisions of a primary sper- matocyte and containing one-half the number of chromo- somes characteristic for the species. The Ovum. — The human ovum is a spherical cell meas- 3 34 THE DEVELOPMENT OF THE HUMAN BODY. uring about 0.2 mm. in diameter and is contained within a cavity situated 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 '.- ~-z y j.'i ,,■£.%< "°V-'u "i$3v' m. 77zy_ ! ', SS^?5?F* 4% '.'"'■ j-Z Fig. 9. — Section through Portion of an Ovary of an Opossum (Didelphys virginiana) 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. in the ovarian stroma, and an inner one, the theca interna, composed of numerous spherical and fusiform cells. Both the thecse 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 trans- parent,^ thin, and structureless hyaline membrane, within THE OVUM. 3 5 which is the follicle proper, whose wall is formed by a layer of cells termed the stratum granulosum (Fig. 9, tng) and inclosing a cavity filled with an albuminous fluid, the liquor folliculi. At one point, usually on the surface nearest the center of the ovary, the stratum granulosum ^ Fig. 10. — Ovum from Ovary op a Woman Thirty Years op Age. cr, Corona radiata; «, nucleus; p, protoplasmic zone of ovum; ps, peri- vitelline space; y yolk; zp, zona pellucida. — (Nagel.) is greatly thickened to form a mass of cells, the discus proligerus {dp), which projects into the cavity of the folli- cle and encloses the ovum (0) . Usually but a single ovum is contained in any discus, though occasionally two or even three may occur. 36 THE DEVELOPMENT OF THE HUMAN BODY. The cells of the discus proligerus are for the most part more or less spherical or ovoid in shape and are arranged irregularly. In the immediate vicinity of the ovum, however, they are more columnar in form and are ar- ranged in about two concentric rows, thus giving a some- what radiated appearance to this portion of the discus, which is termed the corona radiata (Fig. 10, cr). Imme- diately within the corona is a transparent membrane, the zona pellucida (Fig. 10, 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 which has been held to be due to minute pores traversing the membrane 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. 10, p) and an inner deutoplasmic mass (y) which contains numer- ous fine granules of fatty and albuminous natures. These granules represent the food yolk or deutoplasm, 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 of the ovum (n) is situated somewhat excentrically in the deutoplasmic portion of the ovum and contains a single, well-defined nucleolus. A follicle with the structure described above and con- taining 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 fertilization, 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 OVULATION AND ITS RELATION TO MENSTRUATION. 37 describing the phenomena of maturation of the ovum it will be well to consider the extrusion of the ovum and the changes which the follicle subsequently undergoes. Ovulation and its Relation to Menstruation. — 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 development a follicle is situated somewhat deeply in the stroma of the ovary, but during its growth it approaches the surface and eventually forms a marked prominence, only an exceedingly thin membrane separat- ing the cavity of the follicle from the abdominal cavity. This thin membrane finally ruptures, and the liquor folli- culi, which is apparently under some pressure while con- tained within the follicle, rushes out through the rupture, carrying with it the ovum surrounded by some of the cells of the discus proligerus. The immediate cause of the bursting of the follicle is not yet clearly understood. It has been suggested that a gradual increase of the liquor folliculi under pressure must in itself finally lead to a rupture, and it has also been pointed out that just before the maturation of the follicle the theca interna undergoes an exceedingly rapid develop- ment and vascularization which may play an important part in the phenomenon. 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 de- velopment. Occasionally, however, 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 undergo development, producing an abdominal 38 THE DEVELOPMENT OF THE HUMAN BODY. 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 pregnancy are, of course, exceedingly serious, since in none of them is the fetus viable. It was long believed that ovulation was coincident with certain periodic changes of the uterus which constitute what is termed menstruation. 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 factors, and after it has once appeared it normally recurs at definite intervals more or less closely corresponding with lunar months {i. e., at intervals of about twenty-eight days, the extremes being from twenty-four to thirty-four days) until somewhere in the neighborhood of the fortieth or forty-fifth year, when it ceases. The structural changes associated with menstruation consist of a preliminary thickening of the walls of the uterus, its mucous membrane and the subjacent tissue becoming highly vascular and eventually congested. Later the walls of the blood-vessels degenerate and permit of an escape of blood here and there -beneath the mucous membrane which, in the areas overlying the effused blood, undergoes a fatty degeneration and is desquamated, allow- ing of the formation of a blood-clot in the cavity of the uterus. The hemorrhagic portion of the process lasts usually from three to five days; at its close a regeneration of the lost portions of the mucous membrane begins, and when this is completed a resting period ensues which per- sists until near the time of a new menstrual period. The local structural changes of the uterus are associated OVULATION AND ITS -RELATION TO MENSTRUATION. 39 -with decided constitutional disturbances. The pulse, blood-pressure, temperature, muscular power, and lung capacity are in general somewhat increased before men- struation and sink immediately before or at the time when the hemorrhage in the uterus begins; immediately before the menstrual period there is also a diminished destruction of the nitrogenous materials of the body, as shown by the amount of nitrogen excreted being less than at other times. These general changes may well affect the ovary as well as other portions of the body and so contribute to a coin- cidence of menstruation and ovulation. And, indeed, there seems little question but that the coincidence is of frequent or even usual occurrence. The appearance of menstruation indicates, as a rule, the beginning of fertil- ity, and sterility ensues at the time of the final cessation of the menses. Furthermore, menstruation ceases when pregnancy supervenes, and the cessation persists not only until parturition, but so long as the child remains un- weaned, and as a rule ovulation is also in abeyance during the same period. Exceptions, however, have been ob- served which show that the coincidence of the two phe- nomena is not invariable,' pregnancy, for example, having occurred in young girls who had not yet menstruated, and in forty-two operated cases in which the ovaries and uterus had been removed after menstruation, twelve showed no signs of ovulation as determined by the pres- ence of recently ruptured follicles in the ovaries (Leopold and Mironoff), while in another set of fifty-four cases ovulation appeared to have coincided with menstruation in thirty-nine instances. From the evidence at present at our disposal it may be stated that in the human species while ovulation generally coincides with menstruation, yet the two phenomena 4Q THE DEVELOPMENT OF THE HUMAN BODY. may, and not infrequently do, occur independently of one another. The Corpus Luteum. — 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. 1 1 ). On the rupture of the follicle a considerable portion of the stratum granulosum remains in place, and usually there is an effusion of a greater or less amount of blood from the vessels of the theca interna into the follicular cavity. The split in the wall through which the ovum escaped soon closes over and the cavity becomes filled with cells separated into groups by trabe- cular of connective tissue containing blood-vessels (Fig. 12). These cells contain a considerable amount of a peculiar yel- low pigment known as lutein, the color imparted to the follicle by this substance having suggested the name corpus luteum which is now applied to it. In later stages there is a gradual increase in the amount of connective tissue present and a corresponding diminu- tion of the lutein cells, the corpus luteum gradually losing its yellow color and becoming converted into a whitish, fibrous, scar-like body, the corpus albicans, which may eventually almost completely disappear. These various changes occur in every ruptured follicle, whether or not the ovum which was contained in it be fertilized. But Fig. 1 1. — Ovary op a Woman Nine- teen Years op Age, Eight Days after Menstruation. d, Blood-clot; /, Graafian follicle; th, theca. — (Kollmann.) THE CORPUS LUTEUM. 4 1 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 cor- pora 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 retro- Fig. 12. — Section 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.) gression of the follicle is completed usually in about three weeks, while the corpora vera persist throughout the en- tire duration of the pregnancy and complete their retro- gression after the birth of the child. 4 42 THE DEVELOPMENT OF THE HUMAN BODY. Two very different views are held as to the origin of the lutein cells. According to one, which may be termed von Baer's view, the cells of the stratum granulosum remain- ing in the follicle rapidly undergo degeneration and com- pletely disappear, and the lutein cells and connective- tissue trabeculae are formed entirely from the cells of the theca interna, which increase rapidly both in size and number. The other view was first advanced by Bischoff and may be known by his name. It is to the effect that the granulosa cells do not disintegrate, but, on the con- trary, increase rapidly in number and become converted into the lutein cells, only the connective tissue and the blood-vessels being derived from the theca interna. Which of these two views is correct is at present uncer- tain. The majority of those who have within recent years studied the formation of the human corpus luteum have expressed themselves in favor of von Baer's theory. Sobotta has, however, made a thorough study of the phe- nomena in a perfect series of mice ovaries and has demon- strated that in that form the lutein cells are derived from the granulosa cells. It would seem strange if the lutein cells had a different origin in two different mammals, and the observations on mice are so thorough that one is tempted to regard different results as being due to imper- fections in the series of ovaries studied, important steps in the development of the corpora lutea being thus over- looked. Still the evidence available renders a resistance to the temptation advisable, and the possibility of both views being correct — the one in some cases, the other in others — must be entertained. Indeed, it has very re- cently been suggested that the rapidity with which the retrogressive changes ensue in small animals compared with larger ones may be sufficient to account for marked differences in the mode of origin of the lutein cells in dif- THE MATURATION OF THE OVUM. 43 ferent cases. If this possibility be accepted, then it may be said that the weight of evidence is in favor of the cor- rectness of von Baer's views in the case of the human species. The Maturation of the Ovum. — Returning now to the ovum, it has been shown that at the time of its extrusion from the Graafian follicle it is not equivalent to a sperma- tozoon but to a primary spermatocyte, and it may be remembered that such a spermatocyte becomes converted into a spermatozoon only after it has undergone two divi- sions, during which there is a reduction of the number of the chromosomes to one-half the number characteristic for the species. Similar divisions and a similar reduction of the chromo- somes 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 mam- mals only with any approach to completeness in the mouse (Sobotta) ; but they have been observed in so many other forms, both vertebrate and invertebrate, and pre- sent in all cases so much uniformity in their general features, that there can be little question as to their occur- rence in the human ovum. In typical cases the ovum (the primary oocyte) under- goes a division in the prophases of which the chro- matin aggregates to form half as many tetrads as there are chromosomes in the somatic cells (Fig. 13, oc 1 ) and at the metaphase a dyad from each tetrad passes into each of the two cells that are formed. These two cells (secondary oocytes) are not, however, of the same size; one of them is almost as large as the original pri- mary oocyte and continues to be called an ovum (oc 2 ), while the other is very small and is termed a polar globule (p). A second division of the ovum quickly succeeds 44 THE DEVELOPMENT OF THE HUMAN BODY. the first (Fig. 13, oc 2 ), and each dyad gives a single chro- mosome to each of the two cells which result, so that each of these cells possesses half the number of chromosomes characteristic for the species. The second division, like ((m ^B) m Fig. 13. — Diagram Illustrating the Reduction of the Chromo- somes during the Maturation of the Ovum. 0, Ovum; oc 1 , oocyte of the first generation; oc 2 , oocyte of the second generation; p, polar globule. 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 globule. Frequently the THE MATURATION OF THE OVUM. 45 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 maturation four cells are formed (Fig. 13), the mature ovum (0), and three polar globules (p), each of which contains half the number of chromosomes characteristic for the species. The similarity of the maturation phenomena to those of spermatogenesis may be perceived from the following diagram : n/"~N Spermato- I I cyte I Spermato- cyte II Oocyte II O O O O OvutnW O U O OO O O Spermatids Polar globules In both processes the number of cells produced is the same and in both there is the same reduction of the chromo- somes. But while each of the four spermatids is func- tional, the three polar globules are non-functional, and are to be regarded as abortive ova formed during the pro- cess of reduction of the chromosomes only to undergo 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, the amount of nutritive material and cytoplasm necessary for successful develop- ment. In the mouse, which for the present must be taken as type of the mammalia, the majority of ova show an im- 46 THE DEVELOPMENT OF THE HUMAN BODY. portant departure from the processes just described. The number of chromosomes occurring in the somatic cells of the mouse is apparently twenty-four. The first matur- ation spindle (Fig. 14) possesses twelve chromosomes, which from analogy with the lower forms may be assumed Fig. 14. — Ovum op a Mouse Showing the Maturation Spindle. The ovum is enclosed by the zona pellucida (zp) , to which the cells of the corona radiata are still attached. — (Sobotta). to be tetrads, and during the metaphase each chromo- some divides transversely, the polar globule receiving twelve chromosomes, presumably dyads, while twelve re- main within the ovum. So far the process is essentially typical, but in 90 per cent, of the ova examined this was the only maturation division which took place, only one THE FERTILIZATION OF THE OVUM. 47 polar globule being formed. In the remaining 10 per cent, the second division occurred, the twelve chromo- somes again dividing transversely, so that the second polar globule and the ovum each received twelve chromo- somes and the reduction was typical. The occurrence of but one maturation division in an immense majority of ova is difficult to explain and de- mands further study. Possibly in these ova the supposed tetrads are in reality dyads and the reduction differs only quantitatively from the typical process. 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 occasion- ally, and, as a matter of fact, such a restoration occurs at the very beginning of the development 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. The fertilization of the human ovum has not yet been observed, but the phenomenon has been repeatedly studied in lower forms, and a thorough study of the process has been made on the mouse by Sobotta, whose observations are taken as a basis for the following account. The maturation of the ovum is quite independent of fertilization, but in many forms the penetration of the spermatozoon into the ovum takes place before the ma- turation phenomena are completed. 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 rko -■ d^mmr-^ f r * a w tdi spk — ^ .-y *; * * , t * SI ,. it- ••■•SV:.' - ■.'•■:■•■ ■ *■■■■;■ .-.■•■?■.• '.r •■*v A B Fig. 22. — Two Stages in the Gastrulation of Amphioxus. — (Morgan and Hazcn.) pearance. It arises as a lateral fold (mp) of the dorsal surface of the endoderm (en) on each side of the middle line as indicated in the transverse section shown in Fig. 23. This fold eventually becomes completely constricted off from the endoderm and forms a hollow plate occupying the space between the ectoderm and endoderm, the cavity which it contains being the body-cavity or cazlom. In the amphibia, where the amount of yolk is very much greater than in Amphioxus, the gastrulation be- comes considerably modified. On the line where the large- 6 66 THE DEVELOPMENT OF THE HUMAN BODY. and small-celled portions of the blastula become con- tinuous a crescentic groove appears and deepening forms an invagination (Fig. 24, 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 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 en- closes the larger ones, it becomes smaller and is finally represented by a small opening situated at what will be the hind end of the embryo. Soon after the archen- teron has been formed a pouch.— (Hatschek.) ally splitting into two lay- ers, arises from its roof on each side of the median line and grows out with the space between the ectoderm and endoderm (Fig. 25, mk 1 and mk 2 ) 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. 24, mes). Fig. 23. — Transverse Section op Amphioxus Embryo with Five Mesodermic Pouches. Ch, Notochord; d, digestive cavity; THE FORMATION OF THE GERM LAYERS. 6/ As the 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 Fig. 24. — Section Through a Gastrula of Amblystoma. dli Dorsal lip of blastopore; gc, digestive cavity; gr, area of mesoderm formation; mes, mesoderm. — (Eycleshymer.) 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 the two are continuous imme- diately in front of the definitive blastopore. In the reptilia still greater modifications are found in the method of formation of the germ layers. Before the enveloping cells have completely surrounded the yolk- 68 THE DEVELOPMENT OF THE HUMAN BODY. mass, a crescentic groove, resembling that occurring in amphibia, appears near the posterior edge of the blasto- derm, 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. 26, ec) and a subjacent mass of somewhat scattered cells. Later the lowermost cells of this subjacent mass arrange themselves in a con- tinuous layer constituting what is termed the primary V Fig. 25. — Section through an Embryo Amphibian (Triton) of 2\ Days, showing the Formation of the GasTral Mesoderm. ak, Ectoderm; ch, chorda endoderm; dk, digestive cavity; ik, endo- derm; mk 1 andmk 2 , splanchnic and somatic layers of the meso- derm. D, dorsal and V, ventral. — (Hertwig.) endoderm (en 1 ), 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 endoderm, the extent of this invagination being, however, very different in different species. In the gecko (Will) it pushes forward between the ectoderm and primary endoderm almost to the anterior edge of the THE FORMATION OF GERM LAYERS. 69 blastoderm, but later the cells forming its floor, together with those of the primary endoderm immediately below, undergo a degeneration, the roof cells at the lateral mar- gins of the invagination becoming continuous with the persisting portions of the primary endoderm. This layer, following the enveloping cells in their growth over the yolk-mass, gradually surrounds that structure so that prm - ! V ' ^^ ■ " ** en! en prm 0M§&gg&W> VlVf-iLTV—t Fig. 26. — Longitudinal Sections through Embryos of the Gecko, showing Gastrulation. ec, Ectoderm ; en, secondary endoderm ; en', primary endoderm ; prm, prostomial mesoderm. — {Will.) 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 archenteron. This interest- ing abbreviation of the process occurring in the gecko indicates the mode of development which is found in the mammalia. ;o THE DEVELOPMENT OF THE HUMAN BODY. The existence of a prostomial mesoderm in connection with the primitive streak has already been noted, and when the invagination takes place it is carried forward as a narrow band of cells on each side of the sac of secondary endoderm. After the absorption of the ventral wall of the invagination a folding or turning in of the margins of the secondary endoderm occurs (Fig. 27) whereby its Fig. 27. — Diagrams Illustrating the Formation op the Gastral Mesoderm in the Gecko. ce, Chorda endoderm; ec, ectoderm; en, secondary endoderm; en 1 , primary endoderm; gm, gastral mesoderm. — (Will.) lumen becomes reduced in size and it passes off on each side into a double plate of cells which constitute the gas- tral 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 has its origin from the ectoderm covering the yolk outside the limits of the blastoderm proper, a mode of origin which serves to explain the phenomena later to be described for the mammalia. THE FORMATION OF GERM LAYERS. 7 1 In comparison with the amphibians and Amphioxus, the reptilia present a subordination of the process of in- vagination in the formation of the endoderm, a primary endoderm making its appearance 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 blasto- derm of the reptilian ovum, and the first differentiation which appears in it concerns the cells situated next the cavity of the vesicle, these cells uniting to form a distinct layer which gradually extends so as to form a complete lining to the inner surface of the enveloping cells (Fig. 28, A). These cells are endodermal and correspond to the primary 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 imme- diately beneath Rauber's cells (Fig. 28, 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. 28, 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 de- velopment 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. 72 THE DEVELOPMENT OF THE HUMAN BODY. While these changes have been taking place a splitting of the enveloping layer has occurred, so that the wall of v*®^' Fig. 28. — Suctions of Ova of a Bat showing (A) the Formation of the Endoderm and (B and C) of the Amniotic Cavity. — {Van Beneden. ) the ovum is now formed of three layers, an outer one which may be termed the trophoblast, a middle one which THE FORMATION OF THE GERM LAYERS. 73 probably is transformed into the extra-embryonic meso- derm of later stages, though its significance is at present somewhat obscure, and an inner one which is the primary endoderm. In the bat, of whose ovum Fig. 28, C, repre- sents a section, that portion of the middle layer which forms the roof of the amniotic cavity disappears, only the Fig. 29. — A, Side View of Ovum op Rabbit Seven Days Old (Kolliker) ; B, Embryonic Disk op a Mole (Heape) ; C, Embryonic Disk op a Dog's Ovum of about Fifteen Days {Bonnet), ed, Embryonic disk; hn, Hensen's node, mg, medullary groove; ps, primitive streak ; to, vascular area. trophoblast persisting in this region, but in another form this is not the case, the roof of the cavity being composed of both the trophoblast and the middle layer. A rabbit's ovum in which there is yet no amniotic cavity and no splitting of the enveloping layer shows, when viewed from above, a relatively small dark area on the surface, which is the embryonic disk. But if it be looked 74 THE DEVELOPMENT OF THE HUMAN BODY. at from the side (Fig. 29, A), it will be seen that the upper half of the ovum, that half in which the embryonic disk 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 extended 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 em- bryonic disk, produced by a proliferation of cells in this region and having a somewhat crescentic 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 primi- Fig. 30. — Posterior Portion op a Longitudinal Section through the Embryonic Disk op a Mole. hi, Blastopore; ec, ectoderm; en, endoderm; prm, prostomial meso- derm. — {After Heape.) tive streak( Fig. 29, 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. 29, 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. To understand the meaning of these various dark areas recourse must be had to the study of sections. A longi- tudinal section through the embryonic disk of a mole ovum at the time when the crescentic area makes its ap- THE FORMATION OF THE GERM LAYERS. 7$ pearance is shown in Fig. 30. 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 prim- ary endoderm {en) can be clearly distinguished, while behind it no such distinction of the two layers is visible. This stage, then, may be regarded as comparable to the invagination stage of the reptilian ovum, the blastopore being, however, much less developed, and the region be- hind the blastopore will correspond to the reptilian primi- tive streak. The later forward extension of the primitive streak is supposed to be due to the mode of growth of the embryonic disk. Between the stages represented in Figs. > 1 1 > 1 1 1 1 v \ \ v / / / 1 Fig. 31. — Diagram Illustrating Concrescence. — (Duval.) 30 and 29, B, the disk has enlarged considerably and as growth proceeded there was a turning in, as it were, of the edges of the disk at its posterior end, whereby the primi- tive streak would be carried forward and elongated. This process, which is termed concrescence, will perhaps be understood more clearly from an inspection of Fig. 31 than from many lines of description. If this process of concrescence really occurs, then the point where the origi- nal rudimentary blastopore occurred is now situated far forward upon the embryonic disk, and Hensen's node indicates a proliferation of cells in the vicinity of the blastopore to form the prostomial mesoderm. 76 THE DEVELOPMENT OF THE HUMAN BODY. As regards the head process, it is a band of cells which grows forward from the region of the blastopore along the median line and replaces the primary endoderm in that situation (Fig. 32, chp). It corresponds, therefore, to the dorsal wall of the invagination of secondary endoderm in the reptile, the ventral wall of the invagination not developing at all, a condensation of development already indicated in the turtle (see p. 69). Indeed, in the gecko, the turtle, and the mammal we have three degrees of sim- plification of a process. In the gecko a sac-like invagina- tion extends nearly to the anterior edge of the embryonic § -V • ^•■— :i* w ^ '*••■ « -*"->■'* m^ ■ op. Fig. 32. — Transverse Section of the Embryonic Area of a Dog's Ovum at about the Stage of Development shown in Fig. 29, C. The section passes through the head process (Chp) ; M, mesoderm. — (Bonnet.) disk and its ventral wall later disappears; in the turtle the invagination is comparatively slight and the useless ventral wall is only partly developed; and, finally, in the mammal (Fig. 33) the invagination is practically non- existent and no ventral wall whatsoever is formed, only the dorsal wall (ce) growing forward. It should be stated that in some mammals apparently the most anterior por- tion of the roof of the archenteron is formed directly from the cells of the primary endoderm, which in this region are not replaced by the head process, but aggregate to THE FORMATION OF THE GERM LAYERS. 77 form a compact plate of cells with which the anterior ex- tremity of the head process unites. Such a condition would represent a further modification of the original condition. As regards the formation of the mesoderm it is possible to recognize both the prostomial and gastral mesoderm in the mammalian ovum, though the two parts are not so clearly distinguishable as in lower forms. It has already been seen that Hensen's node probably indicates the ex- istence of a mass of prostomial mesoderm, and when the head process grows forward it carries with it some of this Fig. 33. — Diagram of a Longitudinal Section through the Em- bryonic Disk of a Mole. am, Amnion; ce, chorda endoderm; ec, ectoderm; nc, neurenteric canal ps, primitive streak. — {Heape.) tissue. But, in addition to this, a contribution to the mesoderm is also apparently furnished by the cells of the head process in the form of lateral plates situated on each side of the middle line. These plates are at first solid (Fig. 34, gm), but their cells quickly arrange themselves in two layers, between which a ccelomic space later appears. Furthermore, as has already been pointed out, the layer of enveloping cells splits into two concentric layers, the inner of which seems to be mesodermal in its nature and forms a layer lining the interior of the trophoblast and lying between this and the primary endoderm. This layer is by no means so evident in the lower forms, but is 78 THE DEVELOPMENT OF THE HUMAN BODY. perhaps represented in the reptilian ovum by the cells which underlie the ectoderm in the regions peripheral to the blastoderm proper (see p. 70). The Significance of the Germ Layers. — The formation of the three germ layers is a process of fundamental impor- tance, 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 Fig. 34. — Transverse Section through the Embryonic Disk of a Rabbit. ck, Chorda endoderm; ee, ectoderm; en, endoderm; gin, gastral meso- derm. — {After van Beneden.) principally nutritive functions. In certain of the lower invertebrates, the class Coelentera, 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, while the remaining functions, supportive, excretory, loco- motor, reproductive, etc., are assumed by the mesoderm. The manifold adaptations of development obscure in THE SIGNIFICANCE OF THE GERM LAYERS." 79 certain cases the fundamental relations of the three layers, certain portions of the mesoderm, for instance, failing to differentiate simultaneously with the rest of the layer and appearing therefore to be a portion of either the ectoderm or endoderm. But, as a rule, the layers are structural units of a higher order than the cells, and since each as- sumes definite physiological functions, definite structures have their origin from each. Thus from the ectoderm there develop : The epidermis and its appendages, hairs, nails, epider- mal glands, and the enamel of the teeth. The mucous membrane lining the mouth and the nasal cavities, as well as that lining the lower part of the rectum. The nervous system and the nervous elements of the sense-organs, together with the lens of the eye. From the endoderm develop : The mucous membrane lining the digestive tract in general, together with the epithelium of the various glands associated with it, such as the liver and pancreas. The lining epithelium of the larynx, trachea, and lungs. The epithelium of the bladder and urethra. From the mesoderm there are formed : The various connective tissues, including bone and the teeth (except the enamel). The muscles, both striated and non-striated. The circulatory system, including the blood itself and the lymphatic system. The lining membrane of the serous cavities of the body. The kidneys and ureters. 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 80, THE DEVELOPMENT OF THE HUMAN BODY. a definite layer, while in other structures its cells are scattered in a matrix of non-cellular material, as, for ex- ample, in the connective tissues, bone, cartilage, and the blood and lymph. It has been proposed to distinguish these two forms of mesoderm as mesothelium and mesen- chyme respectively, a distinction which is undoubtedly convenient, though probably devoid of the fundamental importance which has been attributed to it by some em- bryologists. LITERATURE. R. AsshETOn: "A Reinvestigation into the Early Stages of the Develop- ment of the Rabbit," Quarterly Journ. of Microsc. Science, xxxvii, 1894. R. Assheton: "The Development of the Pig During the First Ten Days," Quarterly Journ. of Microsc. 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. of Microsc. Science, xli, 1898. E. van BenEden: "Recherches sur les premiers stades du developpement du Murin (Vespertilio murinus)," Anatbm Anzeiger, xvi, 1899. R. Bonnet: "Beitrage zur Embryologie der Wiederkauer gewonnen am Schafei," Archiv fur Anat. und Physiol., Anat. Abth., 1884 and 1889. R. Bonnet: "Beitrage zur Embryologie des Hundes," Anat. Hefte, ix, 1897 G. Born: "Erste Entwickelungsvorgange," Ergebnisse der Anat. und Entwicklungsgesck., I, 1892. A. C. EycleshymER: "The Early Development of Amblystoma with Observations on Some Other Vertebrates," Journ. of Morphol., x, 1895. B. HaTschEk: "Studien iiber Entwicklung des Amphioxus," Arbeiten aus dem zoolog. Instil, zu Wien, iv, 1881. W. HE APE: "The Development of the Mole (Talpa europaea)," Quarterly Journ. of Microsc. Science, xxm, 1883. A. A. W. Hubrecht: "Studies on Mammalian Embryology II: The De- velopment of the Germinal Layers of Sorex vulgaris," Quarterly Journ. of Microsc. Science, xxxi, 1890. F. Keibel: "Studien zur Entwickelungsgeschichte des Schweines," Mor- pholog. Arbeiten, in, 1893. K. Mitsukuri and C. Ishikawa: "On the Formation of the Germinal Layers in Chelonia," Quarterly Journ. of Microsc. Science, xxvil, 1887. LITERATURE. 8 1 E. SelEnka: "Studien iiber Entwickelungsgeschichte der Thiere,'' 4tes Heft, 1886-87; 5tes Heft, 1891-92. J. Sobotta: "Die Befruchtung und Furchung des Eies der Maus," Archiv ]v,r mikrosk. Anat., xlv, 1895. J. Sobotta: "Die Furchung des Wirbelthiereies," Ergebnisse der Anat. und Entwickelungsgeschichte., vi, 1897. L. Will: "Beitrage zur Entwicklungsgeschichte der Reptilien," Zoolog. Jahrbilcher, Abth. fiir Anat., vi, 1893. CHAPTER III. THE DEVELOPMENT OF THE EXTERNAL FORM OF THE HUMAN EMBRYO. The youngest human ovum at present known is that described by Peters. It was taken from the uterus of a y-.. am crn- Fig. 35. — Section of Embryo and Adjacent Portion of an Ovum of 1 MM. am, Amniotic cavity; ce, chorionic ectoderm; cm, chorionic mesoderm ;ec, embryonic ectoderm ; en, endoderm ; m, embryonic mesoderm ; ys, yolk-sac. — {Peters.) 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. 35, ce) was lined by a layer of mesoderm (cm), which, 82 THE EXTERNAL FORM OF THE BODY. 83 on the surface furthest away from the uterine cavity, was considerably thicker 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 (aw), 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 em- bryonic ectoderm (ec). Immediately below this was a Fig. 36. — Diagrams to show the Probable Relationships op the Parts in the Embryos Represented in Figs. 28, C, and 35. Ac, Amniotic cavity; C, extra-embryonic body-cavity; Me, (in figure to the left) mesoderm, (in figure to the right) somatic mesoderm; Me', splanchnic mesoderm ; D, digestive tract ; En, endoderm ; T, tropho- blast. The broken line in the mesoderm of the figure to the left in- dicates the line along which the splitting of the mesoderm occurs. layer of mesoderm (to) which split at the edge of the em- bryonic disk into two layers, one of which became con- tinuous with the mesodermic thickening and so with the layer of mesoderm lining the interior of the trophoblast, while the other enclosed a sac lined by a layer of endo- dermal cells and termed the yolk-sac (ys). The total length of the embryo was 0.19 mm., and so far as its ecto- derm and mesoderm are concerned it might be described as a flat disk resting on the surface of the yolk-sac, though 84 THE DEVELOPMENT OF THE HUMAN BODY. 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 primi- tive streak formation, before the development of the head process. On comparing it with the ovum of a bat in ap- proximately the stage of development represented in Fig. 28, C, it will be seen to present some important advances (Fig. 36). It seems clear that the yolk-sac is equivalent to what was the cavity of the ovum in the earlier stages, and consequently the cavity (c) into which the yolk-sac projects is unrepresented in the bat's ovum. How this cavity is formed can only be conjectured, but it seems probable that it arises by the splitting of the layer of cells which lines the interior of the trophoblast in the bat's ovum (or perhaps by the vacuolization of the central cells of this layer) and the subsequent accumulation of fluid between the two mesodermal layers so formed. How- ever that may be, it seems clear that the size of the human ovum is due mainly to the rapid growth of this cavity, which, as future stages show, is the extra-embryonic portion of the body-cavity, the splitting or vacuolization of the mesoderm by which it is probably formed being the precocious appearance of the typical splitting of the meso- derm to form the embryonic body-cavity which, as will be seen in a subsequent chapter, takes place only at a later stage of development. From now on the tropho- blast and the layer of mesoderm lining it may together be spoken of as the chorion, the mesoderm layer being termed the chorionic mesoderm. A human embryo of a somewhat greater age (Fig. 37), measuring about 0.37 mm. in length, has been described by Graf Spee as embryo v.H., and was taken from an ovum estimated to measure 6 by 4.5 mm. in diameter. Notwithstanding the much greater size of the ovum, THE EXTERNAL FORM OF THE BODY. 85 which is due to the continued increase in the size of the extra-embryonic ccelom, the embryo is but little advanced beyond the stage which the Peters' embryo had reached, and is probably in a late stage of the development of the primitive streak. Confining the attention for the present solely to the embryo and the immediately adjoining parts, it will be seen that the thickening of the chorionic meso- derm which encloses the amniotic cavity has increased in Fig. 37. — Ovum Measuring 6 >( 4.5 mm. The Left Half of the Chorion has Been Re- moved to show the Embryo. a, Amniotic cavity; 6, belly-stalk; c, chorion ; e, embryonic disk ; v, chorionic villus; y, yolk-sac. — (von Spec.) Fig. 38. — Embryo 1.54 mm. in Length, from the Dorsal Surface. a, Amnion ; m, medullary groove ; nc, neurenteric canal; ps, primi- tive streak; y, yolk-sac. — (von Spec.) size and now forms a pedicle, known as the belly-stalk (b), at the extremity of which is the yolk-sac (y). Further- more, the amniotic cavity (a) now lies somewhat excen- trically in this pedicle, being near what maybe spoken of as its anterior surface. The embryo still possesses a dis- coidal form and may still be described as a flat disk float- ing on the surface of the yolk-sac. This same general form is preserved in another embryo, known as embryo Gle, described by Graf Spee, which 86 THE DEVELOPMENT OF THE HUMAN BODY. measured 1.54 mm. in length (Fig. 38). In it, however, the more median portion of the embryonic disk has be- come thicker and is separated from the more peripheral portions by a distinct furrow. From the more median or axial portion the embryo proper will develop, and this por- tion is now shaped somewhat like the body of a violin and presents at its posterior portion the remains of the primi- Fig. 39. — 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. tive streak, near the anterior end of which is a distinct pore, the opening of what is termed the neurenteric canal (nc), a description of which will be found in a subsequent chapter (p. 112). More anteriorly two longitudinal ridges have appeared, the first indications of which are termed the medullary folds. In later stages a separation or constriction of the em- bryo from the yolk-sac begins and results in the trans- formation of the discoidal embryonic portion of the em- THE EXTERNAL FORM OF THE BODY. 87 bryonic 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 pro- ceeds most rapidly at the anterior end of the body, as shown in the diagrams (Fig. 39), and least rapidly at the posterior end where the belly-stalk is situated, and pro- duces a constriction of the yolk-sac, the portion of that structure nearest the embryonic disk becoming enclosed within the body of the embryo to form the digestive tract, while the remainder is con- verted into a pedicle-like por- tion, the yolk-stalk, at the ex- tremity of which is the yolk- vesicle. The further continu- ance of the folding in of the edges of the embryonic area Fig. 40.— Embryo 2.5 mm. Long. , , . , am. Fragment of the torn am- leads to an almost complete nion; mg> medullary groove; closing in of the digestive J^ yolk-sac— (A lien Thomp- tract 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. An embryo which exhibits an early stage in the process of constriction has been described by Allen Thompson and is represented in Fig. 40.* It measured about 2.5 mm. in length and had reached a stage in which the medullary folds had become very pronounced and their edges had come into contact at one portion, although the anterior and posterior portions of the groove (mg) between them * It must be noted that in the figure neither the amnion (except for a small fragment still persisting in front) nor the belly-stalk is represented. 88 THE DEVELOPMENT OF THE HUMAN BODY. were still widely open. The embryo will be seen from the figure to project somewhat both in front of and behind the yolk-sac, although the greater part of its ventral surface is still formed by that structure. At the sides also it is well separated from the yolk-sac, and resting upon the sac in front is a swelling which represents the heart. In another embryo (Fig. 41), slightly smaller though Fig. 41. — Reconstruction of Embryo 2.11 mm. Long. al, Allantois; am, amnion; B, belly-stalk; ch, chorion; h, heart; ms, mesodermic somite ; os, oral fossa ; ph, pharynx ; v, chorionic villi; Y, yolk-sac. — (After Etemod.) evidently older than the preceding one, and described by Eternod, the edges of the medullary folds have not only come into contact throughout the greater portion of their length, but they have fused together, the groove between them being open only in front and behind. On each side of the median line eight somewhat oblong areas are to be THE EXTERNAL FORM OF THE BODY. 8 9 distinguished, caused by a transverse division of the sub- jacent mesoderm into what are termed mesodermic somites am Fig. 42. — Embryo 2.5 mm. Long. am, Amnion; B, belly -stalk; //, heart; M, closed, and M', still open portions of the medullary groove; Om, omphalo-mesenteric vein; OS, oral fossa; Y, yolk-sac. — (Kallmann.) (ms), structures which will be described in detail in the succeeding chapter. The separation of the embryo from go THE DEVELOPMENT OF THE HUMAN BODY. the yolk-sac (Y) has advanced considerably and the sac shows evident indications of constriction just where it meets the body of the embryo. The head projects more markedly beyond the anterior surface of the yolk-sac and is separated from the region occupied by the heart (h) am % Y. Fig. 43. — Embryo Lg, 2.15 mm. Long. am, Amnion; B, belly-stalk; C, chorion; /;, heart; Y, yolk-sac. — (His.) by a deep and well-marked depression, the oral fossa (os). In an embryo described by Kollmann (Fig. 42) and measuring 2.5 mm. in length,* the edges of the medullary folds (M) had come into contact throughout their entire * The embryo was measured only after having been preserved in alcohol, and the actual length was probably somewhat greater than this. THE EXTERNAL FORM OF THE BODY. . QI length, except for a short distance anteriorly (M 1 ), and thirteen mesodermic somites were visible. The constric- tion of the yolk-sac was even more pronounced than in the preceding embryo and the hind end of the body had become defined, the belly-stalk no longer seeming to be a posterior continuation of the body but arising from the posterior part of the ventral surface. The oral fossa (OS) was also more marked, and it may be noticed that the dorsal surface of the body was distinctly concave from before backward, a peculiarity which becomes more pro- nounced in a later stage and constitutes what is termed the dorsal flexure. This is well shown in an embryo described by His and named by him embryo lxviii (Lg) (Fig. 43). In it the yolk-sac forms a much smaller portion of the ventral sur- face than it did in earlier stages, and it has also become distinctly separated from the belly-stalk. The most peculiar feature of this embryo is, however, the dorsal flexure. This is apparently a normal feature and is probably produced by a difference in the rate of growth of the lateral and median portions of the outer layer of the embryonic mesoderm, the former portion fail- ing to keep pace with the growth of the latter, which becomes folded in accommodation to the strain. The flexure is of comparatively short duration, and when once it begins to disappear it seems to do so rapidly, the dorsal concavity suddenly becoming a convexity and the tension of the layer coming into equilibrium in the new position. One other feature is noteworthy in this em- bryo — namely, the occurrence of two linear vertical de- pressions a little behind the head region of the embryo; these are the first representatives of a series of branchial clefts. These structures are of great morphological importance, 92 THE DEVELOPMENT OF THE HUMAN BODY. inasmuch as they determine to a large extent the arrange- ment of various organs of the head region. They repre- sent 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 mammals they never have respiratory functions to perform, but, appearing, persist for a time and then either disappear or are ap- plied to some entirely dif- ferent purpose. Indeed, in man they are never really clefts but merely grooves, and corresponding to each groove in the ectoderm there is also one in the sub- jacent endoderm of what will eventually be the pharyngeal region of the di- gestive tract, so that in the region of each cleft the ecto- derm and endoderm are in close relation, being separated only by a very thin layer of mesoderm, while in the inter- vals between successive clefts a more considerable amount of mesoderm is present (Fig. 44). In the human embryo four clefts develop in each side of the body and five branchial arches, the last arch lying posteriorly to the fourth cleft and not being very sharply defined along its posterior margin. As just stated, the clefts are normally merely grooves, and in later development either disappear or are converted into Fig. 44. — Floor of the Pharynx of Embryo B, 7 mm Long. Ep, Epiglottis ; Sp, sinus pracervi- calis; t 1 , anterior, and r 2 , pos- terior portions of the tongue; /, II, III, and IV, branchial arches. —(His.) THE EXTERNAL FORM OF THE BODY. 93 Fig. 45. — Embryo Lr, 4.2 mm. Long. am, Amnion; au, auditory capsule; B, belly-stalk; /(, heart; LI, lower and VI, upper limb; Y, yolk-sac. — (His.) 94 THE DEVELOPMENT OF THE HUMAN BODY. 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 frequently developed from the lower (ventral) part of the first cleft; normally this disappears, the upper portion persisting, how- ever, to form the external auditory meatus and tympanic cavity. The embryo i^xvin (Lg) just described measured 2.1 1 mm. in length, this measurement, however, being taken along a straight line and not following the flexure of the body. It does not represent, therefore, the actual length of the body and there is much less difference between it and the next embryo described than is implied by the figures. This embryo (Fig. 45) is also one of those de- scribed by His and is known as embryo i^xvii (Lr). It measures 4.2 mm. in length and shows an almost complete disappearance of the dorsal flexure so marked in embryo lxviii. Instead of this, it presents a well-marked ventral bending of both the anterior and posterior portions of the body, so that the dorsal surface is prominently convex in the regions which will later be the nape of the neck and the sacral region, and consequently the convexities may be known as the neck bend and the sacral bend. Furthermore, there is noticeable a ventral projection of the extreme front end of the body, so that a third convexity occurs anteriorly to the neck bend and may be termed the head bend. The constriction of the yolk-sac has progressed, as has also its separation from the belly-stalk; the meso- dermic somites have almost reached their maximum development and are very distinct; the two branchial clefts present in the preceding embryo have increased in size and the third cleft has made its appearance; two THE EXTERNAL FORM OF THE BODY. 95 Fig. 46. — Embryo of from Twenty to Twenty-fivB Days. A m, Amnion; LL, lower limb ; UA, umbilical artery; Uc, umbilical cord; UL, upper limb; Ys, yolk-sac. — (Coste.) 96 THE DEVELOPMENT OF THE HUMAN BODY. small elevations of the sides of the body, one almost oppo- site the neck bend and the other opposite the sacral bend, are the first indications of the limbs (Ul and LI) ; and the eyeball and ear vesicle (au), which were present though not very evident in earlier stages, are now plainly visible in surface views. In the next stage — as a type of which an embryo Fig. 47. — Embryo 9.1 mm. Long. LI, Lower limb; U, umbilical cord; Ul, upper limb; Y, yolk-sac. — (His.) figured by Coste (Fig. 46) may be taken — the three bends of the body mentioned above have greatly increased, so that the head and tail of the embryo are almost in contact and the latter is bent a little toward one side. The closure of the ventral surface of the body is almost completed and THE EXTERNAL FORM OF THE BODY. 97 the margins of the umbilicus have begun to be prolonged ventrally so as to enclose the yolk-stalk and belly-stalk in the umbilical cord. The yolk-sac has increased con- siderably in length and the differentiation of its extra- embryonic portions into a yolk-stalk and yolk-vesicle is plainly distinguishable. The limb rudiments have in- creased somewhat in size, and, in addition to the eyeball and ear vesicle, a third sense-organ has made its appear- ance in the form of two pits situated on the under side of the anterior portion of the head; these pits are the first indications of the nasal fossce. The fourth branchial cleft has appeared and those formed earlier have elongated so that they almost reach the mid-ventral line, and from the dorsal part of the ante- rior border of the first arch a strong process has developed so that the arch on each side is somewhat <-shaped. The upper limb of each V is destined to give rise to the upper jaw, and hence is known as the maxillary process, while the lower limb represents the lower jaw and is termed the mandibular process. Leaving aside for the present all consideration of the further development of the limbs and branchial arches, the further evolution of the general form of the body may be rapidly sketched. In an embryo (Fig. 47) from Ruge's collection, described and figured by His and measuring 9.1 mm. in length,* the prolongation of the margins of the umbilicus has increased until more than half the yolk- stalk has become enclosed within the umbilical cord. The neck and sacral bends are still very pronounced, although * This measurement is taken in a straight line from the most anterior portion of the neck bend to the middle point of the sacral bend and does not follow the curvature of the embryo. It may be spoken of as the neck- rump length and is convenient for use during the stages when the embryo is coiled upon itself. 98 THE DEVELOPMENT OF THE HUMAN BODY. the embryo is beginning to straighten out and is not quite so much coiled as in the preceding stage. At the poste- rior end of the body there has developed a rather abruptly conical tail filament, in the place of the blunt and gradu- ally tapering termination seen in earlier stages, and a well- marked rotundity of the abdomen, due to the rapidly in- creasing 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 Fig. 48. — Embryo Br 2 , 13.6 mm. Long. — (His.) 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. 48 representing the embryo xlv (Br 2 ) of His, which shows also, both in front of and behind the neck bend, a distinct depression, the more anterior one being the occi- pital and the more posterior the neck depression; both these depressions are the expressions of changes taking THE EXTERNAL FORM OF THE BODY. 99 place in the central nervous system. The tail filament has become more marked, and in the head region a slight ridge surrounding the eyeball and marking out the con- junctival 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 considered later on, has become quite distinct. This embryo had a neck-rump length of 13.6 mm. Fig. 49. — A, Embryo S 2 , 15 mm. Long (showing Ectopia of the Heart) ; B, Embryo L 3 :, 17.5 mm. Long. — {His.) In the embryos xxxv (S 2 ) and xcix (L 3 ) (Fig. 49, A and B) of His' collection the straightening out of the neck bend is proceeding, and indeed is almost completed in embryo xcix, 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 distin- IOO THE DEVELOPMENT OF THE HUMAN BODY. guishable in embryo xxxv and in embryo xcix the eyelids have appeared as slight folds surrounding the conjuncti- val area. The nose and forehead are clearly defined by the greater development of the nasal groove and the nose has also become raised above the general surface of the Fig. 50.— Embryo Wt, 23 mm. Long. — (His.) face, while the external ear has almost acquired its final fetal form. These embryos measure respectively about 15 and 17.5 mm. in length.* * The embryo xxxv presents a slight abnormality in the great pro- jection of the heart, but otherwise it appears to be normal. THE EXTERNAL FORM OF THE BODY. IOI Finally, an embryo — again one of those described by His, namely, his lxxvii (Wt) having a length of 23 mm. — may be figured (Fig. 50) as representing the practical acquisition of the fetal 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 but- tocks. The incompleteness of the development of these regions in embryo lxxvii is manifest, not only from the projection of the tail filament, but also from the ex- ternal genitalia being still largely visible in a side view of the embryo, a condition which will disappear in later stages. The Later Development of the Branchial Arches, and the Development of the Face. — In Coste's embryo (Fig. 46) the four branchial clefts and five arches which develop in the human embryo are visible in surface views, but in the Ruge embryo (Fig. 47) it will be noticed that only the first two arches, the first with a well-developed maxillary pro- cess, 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 depression, the sinus prcecervicalis, is formed on each side of what will later become the anterior part of the neck region. This is well shown in an embryo (Br 3 ) described by His which measured 6.9 mm. in length and of which the anterior por- tion is shown in Fig. 51. 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 102 THE DEVELOPMENT OF THE HUMAN BODY. in later stages these two boundaries gradually approach one another so as first of all to diminish the opening into the sinus and later to completely obliterate it by fusing together, 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 un- 773 Fig. 51. — Head of Embryo of 6.9 mm. na, Nasal pit ; ps, precervical sinus. — (His.) dergoes degeneration, no traces of it occurring normally 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 back- * See page 94, small type. THE DEVELOPMENT OF THE FACE. IO3 ward from the posterior edge of the first arch and fusing with the ventral part of the anterior border of the second arch. The upper part of the second cleft, however, persists, 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. 48 and 49). The region immediately in front of the first arch is /'ip, nasal pit ; os, oral fossa ; pg, processus globularis. — (His.) occupied by a rather deep depression, the oral fossa, whose early development has already been traced. In an em- bryo measuring 8 mm. in length (Fig. 52) the fossa (os) has assumed a somewhat irregular quadrilateral form. Its posterior boundary is formed by the mandibular pro- cesses of the first arch, while laterally it is bounded by the 104 THE DEVELOPMENT OF THE HUMAN BODY. 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 globularis (pg). The ventral ends of the maxillary processes are widely separated, the nasal process and the processus globulares intervening Fig. 53. — Face of Embryo after the Completion of the Upper Jaw. —{His.) between them, and they are also separated from the globu- lar processes by a deep and rather wide groove which anteriorly opens into a circular depression, the nasal pit (np). Later on the maxillary and globular processes unite, THE DEVELOPMENT OF THE FACE. 105 obliterating the groove and cutting off the nasal pits — which have by this time deepened to form the nasal fossae — from direct communication with the mouth, with which, however, they still communicate behind the maxillary processes, an indication of the anterior and posterior nares being thus produced. 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. 53), 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. 48-50. By the narrowing of the nasal process the globular processes are brought nearer together and form the portions of the upper jaw immediately on each side of the median line, the rest of the jaw being formed by the maxillary pro- cesses. In the mean time a furrow has appeared upon the mandibular process, running parallel with its borders (Fig. 49) ; 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 becomes 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 em- bryo measuring about 4 mm. in length (Fig. 45) and are at first bud-like in form. As they increase in length they at first have their long axes directed parallel to the longi- tudinal 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 junc- tion of the flattened and cylindrical portions (Fig. 47), and later a second constriction divides the cylindrical portion 9 106 THE DEVELOPMENT OF THE HUMAN BODY. 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 devel- opment of four radiating shallow grooves upon the hand and foot regions, and a transverse furrow uniting the prox- imal 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 develop- ment 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, which thus come 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. 49 and 50). 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. 47 directed ventrally so that their longitudinal axes are at right angles to that of the 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 the 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 DEVELOPMENT OF THE LIMBS. IO7 The limbs are, however, still in the quadrupedal condi- tion, and they must later undergo a second alteration in position so that 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 shoulders and hip-joints together with a rotation about their longitudi- nal axes through an angle of 90 degrees. This axial rota- tion 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 upon the outer side while the tibial side of the leg is the inner side, and whereas the palmar surface of the hand looks ventrally, the plantar surface of the foot looks dorsally. In making these statements no account is taken of the secondary position which the hand may assume as the result of its pronation; the positions given are those as- sumed 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 physio- logical terms flexor and extensor to describe the surfaces of the limbs has a tendency to obscure their true morphological rela- tionships. 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 move- ments of the lower limb ventrally should be spoken of as move- ments of extension and any movement dorsally as movements of flexion. And yet a ventral movement of the thigh is gener- ally 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. The Age of the Embryo at Different Stages. — The age of an embryo must be dated from the moment of fertilization , and from what has been said in previous pages (pp. 50, 5 1 ) IOS THE DEVELOPMENT OF THE HUMAN BODY. it is evident that it must be exceedingly difficult to deter- mine the exact age of any embryo even when the time of the cessation of the menses and the date of the cohabita- tion which resulted in the pregnancy are known. And, furthermore, not only is the actual date of the beginning of development uncertain, but in the majority of the known human embryos in early stages the time of the cessa- tion of development is also more or less uncertain, since the embryos are abortions and their expulsion need not necessarily have immediately succeeded their death. These various sources of uncertainty are of especial im- portance in the early stages of development, when a day more or less means much. But nevertheless it is conve- nient to have some estimate of the age of such embryos even though it be recognized that any date given is a mere approximation. His has made an estimate of the age of a number of embryos concerning which approximate data were available with results which are stated in the fol- lowing table : M 2-2 i weeks the embryo measures 2.2- 3 mm. in length. " 2J-3 " " " 3 - 4.5 mm. • " " 3J " " " 5-6 mm. " 4 " " " 7 - 8 mm. " " 4J " " " 10 -11 mm. " 5 " " " 13 mm. " It must be borne in mind, however, that embryos of the same age need not in all cases be of the same length, since conditions of nutrition, etc., will largely determine not only the size of the embryo, but also the amount of its development. And, furthermore, it seems probable that the estimates for age given in the above table may be too small, since there is reason to believe that the earlier stages of development proceed more slowly than do the later ones. Tims, Bischoff found that the embryonic disk in THE GROWTH OF THE EMBRYO. IO9 the rabbit showed but little differentiation up to the sev- enth or eighth day, while at the tenth day the embryo possessed branchial clefts and mesodermic somites. It would seem from the available data, which are more definite than usual, that a human embryo described by Eternod and measuring only 1.3 mm. in length was very nearly twenty-one days old ; and if this estimate be correct then the ages assigned by His to the earlier embryos must be very considerably increased. As regards the later periods of development, the limits of error for any date become of less importance. His estimates that at the end of the second month when the embryo becomes a fetus, its length is about 25 to 28 mm., and for later periods Schroder gives the following measure- ments as the average : 3d lunar month, 4th 5th 6th 7th 8th 9th 10th . 70- 90 mm. .100-170 mm. .180-270 mm. .280-340 mm. .350-380 mm. 425 mm. 467 mm. .490-500 mm. The data concerning the weight of embryos of different ages are as yet very insufficient, and it is well known that the weights of new-born children may vary greatly, the authenticated extremes 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 " 120 5th " 285 IIO THE DEVELOPMENT OF THE HUMAN BODY. 6th month, 635 grams. 7th " 1220 " 8th " 1700 9th " 2240 10th " 3250 LITERATURE. J. Broman: " Beobachtung eines menschlichen Embryos von beinahe 3 mm. Lange mit specieller Bemerkung fiber die bei demselben befind- lichenHirnfalten," Morpholog. Arbeiten, v, 1895. J. M. CosTE: "Histoire generate et particuliere du developpement des corps organises," Paris, 1847-1859. A. Ecker: " Beitrage zur Kenntniss der ausserer Eormen jiingster mensch- licher Embryonen," Archiv jiir Anat. und Physiol., Aiiat. Abth., 1880. A. C. F. Eternod: "Communication sur un oeuf humain avec embryon excessivement jeune," Archives Ital. de Biologie, xxn, 1895. A. C. F. Eternod: "II y a un canal notochordal dans 1' embryon humain," Anat. Anzeiger, xvi, 1899. C. Giacomini: "Un ceuf humain de 11 jours," Archives Ital. de Biologie, xxix, 1898. V. HensEn: "Beitrag zur Morphologie der Korperform und des Gehirns des menschlichen Embryos," Archiv jiir Anat. und Physiol., Anat. Abth., 1877. W. His: " Anatomie menschlicher Embryonen," Leipzig, 1880. J. Janosik: "Zwei junge menschliche Embryonen," Archiv jiir mikrosk. Anat., xxx, 1887. F. KEIBEL: "Ein sehr junges menschlicher Ei," Archiv jiir Anat. und Physiol, Anat. Abth., 1890. F. Keibel: " Ueber einen menschlichen Embryo von 6.8 mm. grosster Lange," Verhandl. Anatom. Gesellsch., xiii, 1899. J. Kollmann : " Die Korperform menschlicher normaler und pathologischer Embryonen," Archiv jiir Anat. und Physiol., Anat. Abth., Supple- ment, 1889. F. P. Mall: "A Human Embryo Twenty-six Days Old," Journ. oj Mor- phology, v, 1891. F. P. Mall: "A Human Embryo of the Second Week," Anat. Anzeiger, vm, 1893. F. P. Mall: "Early Human Embryos and the Mode of their Preserva- tion," Bulletin oj the Johns Hopkins Hospital, iv, 1894. C. S. MinoT: "Human Embryology," New York, 1892. J. MullEr: " Zergliederungen menschlicher Embryonen aus friiherer Zeit.," Archiv jiir Anat. und Physiol., 1830. LITERATURE. I I I H. PETERS: " Ueber die Einbettung des menschlichen Eies und das friiheste bisher bekannte menschliche Placentarstadium," Leipzig und Wien, 1899. C. Phisalix: "Etude d'un Embryon humain de 11 millimetres," Archives de zoolog. experimentale et ginirale, Ser. 2, vi, 1888. H. Piper: "Ein menschlicher Embryo von 6.8 mm. Nackenlinie," Archil) jilr Anat. und Physiol., Anat. Abth., 1898. F. Graf von SpEE: "Beobachtungen an einer menschlichen Keimscheibe mit offener Medullarrinne und Canalis neurentericus," Archiv fur Anat. und Physiol., Anat. Abth., 1889. F. Graf von SpEE: "Ueber friihe Entwickelungsstufen des menschlichen Eies," Archiv jilr Anat. und Physiol., Anat. Abth., 1896. 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, in, 1839. (See also Froriep's Neue Notizen, xiii, 1840.) CHAPTER IV. THE MEDULLARY GROOVE, NOTOCHORD, AND MESODERMIC SOMITES. In the youngest human embryos known, such as the Peters' embryo and the youngest embryo described by Graf Spee, there is no differentiation of the embryonic disk other than that associated with the formation of the prim- itive streak. In an embryo described by Eternod and measuring 1.3 mm. in length (Fig. 54) a median longitu- dinal groove (w) has made its appearance, marking out the axis of the disk and forming what is known as the medullary groove; and in the older embryo described by Spee (Fig. 38) a longitudinal ridge has appeared on either side of the groove, forming the medullary folds. The two folds are continuous anteriorly, but behind they are at first separate, the anterior portion of the primi- tive 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-defined blastopore is formed, yet at the time of the formation of the medullary fold an opening breaks through at the anterior end of the primitive streak and places the cavity lying below the endoderm in com- munication with the space bounded by the medullary folds. The canal so formed is termed the neurenteric canal (Fig. 55, nc) and is so called because it unites what will later become the central canal of the nervous system with the intestine (enteron). The significance of this Fig. 54. — Embryo 1.34 mm. Long. al, Allantois; Am, amnion; bs, belly-stalk; h, heart; m, medullary groove ; n.c, neurenteric canal; p.c, caudal protuberance; ps, primitive streak; ys, yolk-stalk. — (Etcrnod.) 10 113 H4 THE DEVELOPMENT OF THE HUMAN BODY. canal is somewhat obscure, and it is of very brief persist- ence, 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. 55. — Diagram of a Longitudinal Section through an Embryo OF 1.54 MM. al, Allantois; am, amnion; B, belly-stalk; ch, chorion; h, heart; uc neurenteric canal; Y, chorionic villi; Y, yolk-sac. — (von Spec.) (Fig. 40) so that their edges finally come into contact and later fuse, the two ectodermal layers forming the one uniting with the corresponding layers of the other (Fig. 56). By this process the medullary groove becomes con- verted into a medullary canal which later becomes the THE MEDULLARY CANAL. 115 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 (Fig. 41) and thence proceeds both anteriorly and posteriorly, the extension of the fusion taking place rather slowly, however, especially anteriorly, so that an anterior open- ing into the otherwise closed canal can be dis- tinguished for a consider- able period (Fig. 42). While these changes have been taking place in the ectoderm of the median line of the em- bryonic disk, modifica- tions of the subjacent en- doderm have also oc- curred. This endoderm, 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 primary endoderm and extending forward as far as what will eventually be the anterior part of the pharynx. Along the line of its junction with the primary endoderm it gives rise to the plates of gastral mesoderm (Fig. 27), while the remainder of it produces an important embryonic organ known as the notochord or chorda dorsalis and on this account is sometimes termed the chorda endoderm, o Fig. 56.- dlagrams showing the Manner of the Closure of the Medullary Groove. n6 THE DEVELOPMENT OF THE HUMAN BODY. After the separation of the plates of gastral mesoderm the chorda endoderm, which is at first a flat band, becomes somewhat curved (Fig. 57, A), so that it is concave on its under surface, and, the curvature increas- ing, the edges of the plate come into contact and finally fuse together (Fig. 57, B), the edges of the primary endo- derm at the same time uniting beneath the chordal tube so formed, so this layer becomes a continuous sheet, as it was at its first appearance. The lumen which is at first Fig. 57. — Transverse Sections through Mole Embryos, showing the Formation of the Notochord. ec, Ectoderm ; en, endoderm ; m, mesoderm ; nc, notochord. — (Heapc.) present in the chordal tube is soon obliterated by the en- largement of the cells which bound it, and these cells later undergo a peculiar transformation 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 med- ullary groove, between the ectoderm and the endoderm, and has on either side of it the mesodermal plates. It is a temporary structure of which only rudiments persist in THE MESO DERMIC SOMITES. I I 7 the adult condition in man, but it is a structure character- istic 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. Turning now to the middle germinal layer, it will be found that in it also important changes take place during these early stages of development. The probable mode of development of the extra-embryonic mesoderm and body-cavity has already been described (p. 84) and atten- tion may now be directed toward what occurs in the em- bryonic 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 becoming continuous at the edges of the embryonic area with both the layer which surrounds the yolk-sac and, through the mesoderm of the belly-stalk, with the chorionic mesoderm (Fig. 35). It seems probable, since there is in these embryos no indica- tion as yet of the formation of the chorda endoderm, that this plate of mesoderm corresponds to the prostomial mesoderm of lower forms. In older embryos, such as the embryo Gle of Graf Spee and the younger embryo de- scribed by Eternod (Fig. 54), the mesoderm no longer forms a continuous sheet extending completely across the embryonic 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. 34). These lateral plates represent the gastral mesoderm, whose origin has already been described (p. 77), and which apparently supplants the original prostomial mesoderm, whose fate in the human embryo is I iS THE DEVELOPMENT OF THE HUMAN BODY. at present unknown. The changes which now occur have not as yet been observed in the human embryo, though they probably resemble those described in other mamma- lian embryos, and the phenomena which occur in the sheep may serve to illustrate their probable nature. The lateral plates increase in size by the multiplication of the cells which compose them and, in sections, have a somewhat triangular form, the portions nearest the me- dian line of the embryo being much thicker than the more lateral parts. In the region which will later become the Fig. 58. — Transverse Section through the Second Mesodermic Somite of a 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.) neck of the embryo a longitudinal groove appears upon the dorsal surface of each plate, marking off the more median thicker portion from the lateral parts, and the median portions then become divided transversely into a number of more or less cubical masses which are termed the protovertebrce or, better, mesodermic somites (Fig. 58, ms), structures whose appearance in surface views has already been described (Figs. 4.1 et seq.). The cells of the somites and of the lateral parts, which may be termed the THE MESODERMIC SOMITES. II9 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. 58). The cavities of the somites first formed become continuous with the cavities contained between the layers of the adjacent ventral mesoderm, but this continuity eventually disappears and Fig. 59. — Transverse Section of an Embryo of 2.5 mm. (See Fig. 42) showing on either side of the medullary canal a mesodermic Somite, the Intermediate Cell-mass, and the Ventral Meso- derm. — (von Lenhossek.) is not developed in the later formed somites. Each origi- nal lateral plate of gastral mesoderm then becomes divided longitudinally into three areas, a more median area com- posed 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 120 THE DEVELOPMENT OF THE HUMAN BODY. mass (Fig. 58, i), and, finally, the ventral mesoderm. This last portion is now divided into two layers, the dorsal of which is termed the somatic mesoderm, while the ventral one is known as the splanchnic mesoderm (Fig. 58, so and sp; and Fig. 59), the cavity which separates these two layers being the embryonic body-cavity or pleuroperito- neal cavity, 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. Beginning in the neck region, the formation of the mesodermic somites proceeds anteriorly and 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 with mesodermic somites. Whether this homology be perfectly correct or not, these head-cavities, as they are termed, indicate the existence 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. 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, as has already been stated, the somite cavity is at first continuous with the THE MESO DERMIC SOMITES. 121 pleuroperitoneal cavity and only later becomes separated off 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 /"A. ■■>,* ^» -M B-m, '>.'..'•' _* « ' ' ''.' ''Stf "• ' si x^!7)i JRJ Iff ^fe^~ -V« i?S5& -rags Fig. 60. — 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, myotome; me, splanchnic mesoderm; ol, outer lamella of myo- tome ; Pn, place of origin of pronephros; S, sclerotome ; S 1 , defect in wall of myotome due to separation of the sclerotome ; st, stomach ; Vu, umbilical vein. — {Kolhnann.) 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 122 THE DEVELOPMENT OF THE HUMAN BODY. themselves undergo a differentiation into distinct por- tions. The cells of that portion 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 event- ually 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. 60, s), and the remaining part of the medial wall forms a muscle plate or myotome (to) which is destined to give rise to a portion of the voluntary musculature of the body, while the outer wall probably takes part in the formation of the cutis layer of the skin and hence has been termed the cutis plate, or dermatome. 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 of most of the somites (Fig. 60, pn) the provisional kidneys or Wolffian 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 con- stituting that form of mesoderm which has been termed mesenchyme (see p. 80). 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 corre- sponding to the mesodermic somites, differing in this respect from the other portions of the gastral 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 with the development of the branchial arches and clefts. A THE VENTRAL MESODERM. I 23 consideration of these segments, which are known as the branchiomeres, 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 splanchnic layer applies itself closely to the endo- dermal digestive tract (Fig. 62, sp), 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 arrange- ment 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, become col- umnar in shape and are converted into reproductive cells. The somatic layer, if traced peripherally, becomes con- tinuous at the sides with the layer of mesoderm whichlines the outer surface of the amnion (Fig. 60) 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 differen- tiated 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. 61). 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 124 THE DEVELOPMENT OF THE HUMAN BODY. buds to form an axial core for them (Fig. 61 , Lr), in which later the skeleton of the limb forms. The remainder 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 into itself, the membrana reuniens until finally the latter has completely disappeared. It is to be noted that no part of the voluntary muscula- ture of the lateral and ventral walls of the neck and trunk is derived from the somatic layer, nor do the muscles of the limbs arise from the axial core of mesenchyme which passes into them from this layer.* All the voluntary muscles of the neck, trunk, and limbs are derived from the myotomes which gradually extend ventrally and send out also into the limbs prolongations which completely in- vest the axial mesenchyme, and it is probable, also, that the ribs are derived from ventral prolongations of the sclerotomes. The probable relations of the various parts derived from the gastral mesoderm may be perceived from the diagrams composing Fig. 61, which represent the conditions obtaining in embryos of different ages. The appearance of the mesodermic somites is an im- portant phenomenon in the development of the embryo, since it influences fundamentally the future structure of the organism. If each pair of mesodermic somites be regarded as an element and termed a metamere or seg- ment, then it may be said that the body is composed of a series of metameres, each more or less closely resembling its fellows, and succeeding one another at regular inter- vals. Each somite differentiates, as has been stated, into a sclerotome, a myotome, and a cutis plate, and, accord- * See page 231. METAMERISM. 125 ingly, there will primarily be as many vertebrae, muscle segments, and cutis segments as there are mesodermic somites, or, in other words, the axial skeleton, the volun- tary muscles, and the cutis are primarily metameric. Nor is this all. Since each metamere is a distinct unit, it must possess its own supply of nutrition, and hence the primary arrangement of the blood-vessels is also metameric, a MQ Fig. 61. — Diagrams Illustrating the History of the Gastral Mesoderm. C, Cutis plate; Dm, dorsal portion of myotome; Gr, genital ridge: /, in- testine; Lr, limb bud; Mr, membrana reuniens ; N, nervous system ; " Nc, notochord; Sc, sclerotome; So and Sp, somatic and splanchnic mesoderm; Vm, ventral portion of myotome; Wd, Wolffian duct. — (Modified from Kallmann.) branch passing off on either side from the main longitu- dinal arteries and veins to each metamere. And, further, each pair of muscle segments and the corresponding cutis plates receive their own nerves, so that the arrangement of the nerves, again, is distinctly metameric. This metamerism is most distinct in the neck and trunk regions, and at first only in the dorsal portions of these 126 THE DEVELOPMENT OF THE HUMAN BODY. 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 this, like the rest of the body, is to be regarded as composed of metameres. It has been seen that in the notochordal region of the head of lower verte- brates mesodermic somites are present, while anteriorly in the praechordal region there are head-cavities which resemble the mesodermic somites in that their walls be- come converted into muscle tissue, and which may, per- haps, be directly comparable to the somites of the trunk. There is reason, therefore, for believing that the funda- mental arrangement of all parts of the body is metameric, but though this arrangement is clearly defined in early embryos, it loses distinctness in later periods of develop- ment. The various cutis metameres early unite, so that their primary relations become greatly obscured, and the same is true to a certain extent of the muscle segments and of the blood-vessels; but even in the adult the pri- mary metamerism is clearly indicated in the arrangement of the nerves and of parts of the axial skeleton, and careful study frequently reveals indications of it in highly modi- fied 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 prevails 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 branchio- meres cannot be regarded as portions of the head meta- LITERATURE. 1 2J meres or even structures comparable to these. They represent, more probably, a second metamerism super- posed 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 (see p. 431). LITERATURE. In addition to many of the papers cited in the list at the close of Chapter II, the following may be mentioned: W. HeapE: "The Development of the Mole (Talpa Europsea)," Quarterly Journ. Microsc. Science, xxvn, 1887. F. KeibEL: "Zur Entwickelungsgeschichte der Chorda bei Saugern (Meer- schweinchen und Kaninchen)," Archill fur Anat. und Physiol., Anat Abth., 1889. J. Koiamann: "Die Rumpfsegmente menschlicher Embryonen von 13 bis 35 Urwirbeln," Archiv fur Anat. und Physiol., Anat. Abth., 1891. J. W. van Wijhe: "Ueber die Mesodermsegmente des Rumpfes und die Entwicklung des Excretionsystems bei Selachiern," Archiv fur mi- krosk. Anat., xxxm, 1889. K. W. ZimmERMAnn: "Ueber Kopfhohlenrudimente beim Menschen,'' Archiv fur mikrosk. Anat., un, 1898. 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 differ- ent from those under which the adult organisms exist that in the early stages of development special organs are very frequently developed which are of use only during the embryonic or larval period and are discarded when more advanced stages of development have been reached. This remark applies with especial force to the human em- bryo 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, becomes greatly modified, the combination of embryonic and maternal structures producing what is termed the deciduce, owing to its being discarded at birth when the parasitic mode of life is given up. Furthermore, it has already been seen that many pecu- liar 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 modi- fied condition organs of considerable functional impor- tance in lower forms. Such structures are the yolk-stalk 128 THE AMNION. 129 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 constricted off from the surface of the large yolk-mass, a fold, consisting of ectoderm and somatic mesoderm, arises just outside the embryonic area, which it completely sur- Fig. 62. — Diagrams Illustrating the Formation of the Amnicn and Allantois in the Chick. Af, Amnion folds; Al, allantois; Am, amniotic cavity; Ds, yolk-sac. — (Gegenbaur.) rounds. As development proceeds the fold becomes higher and its edges gradually draw nearer together over the dorsal surface of the embryo (Fig. 62, A), and finally meet and fuse (Fig. 62, B), so that the embryo becomes enclosed within a sac, which is termed the amnion and is formed by the fusion of the layers which constituted the inner wall of the fold. The layers of the outer wall of the 130 THE DEVELOPMENT OF THE HUMAN BODY. fold after fusion form part of the general ectoderm and somatic 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 amnion and the serosa is a por- tion 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 protoplasmic material is limited to one pole and rests upon the large yolk-mass. As development proceeds the germ layers gradually extend around the yolk-mass (compare Fig. 62, A-C) and eventually completely enclose it, the yolk-mass coming to lie within the endodermal layer, which, together with the splanchnic mesoderm which lines it, forms what is termed the yolk-sac. As the em- bryo separates from the yolk-mass the yolk-sac is con- stricted 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 mean time, 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. 62, A). This increases in size, projecting into the extra- embryonic portion of the pleuroperitoneal cavity and pushing before it the splanchnic mesoderm which lines the endoderm (Fig. 62, B and C). This is the allantois, which, reaching a very considerable size in the chick, and apply- ing itself closely to the inside of the serosa, serves as a respiratory 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 am- THE AMNION. I3I nion and allantois begin to undergo retrogressive changes-, and just before the hatching of the young chick they be- come 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 struc- tures. 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 some- what degenerated condition. It has been seen from the description of the earliest stages of development that the processes which occur in the lower forms are greatly abbre- viated in the human embryo. The enveloping layer, instead of gradually extending from one pole to enclose the entire ovum, develops in situ during the stages imme- diately succeeding segmentation, and the extra-embry- onic mesoderm, instead of growing out from the embryo to ejticlose the yolk-sac, splits off directly from the envel- oping layer. 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. 35) and in the embryo v.H. of von Spee (Fig. 37) 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 described as occurring in the bat (p. 71). It is, then, a closed cavity from the very beginning, the floor of the cavity 132 THE DEVELOPMENT OF THE HUMAN BODY. 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 meso- Fig. 63. — Diagrams Illustrating the Formation of the Umbilical Cord. Tlie heavy black line represents the embryonic ectoderm; the dotted line represents the line of reflexion of the body ectoderm into that of the amnion. Ac, Amniotic cavity; Al, allantois; Be, extra-embry- onic coelom ; Bs, belly-stalk ; Ch, chorion ; P, placenta ; Uc, umbilical cord ; V , chorionic villi ; Ys, yolk-sac. derm continuous with the somatic mesoderm of the em- bryo and the mesoderm of the belly-stalk (Fig. 63, A). When the bending downward of the peripheral portions of the embryonic disk to close in the ventral surface of the THE AMNION. I 33 embryo occurs, the line of attachment of the amnion to the disk is also carried ventrally (Fig. 63, 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 considered the posterior surface of the belly-stalk, while at the sides it is attached along an oblique line joining these two points (Figs. 63, 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. 139), it may be said that during the later growth of the embryo the amniotic cavity increases in size until finally its wall comes into contact with the chorion, the extra- embryonic body-cavity being thus practically obliterated (Fig. 63, D), though no actual fusion of amnion and cho- rion occurs. Suspended by the umbilical cord, 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 infiltrates into the cavity from the maternal tissues, while others hold that a certain amount of it at least is derived from the embryo. It is a fluid with a specific gravity of about 1 .003 and contains about 1 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 \ and f of a liter, but during the last month it diminishes to about half that quantity. To protect the epidermis of the fetus from maceration during its prolonged immersion in the liquor amnii, the sebaceous glands of the skin at about the sixth month of develop- I 34 THE DEVELOPMENT OF THE HUMAN BODY. ment 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 result 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 extensive to allow the pas- sage of the child, the amnion remaining behind in the uterus, to be subsequently expelled along with the de- cidual. Occasionally it happens, however, that the amnion is suffi- ciently strong to withstand the pressure exerted upon it by the uterine contractions 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 super- stition, 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 quantities, producing a condition known as hydramnios. On the other hand, the amount may fall con- siderably below the normal, in which case the amnion may form abnormal unions with the embryo, sometimes producing malformations. Occasionally also bands of a fibrous char- acter traverse the amniotic cavity and, tightening upon the embryo during its growth, may produce various malformations, such as scars, splitting of the eyelids or lips, or even amputa- tion of a limb. The Yolk=sac. — The development of the yolk-sac in the human embryo, its differentiation into yolk-stalk and yolk-vesicle, and its enclosure within the umbilical cord have already been described. When 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. 63, D), and the stalk is a long slender column of cells extending from the vesicle through the umbilical cord to unite with the intestinal tract of the embryo. The THE YOLK-SAC. I 35 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 under- goes degeneration, the lumen which it at first contains 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 dis- appears, but in about 3 per cent, of cases it persists, form- ing 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 100 cases of occlusion of the small intestine 6 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 absorp- tion, of the yolk is carried on, and even although the func- tional 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 espe- cially possessing a rich network of vessels. The future history of these vessels, which are known as the omphalo- mesenteric 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. I36 THE DEVELOPMENT OF THE HUMAN BODY. In man it subserves similar functions, but is very much modified both in its mode of development and in its rela- tions 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 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 intestine has differentiated from the yolk-sac and pushes its way into the solid mass of mesoderm which forms the belly-stalk (Fig. 63, A). To understand the significance of this process it is necessary to recall the abbreviation in the human embryo of the development of the extra-em- bryonic mesoderm and body-cavity. Instead of growing out from the embryonic area, as it does in the lower forms, this mesoderm develops in situ by splitting off from the layer of enveloping cells and, furthermore, the extra- embryonic body-cavity arises by a splitting of the meso- derm so formed before there is any trace of a splitting of the embryonic mesoderm (Figs. 36 and 35). The belly- stalk, whose development from a portion of the inner cell- mass has already been traced (p. 85), is to be regarded as a portion of the body of the embryo, since the ectoderm which covers one surface of it resembles exactly that of the embryonic disk and shows an extension backward of the medullary groove upon its surface (Fig. 64). The meso- derm, therefore, of the belly-stalk is to be regarded as a portion of the embryonic mesoderm which has not yet THE ALLANTOIS. 137 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 endodermal allan- toic 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 mammals, the endodermal portion of the allan- tois 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 mammals as the marsupials, the rabbit, and the ruminants. In man, however, the endodermal diverticulum never becomes a sac-like struc- ture, but is a slender tube ex- tending from the intestine to the chorion and lying in the sub- stance of the mesoderm of the belly-stalk (Fig. 63, 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 explanation 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 res- piration 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 ovip- arous mammals there are no means by which excreted ^Ul Fig. 64. — Transverse Sec- tion THROUGH THE BEIAY- STALK OF AN EMBRYO OP 2.15 MM. Aa; Umbilical (allantoic) ar- tery; All, allantois; 'am, amnion; Va, umbilical (al- lantoic) vein. — (his.) I38 THE DEVELOPMENT OF THE HUMAN BODY. 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, indicating 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 arrangement for the passage of the excreted material into the maternal blood being so perfect that there is practically no need for the develop- ment 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-embry- onic portions of the allantois reach a greater development, the more proximal portions acquiring a cavity of consid- erable extent and forming the urogenital sinus and the urinary bladder, while the portion intervening between the apex of the bladder and the umbilicus becomes con- verted 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. Since the allantois in the human embryo, as well as in the lower forms, is responsible for respiration and excre- tion, its blood-vessels are well developed. They are repre- sented in the belly-stalk by two veins and two arteries (Fig. 64), known in human embryology as the umbilical THE UMBILICAL CORD. I 39 veins and arteries, which 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. 63, B). At the edges of this area in front and at the sides the embryonic 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. 63 B), so that the whole of the ventral surface of the stalk is entirely uncovered by ectoderm, this layer being limited to its dorsal surface (Fig. 64). 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 extending more laterally, the condition represented in Fig. 63, 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 sur- face of the body to the chorion and forming the umbilical cord (Fig. 63, D). From this mode of development it is evident that the cord is, strictly speaking, a portion of the embryo, its sur- faces 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. I40 THE DEVELOPMENT OF THE HUMAN BODY. d : m0 al V / V -iC *-y—7 "v;.:. ^nJ| -uv -ua -yr UV Fig. 65. — Transverse Sections of the Umbilical Cord of Embryos of (a) 1.8 cm. and (b) 25 cm. al, Allantois; c, coelom; ua, umbilical artery; uv, umbilical vein; ys yolk-stalk. THE UMBILICAL CORD. 141 In enclosing the yolk-stalk the umbilical cord encloses also a small portion of what was originally the extra- embryonic body-cavity surrounding the yolk-stalk. A section of the cord in an early stage of its development (Fig. 65, 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 sur- face 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 be- comes 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 en- croached 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 arteries and vein, the allantois, and the rudiments of the yolk-stalk (Fig. 65, B). When fully formed, the umbilical cord measures on the average 55 cm. in length, though it varies considerably in different cases, and has a diameter of about 1.5 cm. It presents the appearance 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 move- ments of the embryo in the later stages of development and may even be knotted. The greater part of its substance 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. 142 THE DEVELOPMENT OF THE HUMAN BODY. The Chorion.— The umbilical cord, or, more properly, the belly-stalk, places the body of the embryo in commu- nication with the wall of the embryonic vesicle, and this wall, termed the chorion, is in contact with the walls of the uterus and becomes specially modified to produce the con- nection between the embryo and the maternal tissues which is characteristic of all the higher mammalia. It is composed of two layers, an outer ectodermal trophoblast layer and an inner chorionic mesoderm. In the earliest stages it may be presumed that the trophoblast is com- Fig. 66. — Two Diagrams Illustrating the Formation of Chorionic Villi. Bl, Blood-space ; ca, maternal capillary ; en, endothelium ; fi, fibrin ; Is, intervillous space ; M, chorionic mesoderm ; sp, stratum spon- giosum; Sy, syncytium; TV, trophoblast; v, villus. — (Peters.) paratively thin, as in the bat's ovum, and later becomes a stout layer many cells thick. In the Peters embryo, whose ovum measures only about i mm. in diameter, it has already become quite thick and contains numerous blood lacunas arranged as a network throughout its sub- stance. These lacunae seem to have been produced by blood extravasated from the maternal vessels penetrating into the substance of the trophoblast and breaking it up into irregular bands and processes (Fig. 66, A), this being possible from the fact that even at this early stage the THE CHORION. '43 ovum is completely embedded in the mucosa of the uterus. In later stages the lacunae increase in size and unite to form an extensive blood space completely sur- rounding the embryonic vesicle. Into this blood space the vessels of the uterine walls open, and into it also the irregular processes of the trophoblast project, forming what are termed the chorionic villi, the space itself being known as the intervillous space (Fig. 66, B). ON Fig. 67. — Two Villi from the Chorion op an Embryo op 7 mm. These villi may at first be developed over the whole surface of the chorion or they may be limited to a broad band situated at what may be termed the equator of the ovum; but whichever arrangement occurs, only those de- veloped from that portion of the chorion to which the belly-stalk is attached undergo further elaboration in later stages, the rest gradually disappearing or remaining only as minute rudiments. It is customary, consequently, 144 THE DEVELOPMENT OF THE HUMAN BODY. Fig. 68. — Transverse Sections through Chorionic Villi in (A) the Fifth and (B) the Seventh Month of Development. cj, Canalized fibrin; Ic, Langhans cells; s, syncytium. — (A, which is more highly magnified than B, from Szymonowicz; B from Minot.) THE CHORION. 145 to speak of that portion of the chorion in which the de- velopment of the villi proceeds as the chorion frondosum, to distinguish it from the remaining portion, which is termed the chorion Iceve. The villi (Fig. 67) at first are irregularly lobed processes formed by a solid mass of tro'phoblast cells and projecting fully into the intervillous space, a lobe here and there extending completely across the space (Fig. 76) and unit- ing with the maternal tissues to form roots of attachment. As development proceeds the lobes become much more slender and branch so that each villus assumes a dendritic form. In the mean time, however, processes from the chorionic mesoderm grow out into each villus, extending out even into the terminal branches and forming a central core in which blood-vessels develop, which become con- tinuous with the umbilical arteries and veins. When this has occurred, the ectoderm differentiates into two layers, a superficial one in which the cell-boundaries disappear so that it consists of a continuous layer of protoplasm in which numerous nuclei are embedded (Fig. 68, A, s) and which is termed the syncytium, and an inner one, consist- ing of well-defined cells arranged in a single layer and termed the Langhans cells (Ic). It may be stated that the exact significance of these two layers is still under discussion, some authors believing the Langhans cells to be mesodermal, while others, admitting that they are ectodermal, maintain the view that the syn- cytium is really maternal tissue. The view here presented is most in accord with the more recent observations (Minot, Peters). As development proceeds the villi, which are at first distributed evenly over the chorion frondosum, are separated into groups termed cotyledons (Fig. 69), by the growth into the intervillous space of trabecules from 146 THE DEVELOPMENT OF THE HUMAN BODY. the walls of the uterus, the villous roots of attachment becoming connected with these septa as well as with the general uterine wall. The ectoderm of the villi also undergoes certain changes with advancing growth, the layer of L,anghans cells disappearing except in small areas scattered irregularly in the villi, and the syncytium, though persisting, undergoes local thickenings which de- generate more or less extensively into fibrin-like sub- stance"(Fig. 68, B, cf). Fig. 69. — Mature Placenta after Separation from the Uterus. c, Cotyledons; ch, chorion, amnion, and decidua vera; um, umbilical cord. — (Kollmann.) The changes which occur during the later stages of development in the chorion are very similar to those de- scribed for the villi. Thus, the mesoderm thickens, its outermost layers becoming exceedingly fibrillar in struc- ture, while the ectoderm differentiates into two layers, the outer of which is syncytial while the inner is cellular, and later still, as in the villi, the syncytial layer degener- ates in irregular patches into a peculiar form of fibrin THE DEClDU.lt. H7 which is traversed by flattened anastomosing spaces and to which Minot has applied the name canalized fibrin (Fig. 70). The Deciduae. — In connection with the phenomenon of ,*■&&?■'■■ ■*<&>■ ,.*&& mes Fig. 70. — Section through the Placentae Chorion of an Embryo of Seven Months. c, Cell layer ; ep, remnants of epithelium ; fb, fibrin layer ; mes, meso- derm. — (Minot.) menstruation periodic alterations occur in the mucous membrane of the uterus. If during one of these periods a fertilized ovum reaches the uterus, the desquamation of I48 THE DEVELOPMENT OF THE HUMAN BODY. portions of the epithelium 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 condition until the conclusion of pregnancy, when, after the birth of the fetus, a considerable portion of its thickness is expelled from the uterus, forming what is Fig. 7 1 . — Diagram showing the Relations of the Fetal Membranes. Am, Amnion; Ch, chorion; M, muscular wall of uterus; R, decidua reflexa ; S, decidua serotina ; V, decidua vera ; Y, yolk-stalk. termed the deciduce. In other words, the sloughing of the uterine mucosa which concludes the process of menstrua- tion 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 mucosa are somewhat more extensive during pregnancy than during THE DECIDU.E. 149 menstruation, but there is an undoubted fundamental similarity in the changes during the two processes. 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 occurring elsewhere. Consequently it becomes Fig. 72. — 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, papillae; rf, marginal furrow. — (Kolhnann.) possible to divide the deciduae into (1) a portion which is not in direct contact with the ovum, the decidua vera (Fig. 71, V) and (2) a portion which is. The latter portion is again capable of division. The ovum becomes com- pletely embedded in the mucosa, but, as has been pointed ISO THE DEVELOPMENT OF THE HUMAN BODY. out, the chorionic villi reach their full development only over that portion of the chorion to which the belly-stalk is attached. The decidua which is in relation to this chorion frondosum undergoes much more extensive modi- fications than that in relation to the chorion lasve, and to it the name of decidua serotina (Fig. 71, S) is applied, while the rest of the decidua which encloses the ovum is termed the decidua reflexa (R). 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 de- cidua vera is at the height of its de- velopment, the surface of the mucosa presents a corrugated appearance and 4ig§ Fig. 73. — 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 Engelmann.) is traversed by irregular and rather deep grooves (Fig. 72). This appearance ceases at the internal os, the mu- cous membrane of the cervix uteri not forming: a de- THE DEC1DLLE. IJI cidua, and the decidual 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 measuring i cm. in thickness, and its glands have undergone very considerable modification. Normally almost straight (Fig. 73, A), they increase in length, not only keeping 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. 73, B). Near their mouths they are dilated, but not very much contorted, while lower down the re- verse is the case, and it is possible to recognize three layers in the decidua, (1 ) 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 muscular 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 col- umnar form, elsewhere it becomes more or less flattened and shows a tendency toward degeneration. 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 stra- tum compactum becomes packed with large, often multi- nucleated cells, which are termed the decidual cells. 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 thick- ness. The portions of the glands which lie in the stratum compactum become more and more compressed and 152 THE DEVELOPMENT OF THE HUMAN BODY. finally disappear, while in the spongiosum the spaces be- come much flattened and the vascularity of the whole decidua, at first so pronounced, diminishes greatly. (b) Decidua reflexa. — The decidua reflexa receives its name from the fact that it was supposed to arise as a fold of the mucous membrane of the uterus and to be reflected Fig. 74. — Section op an Ovum of 1 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 Strahl, after Peters.) over the ovum after this had attached itself. Recent observations, however, throw doubt on this mode of origin. Thus, the ovum described by Peters (Fig. 74) was already almost completely enclosed by the reflexa, a small area at one pole being alone exposed. The uterine epithe- THE DECIDILE. I 53 Hum around the margins of this unenclosed area was exceedingly thin and had the appearance of being stretched by the growth of the ovum. Peters interprets the condition found in this very early stage by supposing that when the ovum reached the uterus it came into con- tact with the thickened mucosa at a point where the epithelium had been thrown off and at once proceeded to embed itself in the substance of the mucosa. By the time it reached a diameter of about i mm. the ovum was almost completely embedded and the mucosa sur- rounding it constituted the reflexa. According to this view, which seems to be more in harmony with what has been observed, there is no formation of a fold and no re- flection over the surface of the ovum, but the reflexa is due to the ovum becoming embedded in the substance of the mucosa. As development proceeds the reflexa eventually com- pletely encloses the ovum, the point of union of the edges of the aperture through which the ovum sank into the mucosa being indicated for some time by a scar-like mark. The general structure of the reflexa is closely similar to that described for the vera, but as the ovum increases in size it becomes thinner and thinner, and at about the fifth month has come into contact with the vera, forming a whitish transparent membrane with no traces of either glands or blood-vessels, and very possibly it eventually degenerates and completely disappears (Minot). (c) Decidua serotina. — The structure of the serotina up to about the fifth month of development is practically the same as that of the vera. It loses its epithelium very early, probably before the attachment of the ovum, and the glands undergo the same changes as in the vera, so that the compactum and spongiosum can be recognized. Beyond the fifth month, however, there is a great differ- 13 Mc 154 THE PLACENTA. I 55 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 decidual, but persists until birth, forming a part of the structure termed the placenta. The Placenta. — This organ, which forms the connection between 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 serotina. Hence the terms placenta faetalis and placenta uterina frequently applied to the two parts. The fully formed placenta is a more or less dis- coidal structure, convex on the surface next the uterine muscularis and concave on that turned toward the em- bryo, 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 be- tween 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 os. It develops, in fact, wherever the ovum happens to become attached to the uterine walls, and oc- casionally this attachment is not accomplished until the ovum has descended nearly to the internal os, in which case the placenta may completely close this opening and form what is termed a placenta prcevia. If a section of a placenta in a somewhat advanced stage of development be made, the following structures may be Fig. 75. — Section through a Placenta of Seven Months' Develop- ment. Am, Amnion; cho, chorion; D, layer of decidua containing the uterine glands ; Mc, muscular coat of the uterus ; Ve, maternal blood-vessel ; Vi, stalk of a villus; id, villi in section. — (Minot.) I 56 THE DEVELOPMENT OF THE HUMAN BODY. distinguished: On the inner surface there will be a deli- cate layer representing the amnion (Fig. 75, Am), and next to this a somewhat thicker one which is the chorion (cho), in which the degenerative changes already men- tioned may be observed. Succeeding this comes a much broader area composed of the large intervillous blood space in which lie sections of the villi (yi) cut in various directions. Then follows the stratum compactum of the serotina, next the stratum spongiosum, next the outer- most layer of the mucosa (D"), in which the uterine glands retain their epithelium, and, finally, the muscularis uteri (Mc). These various structures which enter into the composi- tion of the placenta have, for the most part, been already described, and it remains here only to say a few words con- cerning the special structure of the serotinal compactum and concerning the origin of the intervillous space and its relations to the villi and the maternal vessels. From the surface of the compactum processes arise, termed septa, which project into the intervillous space, grouping the villi into cotyledons and giving fixation to some of the roots of attachment of the villi (Fig. 75). Throughout the greater extent of the placenta the septa do not reach the surface of the chorion, but at the periph- ery, throughout a narrow zone, they do come into con- tact with the chorion and unite beneath it to form a mem- brane which has been termed the closing plate. Beneath this lies the peripheral portion of the intervillous space, which, owing 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. 76). The probable origin of the intervillous space by the effusion of blood from the maternal vessels into the sub- Is a a O „ .- H « a ■sis o ►« B 5 ££ w a H H < S3 w o <: j PL, < 2 w M a M ^~ in a" s e a § o 3~ a^ 5 &"§ ".at •- H 2 a w .- rt O 53 S « a ^3 is n a ci 2 . - o Tll Si Li Ls Fig. 78. — Diagram showing the Cutaneous Distribution of the Spinal Nerves. — {Head.) St 164 THE DEVELOPMENT OF THE HUMAN BODY. more or less distinct zones, and being therefore segmented (Pig. 78). But a considerable commingling of adjacent dermatomes has also occurred. Thus, while the distribution of the cutaneous branches of the fourth thoracic nerve, as determined experimentally in the monkey (Macacus), is dis- tinctly 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. 79), so that any area of skin in the zone is innervated by fibers coming from at least two segmental nerves (Sherrington). And, furthermore, the distribution 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 dermatomes but a dermatome may shift its position relatively to the Fig. 79. — Diagram showing the Overlap of the III, IV, and V Inter- costal NERVES op a Monkey. — (Sherrington.) deeper structure supplied by the same nerve, so that the skin over a certain muscle is not necessarily supplied by fibers from the nerve which supplies the muscle. Thus, in the lower half of the abdomen, the skin at any point will be sup- plied 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 nails have been described by Zander in embryos of about nine weeks as slight thicken- THE NAILS. I6 5 ings of the epidermis of the tips of the digits, these thick- enings being separated from the neighboring tissue by a faint groove. Later the nail areas migrate to the dorsal surfaces of the terminal phalanges (Fig. 80) and the grooves surrounding the areas deepen, especially at their proximal edges, where they form the nail-folds (w/), while distally thickenings of the epidermis occur to form what have been termed sole-plates (sp), structures quite rudi- Fig. 80. — Longitudinal Section through the Terminal Joint op the Index-finger of an Embryo of 4.5 CM. e, Epidermis; ep, epitrichium ; nf, nail fold; Ph, terminal phalanx; sp, sole plate. mentary in man, but largely developed in the lower ani- mals, 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 1 7 cm. By this time the epidermis has become several layers thick and its outer layers, over the nail areas as well as elsewhere, have 1 66 THE DEVELOPMENT OF THE HUMAN BODY. •S0-! sc ep- fi become transformed into the stratum corneum (Fig. 81, sc), and it is in the deeper layers of this that keratin gran- ules develop in cells which degen- erate to give rise to the nail sub- stance (n). At its first formation, accordingly, the nail is covered by the outer layers of the stratum corneum as well as by the epitri- chium, the two together forming what has been termed the epony- chium (Fig. 81, ep). The epitri- chium soon disappears, however, leaving only the outer layers of the stratum corneum as a covering, and this also later disappears with the exception of a narrow band sur- rounding 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. Fig. 81. — Longitudinal Section through the Nail Area in an Em- bryo of 17 CM. ep, Eponychium; «, nail substance ; nb, nail bed ; sc, stratum corneum; sp, sole plate. — (Oka- mum ) The first appearance of the nail areas at the tips of the digits as described by Zander has not yet been con- firmed by later observers, but the mi- gration of the areas to the dorsal sur- face necessitated by such a location of the primary differentiation affords THE HAIR. 167 an explanation of the otherwise anomalous cutaneous nerve- supply of the nail areas in the adult, this being from the palmar (plantar) nerves. 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 life. They Fig. 82. — The Development of a Hair. c, Cylindrical cells of stratum mucosutn; kj, wall of hair follicle; m, mesoderm ; tnu, stratum mucosum of epidermis ; p, hair papilla ; r, root of hair; s, sebaceous gland. — {Kallmann.) arise as solid cylindrical downgrowths, projecting ob- liquely into the subjacent dermis from the lower surface of the epidermis. As these downgrowths continue to elongate, they assume a somewhat club-shaped form (Fig. 82), and later the extremity of each club moulds itself 1 68 THE DEVELOPMENT OF THE HUMAN BODY. over the summit of a small papilla which develops from the dermis (Fig. 82). Even before the dermal papilla has made its appearance, however, a differentiation of the cells of the downgrowth becomes evident, the central cells becoming at first spindle-shaped and then undergo- ing a keratinization to form the hair shaft, while the more peripheral ones assume a cuboidal form and 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 by the multipli- cation of the epidermal cells which envelop the papilla. From the cells which form the lining of each follicle an outgrowth takes place into the surrounding dermis to form a sebaceous 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 genera- tions 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, connected with the hair follicles arise from the mesenchyme cells of the surrounding dermis. The first growth of hairs 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 THE SUDORIPAROUS GLANDS. 169 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 continually 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 replac- ing hair arises from a pa- pilla which is probably budded off from the older one before its degenera- tion and carries with it a cap of epidermal cells. — h Fig. 83. — Lower Surface op a De- tached Portion of Epidermis from the Dorsum of the Hand. h, Hair follicle ; s, sudoriparous gland. — (Blasckko.) It is uncertain whether the cases of excessive de- velopment of hair over the face and upper part of the body which occasionally occur are due to an ex- cessive development of the later hair follicles (hypertrichosis) or to a persistence and con- tinued growth of the lanugo. The Development of the Sudoriparous Glands. — The sudoriparous glands arise during the fifth month as solid cylindrical outgrowths from the primary ridges of the epi- dermis (Fig. 83), 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, how- ever, the cylinders are formed from the deeper layers of the epidermis, their lumina do not at first open upon the 170 THE DEVELOPMENT OF THE HUMAN BODY. 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 majority 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 epi- dermis along a line situated at the junction of the abdominal walls with the membrana re- uniens (Schulze). This thickening subsequent- ly becomes a pro- nounced ridge, the milk ridge, from which at certain points the mammary glands de- velop, the ridge disap- pearing in the inter- vals. In a human embryo 4 mm. in length an epidermal thickening has been observed which extended from just below the axilla to the inguinal region (Fig. 84) and was apparently equivalent to the milk line of the pig, and in embryos of 14 or 15 mm. the upper end of the line had become a pronounced ridge, while more posteriorly the thickening had disappeared. The further history of the ridge has not, however, been yet traced in human embryos, and the next stage of the development of the glands which has been observed is one Fig. 84. — Milk Ridge (mr) in a Human Embryo. — (Kallius.) THE MAMMARY GLANDS. I 7 I in which they are represented by a circular thickening of the epidermis which projects downward into the dermis (Fig. 85, A). Later the thickening becomes lobed (Fig. 85, B), and its superficial and central cells become corni- fied and are cast off, so that the gland area appears as a depression of the surface of the skin. During the fifth and ., 9 ov; • ' -\> ^f*ifi? S» * o 9 a ». » ?-*flP*T ' ' *-' I'? o»'0«> «°e.cSV< »J>^ ",5s 1 '■'•;.■ „ * •> „ <&■ : 'S»V B Fig. 85. — Sections through the Epidermal Thickenings which Re- present the Mammary Gland in Embryos (A) of 6 cm. and (/■>') of 10.2 CM. sixth months the lobes elongate into solid cylindrical col- umns of cells (Fig. 86) resembling not a little the cylinders which become converted into sudoriparous glands, and each column becomes slightly enlarged at its lower end, from which outgrowths begin to develop to form the acini. 17- THE DEVELOPMENT OF THE HUMAN BODY. A lumen first appears in the lower ends of the columns and is formed by the separation and breaking down of the central cells, the peripheral cells persisting as the lining of the acini and ducts. The elevation of the gland 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 region around the nipple sudoriparous and sebaceous glands develop, the latter also occurring within the nipple area and frequently opening into the extremities of the lacteal ducts. In the areola, as the area surrounding the nipple is termed, other glands, Fig. 86.- -Section through the Mammary Gland of an Embryo of 25 cm. 1, Stroma of the gland. — {From Nagel, after Basch.) known as Montgomery's glands, also appear, their develop- ment resembling that of the mammary gland so closely as to render it probable that they are really rudimentary mammary glands. The further development of the glands, consisting of an increase in the length of the ducts and the development from them of additional acini, continues slowly up to the time of puberty in both sexes, but at that period further growth 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. LITERATURE. 1 73 r The occurrence of a milk ridge has not yet been observed in a sufficient number of embryos to determine whether it is a normal development or is associated with the formation of supernumerary 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 who were ex- amined, and occurs in 47 per cent, of individuals . in certain regions of Germany. The extent to which the anomaly is developed varies from the occurrence of well-developed acces- sory glands to that of rudimentary accessory nipples (hyper- thelia), these latter sometimes occurring in the areolar area of a normal gland and being possibly due in such cases to an hypertrophy of one or more of Montgomery's glands. Although the mammary glands are typically functional only in females in the period immediately succeeding preg- nancy, cases are not unknown in which the glands have been well developed and functional in males (gynecomastia). Fur- thermore, a functional activity of the glands normally occurs immediately 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 Phylo- genie," Ergebnisse der Anat. und Entwickelungsgesch., n, 1893. J. T. Bowen: "The Epitrichial Layer of the Human Epidermis," Anat. Anzeiger, iv, 1889. G. Burckhard: "Ueber embryonale Hypermastie und Hyperthelie," Anat. Hefte, viii, 1897. H. Head: "On Disturbances of Sensation with Special Reference to the Pain of Visceral Disease," Brain, xvi, 1892; xvn, 1894; and xix, 1896. E. KAixiUS:"Ein Pall von Milchleiste bei einem menschlichen Embryo," Anat. Hefte, viii, 1897. T. Okamura: "Ueber die Entwicklung des Nagels beim Menschen," Archiv fur Dermatol, und Syphilol., xxv, 1900. H. Schmidt: "Ueber normale Hyperthelie menschlicher Embryonen und liber die erste Anlage der menschlichen Milchdrusen uberhaupt," Morphol.-Arbeiten, xvn, 1897. C. S. Sherrington: "Experiments in Examination of the Peripheral Distribution of the Fibres of the Posterior Roots of some Spinal Nerves," Philosoph. Trans. Royal Soc, clxxxiv, 1893, and cxc, 1898. H. Strahl: "Die erste Entwicklung der Mammarorgane beim Menschen," Verhandl. Anat. Gesellsch., XII, 1898. 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 consisting 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 sup- ports 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 in- termediate substance is somewhat varied in character, being composed sometimes of white, non-branching non- elastic fibers, sometimes of yellow, branching, elastic fibers; of white, branching, but inelastic fibers which form a reticulum, or of a soft gelatinous substance containing considerable quantities of mucin, as in the tis- sue which constitutes the Whartonian jelly of the umbili- cal cord. Again, in cartilage the matrix is compact and homogeneous, or, in other cases, more or less fibrous, passing over into ordinary fibrous tissue, and, finally, in 174 THE CONNECTIVE TISSUES. 175 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 tis- sues 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 directly repre- sent 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 Fig. 87. — Portion of the Center of Ossification of the Parietal Bone of a Human Embryo. 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 the matrix forms; if this be correct, the distinction which the older views make between the intercellular and intra- cellular origin of the matrix becomes of little importance. Bone differs from the other varieties of connective tis- sue in that it is never a primary formation, but is always 176 THE DEVELOPMENT OF THE HUMAN BODY. wmMm developed either in fibrous tissue or cartilage ; and accord- ing as it is associated with the one or the other, it is spoken of as membrane bone or cartilage bone. In the development of membrane bone some of the connective- tissue cells, which in consequence become known as osteoblasts, deposit lime salts in the matrix in the form of bony spicules which in- crease in size and soon unite to form a network (Fig. 87). The trabecu- lar of the network con- tinue to thicken, while, at the same time, the forma- tion of spicules extends further out into the con- nective-tissue membrane, radiating in all directions from the region in which it first developed. Later the connective tissue which lies upon either surface of the reticular plate of bone thus pro- duced condenses to form a stout membrane, the periosteum, between which and the osseous plate osteoblasts 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 com- pact bone, the inner and outer tables, enclosing and united to a middle plate of spongy bone which consti- tutes the diploe. Fig. 88. — Longitudinal Section of Phalanx of a Finger of an Em- bryo of 3| Months. c, Cartilage trabecular; />, periosteal bone ; po, periosteum ; x, ossification center. — (Szymonoivicz.) THE DEVELOPMENT OF BONE. 177 po pi With bones formed from cartilage the process is some- what different. In the center of the cartilage the inter- cellular matrix becomes increased so that the cells appear to be more scattered and a calcareous deposit forms in it. All around this region of calcification the cells arrange themselves in rows (Fig. 88) and the process of calci- fication extends into the trabecular of matrix which separate these rows. While these processes have been taking place the mesen- chyme surrounding the cartilage has become con- verted into a periosteum (po), similar to that of membrane bone, and its osteoblasts deposit a layer of bone (p) upon the sur- face of the cartilage. The cartilage cells now disap- pear from the intervals be- tween the trabecular of calcified matrix, which form a fine network into which masses of mesen- chyme (Fig. 89, pi), con- taining blood-vessels and osteoblasts, here and there pen- etrate from the periosteum, after having broken through the layer of periosteal bone. These masses absorb portions of the fine calcified network and so transform it into a coarse network, the meshes of which they occupy to form the bone marrow (m), and the osteoblasts which they con- tain arrange themselves on the surface of the persisting trabeculae and deposit layers of bone upon their surfaces. 15 wmm The Ossification Center More Highly Magni- Fig. op Fig. fied. c, Ossifying trabeculae ; cc, cavity of cartilage network; m, marrow cells; p, periosteal bone; pi, ir- ruption of periosteal tissue ; po, periosteum. — (Szymonowicz.) I78 THE DEVELOPMENT OF THE HUMAN BODY. In the mean time the calcification of the cartilage matrix has been extending, and as fast as the network of calcified trabeculse is formed it is invaded by the mesenchyme, until finally the cartilage becomes entirely converted 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 prima- rily distinct bones, a conclusion which may generally be confirmed by a comparison of the bone in question with its homologues in the lower vertebrates. Exceptions to this rule occur in bones situated in the median line of the body, these frequently developing from two centers lying one on either side of the median line, but such cen- ters are usually to be regarded as a double center rather than as two distinct centers, and are merely an expression of the fundamental bilaterality which exists even in. me- dian 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. 90, ep, ep'), the shaft or diaphysis (d) being formed from the primary center. Similar secondary centers appear in marked prominences on bones to which powerful muscles are attached (Fig. 90, a and b), but these, as well as 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 bones to which they be- long. These secondary centers give the necessary firm- ness 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 THE GROWTH OF BONES. 179 always intervenes between the epiphyses and the diaphy- sis. This cartilage continues to be transformed into bone on both its surfaces by the extension of both the epiphy- sial and diaphysial ossification into it and, at the same time, it grows in thickness with equal rapidity until the bone reaches its required length, where- upon the rapidity of the growth of the cartilage diminishes and it gradually becomes completely os- sified, uniting together the epiphy- sis 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 perios- teal bone on the outside of those already present. But in connec- tion with this process an absorp- tion 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 peripheral zone of compact bone surrounding a core of spongy bone, the meshes of the latter being occupied by the mar- row 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 differ- ence depends on the fact that as the periosteal bone Fig. 90.— The Ossifica- tion Centers of the Femur. u. and b, Secondary cen- ters for the great and lesser trochanters; d, diaphysis ; ep, upper and ep', lower epiphy- sis. — (Testut.) l80 THE DEVELOPMENT OF THE HUMAN BODY. increases in thickness, there is a gradual absorption of the spongy bone and also of the earlier layers of periosteal bone, this absorption being carried on by large multi- nucleated cells, termed osteoclasts, derived from the mar- row mesenchyme. By their action the bone is enabled to reach its requisite diameter and strength, without be- coming an almost solid and unwieldy mass of compact bone. During the ossification of the cartilaginous trabecular osteoblasts become enclosed by the bony substance, the Fig. 91.— A, Transverse Section op the Femur op 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 Mad- der Feeding. The heavy black line represents the portion of bone stained by the madder. — {After Flourens.) cavities in which they lie forming the lacunae and processes radiating out from them the canaliculi, so characteristic of bone tissue. In the growth of periosteal bone not only do osteoblasts become enclosed, but blood-vessels also, the Haversian canals being formed in this way, and around these lamellae of bone are deposited by the enclosed osteo- blasts 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 THE VERTEBR.E. 181 food, tinges the bone being formed at the time a distinct red. In pigs fed with madder for a time and then killed a section of the femur shows a superficial band of red bone (Fig. 91, A), 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 thick- ness according to the interval elapsed since the cessation of feeding (Fig. 91, B) ; and if this interval amount to four months, it will be found that the thickness of the uncolored bone be- tween the red bone and the marrow cavity will have greatly diminished (Flourens). The Development of the Skeleton. — Embryo- logically considered, the skeleton is composed of two portions, the axial skeleton, consisting of the skull, the vertebrae, ribs, and sternum, developing from the sclerotomes of the mesodermal somites, and the appendicular skeleton, which includes the pectoral and pelvic girdles and the bones of the limbs, and which arises from the mesenchyme of the somatic mesoderm. It will be convenient to consider first the development of the axial skeleton, and of this the differentiation of the vertebral column and ribs may first be discussed. The Development of the Vertebrae and Ribs.— The mesenchyme formed from the sclerotome of each meso- dermic somite grows inward toward the median line and forms a complete investment for the notochord, and, at Fig. 92. — Transverse Section through the intervertebral Plate of the First Cervical Vertebra of a Calf Embryo of 8.8 MM. be 1 , Intervertebral plate; m 4 , fourth myotome; s, hypochordal bar; XI, spinal accessory nerve. — {Froriep.) I 82 THE DEVELOPMENT OF THE HUMAN BODY. the same time, sends a wing dorsally on each side of the medullary canal, so that this, as well as the notochord, becomes enclosed by a series of mesenchymatous masses, each of which is separated from its predecessor and suc- cessor by a plate of more densely arranged mesenchyma- tous cells (Fig. 92, be 2 ). These intervertebral plates are Fir,. 93. — Longitudinal Section through the OeciriTAL Region and Upper Cervical Vertebr.e of a Calf Embryo of 18.5 mm. bas, Basilar artery ; ch, notochord; JCc 1 - 4 , vertebral centra; Ic 2 -*, inter- vertebral disks; occ, basioccipital; Sc'-*, hypochordal bars. — (Froriep.) portions of the intermuscular septa which occupy the inter- vals between adjacent mesodermie somites and are formed of cells which have wandered from the anterior and poste- rior surfaces of the somites. At first, then, the invest- ment of the notochord and medullary canal is by a series of alternating segmental and intersegmental cellular THE VERTEBR/E. I 83 masses, and the first stage in the development of the verte- brae may be termed the cellular stage. In the second or cartilaginous stage the mesenchyme becomes converted into cartilage in certain definite re- gions. The portions of sclerotomic mesenchyme which surround the notochord become chondrified and form the vertebral centra (Fig. 93, Kc), these structures being therefore segmental and corresponding in position with a pair of spinal nerves, myotomes and dermatomes. The remaining portions of each vertebra and the ribs are devel- oped in the intermuscular septa, and are therefore inter- segmental in position. In the mesial edge of each sep- tum a cartilaginous bar develops, the upper part of which comes into contact with the tip of the corresponding bar of the opposite side to form a neural arch, while the lower end becomes connected with its fellow of the other side by a transverse rod of cartilage which lies below the notochord and is termed the hypochordal bar (Fig. 93, Sc). Furthermore, the ventral edge of each intermuscular sep- tum becomes to a greater or less extent converted into cartilage to form a rib. The neural arches later unite with the centra, their original intersegmental character being thus to a certain extent obscured, but the ribs, which typically alternate with the centra, retain their original position. The hypochordal bars are for the most part merely transitory structures, recalling structures found in the lower vertebrates; in the mammalia they degenerate before the completion of the second stage of development, except in the case of the atlas, whose devel- opment will be described later. The cartilages which form the neural arches are at first simple rods, but later a lateral outgrowth develops on each to form a transverse process and upon the ribs a slighter elevation develops to form the tuberculum. 184 THE DEVELOPMENT OF THE HUMAN BODY. The portions of the sclerotomic mesenchyme which grew up around the medullary canal do not undergo chondrification but become converted into dense fibrous connective tissue, forming the supraspinous and inter- spinous ligaments and the ligamenta subflava. The portions of thejntermuscular septa which immediately surround the notochord and are not concerned in the formation of the hypochordal bars are converted into fibrocartilaginous tissue forming the intervertebral disks (Fig. 93, Ic), while the anterior and posterior inter- vertebral ligaments arise from portions of the mesen- chyme from which the centra are developed. Primarily the notochord traverses the entire series of centra and intervertebral disks as a continuous rod, but as the process of chondrification proceeds the portions which traverse the centra gradually become encroached upon and eventually are completely obliterated, while in the intervertebral disks it continues to grow and per- sists as the masses of pulpy tissue, one of which occupies the center of each disk. 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 vertebrae present a re- duction of the parts derived from the intermuscular septa, the neural arches 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 ver- tebra is formed from the intermuscular septum, its lateral masses and posterior arch being the neural arches, while its anterior arch is the hypochordal bar, which persists THE VERTEBRAE. I8 5 in this vertebra only. A well-developed centrum is also formed, however (Fig. 93), but it does not unite with the parts derived from the corresponding intermuscular sep- tum, but during its ossification unites with the centrum of the axis, forming the odontoid process of that vertebra. The axis consequently consists of two segmental and one intersegmental portion, while the atlas consists of one intersegmental portion only. The extent to which ribs are developed in connection with the various vertebrae also varies considerably. Throughout the cervical region they are very short, the upper five or six being no longer than the transverse pro- cesses with the tips of which their extremities unite at an early stage. In the upper five or six vertebrae a relatively large interval persists between the rib and the transverse process, forming the vertebral foramen, through which the vertebral vessels pass, but in the seventh vertebra 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 to form a longitudinal cartilaginous bar from which the sternum develops (see p. 189). The lower three or four thoracic ribs are successively 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 distin- guished, forming what are known as the accessory tuber- cles. Finally, in the sacral region the ribs are reduced to short flat plates, which unite together to form the lateral masses of the sacrum. They are usually developed only in connection with the first three sacral vertebrae, the last two sacrals and the coccygeals having no ribs. 16 1 86 THE DEVELOPMENT OF THE HUMAN BODY. The limitation of the ribs to the three anterior sacral verte- brae is explained by the fact that primarily the pelvic girdle is in relation only to the last two, whose ribs are consequently sup- pressed. The rib-bearing sacral vertebrae are really members of the lumbar series and only secondarily come into relation with the iliac bones. 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 neural arch at the base of the transverse Fig. 94. — A, A Vertebra at Birth; B, Lumbar Vertebra showing Secondary Centers of Ossification. a, Center for the articular process; c, centrum; el, lower epiphysial plate; en, upper epiphysial plate; na, neural arch; s, center for spinous process ; t, center for transverse process. — (Sappey.) process and gradually extends to form the bony lamina, pedicle, and the greater portion of the transverse and spinous processes; a double center (see p. 178) gives rise to the body of the vertebra ; and each rib ossifies from a single center. These various centers appear early in em- bryonic life, but the complete transformation of the car- tilages into bone does not occur until some time after birth, each vertebra at that period consisting of three parts, a centrum and two halves of an arch, separated by unossified cartilage (Fig. 94, A) . At about puberty secon- THE VERTEBRA. 1 87 dary centers make their appearance; one appears in the cartilage which still covers the anterior and posterior sur- faces of the vertebral centra, producing disks of bone in these situations, another appears at the tip of each spinous and transverse process (Fig. 94, 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 Fig. 95. — A, Upper Surface of the First Sacral Vertebra, and B, Ventral View of the Sacrum showing Primary Centers of Ossification. c. Centrum ; na, neural arch ; r, rib center. — (Sappey.) 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 capit- ulum and tuberosity. In some of the vertebrae modifications of this typical mode of ossification occur. Thus, in the upper five cervi- cal vertebrae the centers for the rudimentary ribs are sup- pressed, ossification extending into them from the neural 1 88 THE DEVELOPMENT OF THE HUMAN BODY. arch centers, and a similar suppression of the costal cen- ters occurs in the lower lumbar vertebra, the first only developing a separate rib center. Furthermore, in the atlas a double center appears in the persisting hypo- chordal bar, and the centrum which corresponds to the atlas, after developing the terminal epiphysial disks, fuses with the centrum of the axis to form its odontoid process, this vertebra consequently possessing, in addition to the typical centers, one (double) other primary and two sec- ondary centers. In the sacral region the typical centers appear in all five vertebrae, with the exception of rib centers for the last one or two (Fig. 95) and two ad- ditional secondary centers give rise to plate-like epi- physes 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 centrum or 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. Occa- sionally the two parts of the double 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 anomalies result from the excessive development of parts. Thus, the rib of the seventh cervical vertebra may sometimes remain distinct and be 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 rib is occasionally found to be imperfect. The Development of the Sternum. — The longitudinal bars which are formed by the fusion of the ventral ends of the anterior eight or nine cartilaginous ribs represent the THE STERNUM. I89 future sternum. At an early period the two bars come into contact anteriorly and fuse together (Fig. 96), 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 cartilaginous clavicles artic- ulate. These are the episternal cartilages (em), which later normally unite with the longitudinal bars and form Fig. 96. — Formation op the Sternum in an Embryo op about 3 cm. cl, Clavicle; em, episternal cartilages. — (Ruge.) part of the manubrium sterni, though occasionally they persist and ossify to form the ossa suprastemalia. The fusion of the longitudinal bars gradually extends back- ward 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 took part in the formation of each bar having separated. The portions of 190 THE DEVELOPMENT OF THE HUMAN BODY. the bars formed by these posterior ribs constitute the ensi- form process. The ossification of the sternum (Fig. 97) partakes to a certain extent of the original bilateral segmental origin of the cartilage, but a marked condensation of the centers of ossification also occurs. In the portion of the cartilage which lies below the junction of the third costal cartilages a series of pairs of centers appears just about birth, each center probably representing an epiphysial center of a correspond- ing rib. Later the centers of each pair fuse and the single centers so formed, extending through the cartilage, eventually unite to form the greater part of the gladiolus. In each of the two uppermost seg- ments, however, but a single center appears, that of the lower segment uniting with the more posterior centers and forming the upper part of the gladiolus, while the uppermost center gives rise to the manubrium, which frequently persists as a distinct bone united to the gladiolus by a hinge- joint. Fig. 97. — Sternum of New-born Child, showing Centers of Ossification. / to VII, Costal cartilages. — (Gegenbaur.) A failure of the cartilaginous bars to fuse produces the condition known as cleft sternum, or if the failure to fuse affects only a por- tion of the bars there results a perforated sternum. A per- foration or notching of the ensiform 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 large bone, the episternum, situated in front of the manubrium in the lowest mammalia and reptilia. It furnishes the articular sur- faces for the clavicles and is possibly formed by a fusion of the THE SKUI.L. I 9 I 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. — Little is as yet known, especially in the human embryo, concerning the origin of the mesenchyme from which the mammalian skull is de- veloped, yet, since there is probably a continuation for- ward into the cranial region of the series of mesodermic somites, it is suppos- able that these furnish the mesenchyme for the skull, just as the more posterior somites furnish that for the vertebra?. In the earliest stages the human skull is rep- resented by a continu- ous mass of mesen- chyme which invests the anterior portion of the notochord and ex- tends forward beyond its extremity into the nasal region, forming a core for the fronto-nasal process (see p. 104). 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 sys- tem. No indications of a segmental origin are to be found in this mesenchyme; as stated, it is a continuous mass, and this is likewise true of the cartilage which later develops in it. The chondrification occurs first along the median line Fig. 98. — Reconstruction op the Chon- drocranium of an embryo of 14 mm. as, AHsphenoid; 60, basioccipital ; bs, basisphenoid ; eo, exoccipital; m, Meckel's cartilage; as, orbitosphenoid ; p, periotic ; ps, presphenoid ; so, sella turcica; s, supraoccipital. — (Levi.) 192 THE DEVELOPMENT OF THE HUMAN BODY. in what will be the occipital and sphenoidal regions of the skull (Pig. 98) 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 (s). No cartilage develops, 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 chondri- fication is proceeding in the regions mentioned, the mesen- chyme which encloses the internal ear becomes converted into cartilage, forming a mass, the periotic capsule (Fig. 98, p), wedged in on either side between the occipital and sphenoidal regions, with which it eventually unites to form a continuous chondrocranium, perforated by fora- mina for the passage of nerves and vessels. The posterior part of the basilar portion of the occipital cartilage presents certain peculiarities of development. In calf embryos there are in this region, in very early stages, four separate condensations of mesoderm corre- sponding to as many mesodermic somites and to the three roots of the hypoglossal nerve together with the first cervical or suboccipital nerve (Froriep) (Fig. 99). These mesenchymal masses in their general characters and rela- tions resemble vertebral centra, and there are good reasons for believing that they represent four vertebrae which, in later stages, are taken up into the skull region and fuse with the primitive chondrocranium. In the human em- bryo they are less distinct than in lower mammals, but since a three-rooted hypoglossal and a suboccipital nerve also occur in man it is probable that the corresponding vertebrae are also represented. Indeed, confirmation of their existence may be found in the fact that during the cartilaginous stage of the skull the anterior condyloid THE SKULL. '93 foramina are divided into three portions by two cartilag- inous partitions which separate the three roots of the hypoglossal nerve. It seems certain from the evidence derived from embryology and compar- ative anatomy that the human skull is composed of a primitive unseg- mental 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 por- tions of the sides of the cranium, its entire roof, as well as the face region, showing no indication of cartilage, the mesen- chyme in these regions being converted into fi- brous connective tissue, which, especially in the cranial region, assumes the form of a dense mem- brane. But in addition to the chondrocranium and the vertebrse incorporated Fig. 99. — Frontal Section through the Occipital and Upper Cervi- cal Regions of a Calf Embryo of 8.7 MM. ai and ai 1 , Intervertebral arteries ; be 1 first cervical intervertebral plate bo, suboccipital intervertebral plate c'- z , cervical nerves; ch, notocbord K, vertebral centrum; m 1 - 3 , occipi- tal myotomes; ro 4 - 5 , cervical myo- tomes; o 1 - 3 , roots of hypoglossal nerve; vj, jugular vein; x and xi, vagus and spinal accessory nerves. — (Froriep.) 194 THE DEVELOPMENT OF THE HUMAN BODY. with it, other cartilaginous elements enter into the com- position of the skull. The mesenchyme which occupies the axis of each branchial arch undergoes more or less complete chondrification, cartilaginous bars being so formed, certain of which enter into very close rela- tions with the skull. It has been seen (p. 97) that each half of the first arch gives rise to a maxillary process which grows forward and ventrally to form the anterior boundary of the mouth, while the remaining portion of the arch forms the mandibular process. Cartilage appears in the posterior or dorsal part of each maxillary process, and the rod so formed applies itself by its ventral end to the under surface of the sphenoid region of the chondrocranium, forming the cartilagi- nous internal ptery- goid plate. The whole of the axis of the mandibular process, on the other hand, 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 cartilage 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 con- venient to consider their further history together with that of the other branchial arch cartilages. The ar- rangement of these cartilages is shown diagrammatic- ally in Fig. 100. Fig. 100. — Diagram showing the Five Branchial Cartilages, / to V. I 1 , Internal pterygoid process of the sphe- noid; At, atlas; Ax, axis; 3, third cervi- cal vertebra. THE SKULL. 1 95 By the ossification of these various parts three catego- ries of bones are formed: (i) cartilage bones formed in the chondrocranium, (2) membrane bones, and (3) car- tilage bones developing from the cartilages of the bran- chial arches. The bones belonging to each of these cat- egories 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 chondrocranium also and in one of the branchial arches the original carti- lage bone becomes ensheathed by membrane bone and eventually disappears completely, so that the adult bone, although represented by a cartilage, is really a membrane bone. And, indeed, this process has proceeded so far in certain portions of the branchial arch skeleton that the original cartilaginous representatives are no longer de- veloped, but the bones are deposited directly in connective tissue. These various modifications 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, indicating, where necessary, the confusion of bones of the various categories. The Ossification of the Chondrocranium. — The ossifica- tion 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. 10 1, bo), the por- tions on either side of this give rise to the two exoccipitals 196 THE DEVELOPMENT OF THE HUMAN BODY. (eo), which bear the condyles, and the -portion above the foramen produces a supraoccipital (so), which represents 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 owes its origin to the fusion of two or some- times four centers of ossification, appearing in the mem- branous roof of the embryonic skull. The bone so formed (ip) represents. the interparietal of lower vertebrates and, at an early stage, unites with the supraoccipital, 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 su- praoccipital takes place in the course of the first or second year after birth, but the basioccipi- tal 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 ver- tebrae, these structures having become completely incor- porated in the chondrocranium, and even the cartilagi- nous partitions which divide the anterior condyloid for- amen usually disappear during the process of ossification. In the sphenoidal region the number of distinct bones which develop is much greater than in the occipital region. Fig. 101. — Occipitai, Bone of a Fetus at Term. bo, Basioccipital; eo, exoccipital ; ip, interparietal; so, supraoccipital. THE SKULL. 1 97 In the first place, the basal portion of the cartilage ossifies to form two bones, an anterior or presphenoid and a poste- rior or basisphenoid (Fig. 102, b), and on each side of each of these an ossification appears giving rise to two lesser wings or orbito sphenoids (os) and two greater wings or alisphenoids (as), and an additional center appears on each side of the basisphenoid to form the lingula (I) . In the course of the third month the lingular fuse with the basisphenoid, the orbitosphenoids unite with the pre- sphenoid at about the sixth month, and a little later the presphenoid and basisphenoid unite, the fusion of the alisphenoids with the basisphenoids not taking place until after birth. The centers which give rise to the alisphe- Fig. 102. — Sphenoid Bone from Embryo op 3J to 4 Months. The parts which are still cartilaginous are represented in black, as, Alisphenoid ; b, basisphenoid; /, lingula; os, orbitosphenoid ; p, internal pterygoid plate. — (Sappey.) noids extend into the external pterygoid plates, but the internal plates (p) are formed by membrane bone which encloses and eventually replaces the pterygoid cartilage derived from the first branchial arch. It seems probable that the upper anterior angle of the alisphenoids arises from a special ossification developing in membrane in this region. The cartilage of the ethmoidal region of the chondro- cranium forms somewhat later than the other portions and consists at first of a stout median mass projecting downward and forward into the fronto-nasal process (Tig. 198 THE DEVELOPMENT OF THE HUMAN BODY. 10 3. lp) afl d two lateral masses (Im), situated one on either side in the mesenchyme on the outer side of each olfactory pit. Ossification of the lateral masses or ectethmoids be- gins relatively early, but it appears in the upper part of the median cartilage only after birth, producing the crista galli and the perpendicular plate, which together form what is termed the mesethmoid. When first formed, these three bones are quite separate from one another, the olfactory and nasal nerves passing down between them to the olfactory pit, but later bony trabecular begin to ex- tend across from the junction between the crista galli and perpendicular plate to the upper part of the ectethmoids and eventually form a fenes- trated horizontal lamella, the cribriform plate. The lower part of the me- dian cartilage does not ossify, but a center appears on each side of the median line in the mesenchyme behind and be- low its posterior or lower bor- der. From these 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 a certain amount of 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 chondrocranium, but is a membrane bone ; its intimate relations with the median ethmoidal carti- Fig. 103. — Anterior Portion op the Base op the Skull of a 6 to 7 Months' Em- bryo. The shaded parts represent car- tilage, cp, Cribriform plate; Im, lateral mass of the eth- moid ; lp, perpendicular plate ; of, optic foramen; os, orbito- sphenoid. — {After von Spee.) THE SKULL. 199 lage, 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 appearance 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 mem- brane lining the nasal cavity. This same process also brings about the formation of the curved plates of bone which project from the inner surfaces of the lateral masses and are known as the superior and middle turbin- ated bones. The inferior and sphenoidal turbinated bones 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 maxillary to form the antrum of Highmore is also produced by outgrowths of the nasal mucous membrane, all these cavities, as well as the eth- moidal 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 forma- tion of five turbinated plates, while in man but three are usually recognized. Not infrequently, however, the human middle turbinated bone shows indications, more or less marked, of a division into an upper and a lower portion, which corre- spond to the third and fourth bones of the typical mammalian arrangement. Furthermore, at the upper portion of the nasal wall, in front of the superior turbinate, a slight elevation, termed the agger nasi, is always observable, its lower edge being prolonged downward to form what is termed the uncinate process of the ethmoid. This process and the agger together represent the first turbinate of the typical arrangement, to which, therefore, the human arrangement may be reduced. 200 THE DEVELOPMENT OF THE HUMAN BODY. A number of centers 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. 104, p). The mastoid process does not really form until several years after birth, being produced by the hollowing and bulging out of a portion of the petrous bone by outgrowths from the lin- ing 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 eth- moidal and sphenoidal cells to the nasal cavities. The re- maining portions of the tem- poral bone are partly formed by membrane bone and partly from the branchial arch skeleton. An ossification appears in the membrane which forms the side of the skull in the temporal region and gives rise to a squamosal 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 Fig. 104. — The Temporal Bone at Birth. The Styloid Process and Auditory Os- sicles are not Repre- sented. p, Petrous bone; s, squamosal; t, tympanic. — (Poirier.) THE SKULL. 20I part of the second branchial arch, whose history will be considered later. The various ossifications which form in the chondro- cranium and the portions of the adult skull which repre- sent them are shown in the following table : Region of Chondrocranium. Ossifications. Occipital, Sphenoidal, Ethmoidal, {Basioccipital Exoccipitals Supraoccipital Basisphenoid 1 Presphenoid J- Lingular j Alisphenoids . Orbitosphenoids Mesethmoid Ectethmoids Inferior turbinated . Sphenoidal turbinated Periotic capsule, Parts of Adult Skull. Basilar process. Condyles. Squamous portion above su- perior nuchal line. Body. Greater wings and external pterygoid plates. Lesser wings, f Lamina perpendicularis. -j Crista galli. (Nasal septum. ("Lateral masses, -j Superior turbinated. (Middle turbinated. / Petrous. \ Mastoid. The Membrane Bones of the Skull. — In the membrane forming the sides and roof of the skull in the second stage of its development ossifications appear, which give rise, in addition to the interparietal 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, while the frontal is formed 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 indi- cations of a median suture, the metopic, are not infre- quently present. Furthermore, ossifications appear in the mesenchyme of the facial region to form the nasal, lachrymal, and 17 202 THE DEVELOPMENT OF THE HUMAN BODY. malar bones, the first two arising from single centers of ossification, while each malar possesses three centers which early unite, though occasionally one or more of their lines of union may persist, producing a divided malar. The vomer, which has already been described, belongs also strictly to the category of membrane bones, as do also the maxillae and 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. Squamosals, Squamous portions of tem- porals. Tympanies, Tympanic plates of temporals. Parietals. Frontal. Nasals. Lachrymals. Malars. Vomer. The Ossification of the Branchial Arch Skeleton. — It has been seen (p. 194) that a cartilaginous bar develops only in the dorsal portion of the maxillary process of the first branchial arch. This cartilage becomes invested by membrane bone which gradually replaces the cartilage and eventually fuses with the sphenoid bone to form its in- ternal pterygoid plate. In the more ventral portions of the maxillary process, however, no cartilaginous skeleton forms, but two membrane bones, the palatine and max- illa, are developed in it, their cartilaginous representatives, which are to be found in lower vertebrates, having been suppressed by a condensation of the development. The THE BRANCHIAL ARCH SKELETON. 203 palatine bone develops from a single center of ossification, but for each maxilla no less than five centers have been described (Fig. 105). 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 contains the canine tooth; a third the portion which contains the incisor teeth ; while the fourth and fifth centers lie above the first and give rise to the inner and outer portions of the orbital plate and the body of the bone. The first, second, fourth, and fifth portions early unite together, but the third center, which really lies in the ventral part of the fronto-nasal process, re- mains separate for some time, forming what is termed the premaxilla, a bone which remains permanently dis- „ ine _, „ „ ^ n c J Fig. 105. — Diagram op the Os- tinct in the majority of the sipications op which the Max- , i_ illa is Composed, as seen prom lower mammals. THE 0uTER SuRPACB . T hb Arrow Passes through the Since the condition known Infraorbital Canal.— (From , r, , . ii r "°» bpee, alter iiappey.) as cleft palate results from a r ' rr ' ' failure of the maxillary pro- cess to unite with the fronto-nasal process (see p. 105), and since the premaxilla develops in the latter and the maxiila in the former, the cleft passes between these two bones and pre- vents their union. The upper end of Meckel's cartilage passes between the tympanic bone and the outer surface of the periotic cap- sule 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 mid- dle ear, the malleus and incus, a description of whose further development may be postponed until a later chap- 204 THE DEVELOPMENT OF THE HUMAN BODY. ter. The lower half of the ventral portion of the cartilage becomes completely invested by a number of flat mem- brane bones, which fuse together so as to enclose the car- tilage together with the vessels and nerve (inferior dental) which lie beside it. Later the cartilage disappears and a canal containing the vessels and nerve is left traversing the fused bones which represent the horizontal ramus and the lower part of the vertical ramus of the mandible. The upper part of the vertical ramus is formed of membrane bone also, but in this case the bone lies entirely on the outer side of the cartilage, whence the position of the dental fora- men on the inner surface of the ramus. The upper half of the ventral portion of the cartilage which corresponds to this upper part of the ramus undergoes a degeneration, forming the spheno-tnandibular ligament, and, in the later stages of development, cartilage develops, quite inde- pendently of the original Meckelian cartilage, at the sym- physis, the articular surface, the coronoid process and the angle, and may undergo ossification, becoming eventually united to the membrane bone ; these cartilages are to be regarded as secondary epiphysial cartilages. The upper part of the cartilage of the second branchial arch also lies within the tympanic cavity and ossifies to form the stapes, while the portion of the cartilage imme- diately ventral to this ossifies as 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 ob- served in the length of the styloid processes and of the lesser cornua 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 THE BRANCHIAL ARCH SKELETON. 205 cornua of the hyoid are formed by the ossification of the cartilages of the third arch, and the body of the bone is Fig. 106. — Diagram showing the Categories to which the Bones of the Skull Belong. The unshaded bones are membrane bones, the shaded represent the chondrocranium, while the black represent the visceral arch elements. AS, Alisphenoid; ExO, exoccipital; F, frontal; Hy, hyoid; IP, interparietal; M, malar; Mn, mandible; Mx, maxilla; NA, nasal; P, parietal; Pe, periotic; SO, supraoccipital; Sq, squamosal; St, styloid process ; Th, thyreoid cartilage ; Ty, tympanic. formed from a cartilaginous plate, the copula, which unites the ventral ends of the two arches concerned. 206 THE DEVELOPMENT OF THE HUMAN BODY. Finally the cartilages of the fourth and fifth arches 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. 106) shows the vari- ous structures derived from the branchial arch skeleton as well as some of the other elements of the skull, and a re- sume* of the fate of the branchial arches may be stated in tabular form as follows, the parts represented by car- tilage which becomes replaced by membrane bone being printed in italics, while membrane bones which have no cartilaginous representatives are enclosed in brackets : (Maxilla). (Palatine). Pterygoid = internal pterygoid process of sphenoid. 1st arch, < Malleus. I Incus. Spheno-mandibular ligament. Mandible. I Stapes. Styloid process of the temporal. Stylo-hyoid ligament. Lesser cornu of hyoid. 3d arch, Greater cornu of hyoid. 4th and 5th arches, . . Thyreoid cartilage of larynx. The Development of the Appendicular Skeleton. — While 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 metameres. This mesenchyme forms the core of the limb bud and becomes converted into cartilage, by the ossifica- tion of which all the bones of the limbs, with the possible exception of the clavicle, are formed. Of the bones of the pectoral girdle the clavicle re- quires further study before it can be certain whether it is to be regarded as a pure cartilage bone or a combination of THE PECTORAL GIRDLE. 207 cartilage and membrane ossifications (Gegenbaur). It is the first bone of the skeleton to ossify, its center appearing at about the sixth week of development. The tissue in which the ossification forms has certain peculiar characters, and it is difficult to say whether it is to be regarded as cartilage which, on account of the early differentiation of the center, has not yet become thoroughly differentiated histologically, or as some other form of connective tissue. However that may be, true cartilage de- velops on either side of the ossifying region, and into this the ossification gradually extends, so that at least a portion of the bone is preformed in cartilage. 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 (Pig. 107, co), the rudimentary representative of the cora- coid bone which extends between the scapula and ster- num 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. Fig. 107 — The Ossification Cen- ters op the Scapula. 6, and c, Secondary centers for the angle, vertebral border, and acromion ; co, center for the coracoid process. — (Testut.) 208 THE DEVELOPMENT OF THE HUMAN BODY. The humerus and the bones of the forearm are typical 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 tuber- osity, and usually a third for the lesser tuberosity, while at the distal end there is a center for each condyle, 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 possess a single epiphysial center for each ex- tremity in addition to the primary center for the shaft, and the ulna possesses also an epiphysial center for the olecranon process. The embryological development of the carpus is some- what complicated. A cartilage is found representing each of the bones normally occurring in the adult (Fig. 1 08), 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, radiate, intermedium, and ulnare; and a distal one composed of four elements, termed carpa- lia. In addition, a cartilage, termed the pistform, is found on the ulnar side of the proximal row and is gener- ally 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 centrale (Fig. 108, c) and occupies a position between the cartilages of the proximal and distal rows and appar- THE SKELETON OF THE ARM AND HAND. 209 ently corresponds to a cartilage typically present in lower forms and ossifying to form a distinct bone. In the hu- man carpus its fate varies, as it may either disappear or unite with other cartilages, that with which it most usu- ally fuses being probably the radiale. There is evidence also to show that another of the accessory cartilages unites with the ulnar element of the distal row, representing the carpale V typically present in lower forms. Each of the ele- ments corresponding to an adult bone ossi- fies from a single center with the exception of carpale IV-V, which has two centers, a further indication of its composite charac- ter. The relation of the cartilages to the adult bones may be seen from the table given on page 212. 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 appears 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 metacarpals are at the distal ends of the bones, except in the case of the metacarpal of the thumb, which re- sembles the phalanges in having its epiphysis at the distal end. 18 Fig. 108. — Reconstruction of an Em- bryonic Carpus. c, Centrale; cu, cuneiform; lu, semilunar; m, os magnum ; p, pisiform ; sc, sca- phoid; t, trapezium; tr, trapezoid; u, unciform. 2IO THE DEVELOPMENT OF THE HUMAN BODY. Each innominate bone appears as a somewhat oval plate of cartilage whose long axis is directed almost at right angles to the vertebral column and which is in close rela- tion with the fourth and fifth sacral vertebra?. As devel- opment proceeds a rotation of the cartilage, accompanied 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. Ossifica- tion appears at three points in each cartilage, one in the upper part to form the ilium (Fig. 109, il) and two in the lower part, the anterior of these giving rise to the pubis (p), while the posterior produces the ischium (is). At birth these three bones are still sep- arated from one an- other by a Y-shaped piece of cartilage whose three limbs meet at the bottom of the acetabu- lum, but later a secondary center appears in this carti- lage and unites the three bones together. The central part of the lower half of each original cartilage plate does not undergo complete chondrification, but remains mem- branous, constituting the obturator membrane which closes the obturator foramen. In addition to the Y-shaped secondary center, other Fig. 109. — The Ossification Centers of the os innominatum. a, b, c, and d, Secondary centers for the crest, anterior inferior spine of symphysis, and ischial tuberosity; il, ilium; is, ischium; p, pubis. — (Testut.) THE PELVIC GIRDLE AND LOWER LIMB SKELETON. 211 epiphysial centers appear in the prominent portions of the cartilage, such as the pubic crest (Fig. 109, 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, and fibula each develop from a single primary center for the shaft and an upper and a lower epiphysial center, the femur possessing, in addition, epi- physial centers for the greater and lesser trochanters (Fig. 90). The patella does not belong to the same cate- gory 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 the fibulare, and of a distal row of four tarsalia. Be- tween these two rows a single cartilage, the centrale, is interposed. Each of these cartilages ossifies from a sin- gle 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 represents 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 inser- tion 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: 212 THE DEVELOPMENT OF THE HUMAN BODY. Carpus. Tarsus. Cartilages. Bones. Bones. Cartilages. Radiale Intermedium Ulnare Sesamoid carti- lage Centrale Carpale I Carpale II Carpale III Carpale IV \ Carpale V J Scaphoid Semilunar Cuneiform Pisiform Fuses with sca- phoid Trapezium Trapezoid Os Magnum Unciform Astragalus < Os Calcis Navicular Int. Cuneiform Mid. Cuneiform Ext. Cuneiform Cuboid | Tibiale Intermedium Fibulare Centrale Tarsale I Tarsale II Tarsale III Tarsale IV Tarsale V The development of the metatarsals and phalanges is exactly similar to that of the corresponding bones of the hand (see p. 209). 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 converted 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 mesen- chyme. In the former case the various ossifications as they extend will come into contact with their neighbors and will either fuse with them or will articulate with them directly, forming a suture. When, however, a portion of unmodified mesenchmye intervenes between two cartilages, the mode of articula- tion of the bones formed from these cartilages will vary. The intermediate mesenchyme may in time undergo chon- drification and unite the bones in an almost immovable articulation known as a synchondrosis (e. g., the sacro- iliac articulation) ; or a cavity may appear in the center of the intervening cartilage so that a slight amount of move- THE JOINTS. 213 merit of the two bones is possible, forming an amphiarthro- sis (e. g., the symphysis pubis) ; or, finally, the intermediate mesenchyme may not chondrify, but its peripheral por- tions may become converted into a dense sheath of con- nective tissue (Fig. 1 10, c) which surrounds the adjacent ends of the two bones like a sleeve, forming the capsular ligament, while the central portions degenerate to form a cavity. The bones which enter into such an articulation are more or less freely movable upon one another and the Fig. 110. — Longitudinal Section through the Joint of the Great Toe in an Embryo of 4.5 cm. c, Capsular ligament; i, intermediate mesenchyme which has almost disappeared in the center; p 1 and p 1 , cartilages of the .first and second phalanges. — (Nicolas.) 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 rein- forcing ligaments, while other strong fibrous bands, which may pass from one bone to the other forming accessory ligaments, are shown by comparative studies to be in 214 THE DEVELOPMENT OF THE HUMAN BODY. many cases degenerated portions of what were originally muscles. In certain diarthroses, such as the temporo-mandibular and claviculo-sternal, the whole of the central portions of the intermediate 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 joints have a similar significance. LITERATURE. A. Bernays: "Die Entwicklungsgeschichte des Kniegelenks des Menschen mit Bemerkungen fiber die Gelenke im Allgemeinen," Morpholog. Jahrbuch, iv, 1878. E. Dursy: "Zur Entwicklungsgeschichte des Kopfes des Menschen und der hoheren Wirbelthiere," Tubingen, 1869. V. von EbnEr: "Ueber die Beziehungen der Wirbel zu den Urwirbeln," Sitzungsberichte der kais. Akad. Wien, ci, 3te Abth., 1892. A. Froriep: "Zur Entwicklungsgeschichte der Wirbelsaule, insbesondere des Atlas und Epistropheus und der Occipitalregion," Archiv fitr Anat. und Physiol., Anat. Abth., 1886. C. Gegenbaur: "Ein Fall von erblichem Mangel der Pars acromialis Clavicular, mit Bemerkungen fiber die Entwicklung der Clavicula," Jenaische Zeitschr. fiir medic. Wissensch., I, 1864. HenkE and ReyhER: "Studien fiber die Entwickelung der Extremitaten des Menschen, insbesondere der Gelenkflachen," Sitzungsberichte der kais. Akad. Wien, lxx, 1875. M. Jakoby : " Beitrag zur Kenntnis des menschlichen Primordialcraniums," Archiv fiir mikrosk. Anat., xuv, 1894. H. LEBOUCQ: "Recherches sur la morphologie du carpe chez les mam- miferes," Archives de Biolog., v, 1884. G. Levi: "Beitrag zum Studium der Entwickelung des knorpeligen Pri- mordialcraniums des Menschen," Archiv fur mikrosk. Anat., lv, 1900. F. P. Mall: "The Development of the Connective Tissues from the Con- nective-tissue Syncytium," Amer. Jour. Anat., i, 1902. W. van NoordEn: "Beitrag zur Anatomie der knorpeligen Schadelbasis LITERATURE. 2 I 5 menschlicher Embryonen," Archiv }ur Anat. und Physiol., Anal Abth., 1887. Rambaut ET Renault: "Origine et developpement des Os," Paris, 1864. E. Rosenberg : ' ' Ueber die Entwickelung der Wirbelsaule und das Centrale carpi des Menschen," Morpholog. Jahrbuch, I, 1876. G. RugE: " Untersuchungen iiber die Entwickelungsvorgange am Brust- bein des Menschen," Morpholog. Jahrbuch, vi, 1880. G. Thilenius: "Untersuchungen iiber die morphologische Bedeutung accessorischer Elemente am menschlichen Carpus (und Tarsus)," Morpholog. Arbeiten, v, 1896. P. A. Zachariad^s: "Recherches sur le developpement du tissu con- junctiv," Comptts Rendus de la Soc de Biolog. Paris, Ser 10, v, 1898. 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 allied 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.— Non-striated muscular tissue is formed by the direct con- version of mesenchyme cells into muscle-fibers, the exact details of the conversion being as yet unknown. The fibers are sometimes more or less scattered in the general connective tissue or may be grouped into small bundles or into layers. They are formed from the mesenchyme of the dermatomes and from that of the somatic and splanchnic layers of the mesoderm, but never from the myotomes of the mesodermic somites. The cells from which the heart musculature develops show at first an irregular protoplasmic reticulum (Fig. in, A) which later becomes regularly arranged so as to 216 THE DEVELOPMENT OF MUSCLE TISSUE. 217 give the cell when viewed in longitudinal section the ap- pearance of being composed of a series of disks arranged in closely approximated rows, each disk being one of the meshes bounded by the reticulum fibers. Later each mesh or disk (Fig. 111, B) becomes divided into smaller disks by reticulum trabeculse which meet in the centers of the original disks, and at the lines along which these sec- ondary trabecular meet the reticulum thickens to form a fibril (Fig. 1 1 1, C, /). The formation of the fibrils begins at the periphery of the cell and proceeds centrally, though even in the adult condition there is an area surrounding Fig. ill. — Cross-sections of Heart-muscle Cells from Pig Em- bryos OF (A) 10 MM. AND (B AND C) 20 MM. /, Fibril; /, large disk; n, nucleus; s, small disk. — (Macallum.) the nucleus in which they do not develop. The cells so altered arrange themselves at first in bundles distinctly separated from one another, so that the heart-wall has a somewhat spongy appearance, but later the various bundles fuse more or less completely to form a solid mass, the original condition being retained only in the auricular appendices and on the inner surfaces of the ventricles, where the bundles form the columnar carneae and musculi papillares. The Histogenesis of Striated Muscular Tissue. — The his- togenesis of the striated muscle-fibers resembles very 2l8 THE DEVELOPMENT OF THE HUMAN BODY. closely that described as occurring in the heart muscle, with the difference that the fibrils are developed through- out the entire thickness of the cell, the nucleus originally present disappearing, while new nuclei (Fig. 112, B), in considerable number, make their appearance at the per- iphery of the fiber, some of these being possibly formed by a division of the original nucleus. The formation of the fibrils is completed in embryos of about 17 cm. in length, and up to this period the increase in thickness of a muscle Fig. 112. — Cross-section of a Muscle from the Thigh of a Pig Em- bryo 75 mm. Long. A, Original central nucleus; B, new peripheral nucleus. — {Macallum.) is probably due to a certain extent to an increase in the actual number of fibers, new fibers forming by the division of those already existing. Subsequently, however, this rfiode of growth ceases, the further increase of the muscle depending upon an increase in size of its constituent ele- ments (Macallum). The Development of the Skeletal Muscles. — It has already been pointed out that all the skeletal muscles of THE SKELETAL MUSCLES. 21 Q the body, with the exception of those connected with the branchial arches, are derived from the myotomes of the mesodermic somites, even the limb muscles probably hav- ing such an origin, although the cells of the myotomes as they grow out into the limb buds early lose their epithe- lial arrangement and become indistinguishable from the somatic mesenchyme which forms the axial core of the limb. The various fibrils 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 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 myotome belonging to the same segment is established at a very early period of development and per- sists throughout life, no matter what changes of fusion, splitting, or migration the myotome may undergo, it is possible to trace out more or less completely the history of the various myotomes by determining their segmental innervation. It is known, for example, that the latissi- mus dorsi arises from the seventh and eighth* cervical myotomes, but later undergoes a migration, becoming at- tached to the lower thoracic and lumbar vertebrae 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 * This enumeration is based on convenience in associating the myo- tomes with the nerves which supply them. The myotomes mentioned are those which correspond to the sixth and seventh cervical vertebrae. 220 THE DEVELOPMENT OF THE HUMAN BODY. associated, its nerve-supply consequently indicating the extent of its migration. By following the indications thus afforded, it may be seen that the changes which occur in the myotomes may be referred to one or more of the following processes : i . A longitudinal splitting into two or more portions, a process well illustrated by the trapezius and sterno- mastoid, which have differentiated by the longitudinal splitting of a single sheet and contain therefore portions of the same myotomes. The sterno-hyoid 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. Ex- amples 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 triangularis sterni of the thorax. 3. A fusion of portions of successive myotomes to form a single muscle, again a process of frequent occurrence, and well illustrated 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 erector spinas. 4. A migration of parts of one or more myotomes over others. An example of this process is to be found in the latissimus dorsi, whose history has already been re- ferred to, and it is also beautifully shown by the serratus magnus 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 myo- tome. This process has played a very considerable part THE SKELETAL MUSCLES. 221 in the evolution of the muscular system in the vertebrates. When a muscle normally degenerates, it becomes con- verted 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 occi- pito-frontalis is due to this process 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 oblique and transverse muscles of the abdomen are also good ex- amples. Indeed, in comparing one of the mammals with a mem- ber 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 infer- ence being that these connective-tissue structures (fascia?, aponeuroses, ligaments) represent portions of the muscu- lar tissue of the lower form (Bardeleben). Many of the accessory ligaments occurring in connection with diar- throdial joints apparently owe their origin to a degenera- tion of muscle tissue, the external lateral ligament of the knee-joint, for instance, being probably a degenerated portion of the peroneus longus, while the great sacro- sciatic ligament appears to 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 comparatively 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 222 THE DEVELOPMENT OF THE HUMAN BODY. abdominal walls. In the musculature associated with the branchial arches the alteration in the direction of the fibers occurs even in the fishes, in which the original direction of the muscle-fibers is very perfectly retained in other myo- tomes, the branchial muscles, however, being arranged parallel with the branchial cartilages or even passing dorso-ventrally between the upper and lower portions of an arch, and so forming what may be regarded as a con- strictor of the arch. This alteration of direction dates back so far that the constrictor arrangement may well be taken as the primary condition in studying the changes which the branchial musculature has undergone in the mammalia. It would occupy too much space in a work of this kind to consider in detail the history of each skeletal muscle of the human body, but a statement of the general plan of their development will not be out of place. For conve- nience the entire system may be divided into three por- tions — 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. 1 24) 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 accomplished, however, a longitudinal splitting of each myotome occurs, whereby there is sepa- rated off a dorsal portion which gives rise to a segment of the dorsal musculature of the trunk and is supplied 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 THE TRUNK MUSCULATURE. 223 extending the entire length of the trunk and being at- tached 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 myo- Fig. 113. — Embryo of 13 mm. showing the Formation ok the Rectus Muscle. — (Mall.) tomes are derived the muscles belonging to the three deepest layers of the dorsal musculature, the more super- ficial layers being composed of muscles belonging to the limb system. Further longitudinal and tangential divi- sions and a fusion of successive myotomes bring about the conditions which obtain in the adult dorsal musculature. 224 THE DEVELOPMENT OF THE HUMAN BODY. While the myotomes are still some distance from the mid-ventral line another longitudinal division affects their ventral edges (Fig. 113), portions being thus sepa- rated which later fuse more or less perfectly to form longi- tudinal bands of muscle, those 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-hyo-glossus * in the neck region. In the thoracic region this rectus set of muscles, as it may be termed, is not represented except as an anomaly, its ab- sence 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 colli and psoas, which lie beneath the vertebral column and hence have been termed hyposkeletal muscles (Huxley). More ven- trally three sheets of muscles, 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 transversalis muscles, in the thorax the intercostals and the triangularis sterni, while in the neck these portions of some of the myotomes disappear, those of the remainder giving rise to the scaleni muscles, portions of the trapezius and sternomastoid (Bolk), and possibly the hyoglossus and st)doglossus. In the abdominal region, and to a con- siderable extent in the neck also, the various portions of * 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. THE TRUNK MUSCULATURE. 22 5 myotomes fuse together, but in the thorax they retain in the intercostals their original distinctness, being separated by the ribs. The table on page 226 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 por- tions are concerned probably all these myotomes as far back as the fifth sacral are represented in the erector spinae, but the ventral portions from the first lumbar myo- tome onwards 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 portions of the remaining lumbar and of the first and second sacral myotomes being devoted to the formation of the musculature of the lower limb. The ventral portions of the third and fourth sacral myo- tomes are represented, however, by the levator ani and coccygeus, and are the last myotomes which persist as mus- cles in the human body, although traces of still more pos- terior 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 myotomes. At a time when the cloaca (see p. 296) is still present, a sheet of muscles lying close beneath the integument forms a sphincter around its opening (Fig. 114). On the development of the partition which divides the cloaca into rectal and urinogenital portions, the sphincter is also divided, its more posterior portion persisting as the external sphincter ani, while the anterior part gradually 19 226 THE DEVELOPMENT OF THE HUMAN BODY. (0 H J u w en 3 en s »"■• to J < en (n 3 en 5S o >1 O J3 g>-a O o — o 8 0, > £.►, «a O £" ' » — ■ "— " d en w *4J -5* u Cj-H tfj D cd CVd •d s to ■ a i 2 S^-d o'S. ■a'Sl ^ p-G cfl ra eu J.^^"P."g. > OS HI u in B en o o J! HI*! ' — y — ' -. — ■— -~-— ~~ ■C ,3 en W J u en a § 8 " S •d +j <4 to u -t-J .a t •« ffl — •« CtJ 'B 3 "3 "3 X h en a 0) -u o a 05 a. -Is w .St- O O w *D rt ■§ B 3 ° ., i>.= X .« 3 a 1 '-^ tn H en S . m en E « "5 '3 3 S ^2 en Sil-2 3"d f^H °-3 a O to < Z s n < 8 c ■d en efl O en < P4 dn «j t-i «ff m ^r- S _, o 0) 3 H ll o 11 +J >• +J tj cej i4 ^_ X z ^_, o ri "c t-< 5 w +j u tw c * C C > THE CRANIAL MUSCULATURE. 227 differentiates into the various perineal muscles (Popow- sky). 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 indistinctness in man is a secondary condition. Exactly how many of these somites are represented in the mammalian head it is im- A B Fig. 114. — Perineal Region op Embryos of (A) Two Months and (B) Four to Five Months, showing the Development op the Peri- neal Muscles. dc, Nervus dorsalis clitoridis ; p, pudendal nerve ; sa, sphincter ani ; sc, sphincter cloacae; sv, sphincter vaginae. — (Popowsky.) possible to say, but it seems probable, from comparison with lower forms, that there is a considerable number. The majority of them, however, early undergo degenera- tion, and in the adult condition only three are recogniz- able, two of which are praeoral in position and one post- oral. 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 supe- rior oblique muscles innervated by the fourth nerve, while 228 THE DEVELOPMENT OF THE HUMAN BODY. from the postoral myotomes the external 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 all other voluntary muscles of the body in the fact that they are derived from the branchiomeres formed by the segmenta- tion of the cephalic ventral mesoderm. These muscles, therefore, are not to be regarded as equivalent to the myo- tomic muscles if their embryological origin is to be taken as a criterion of equivalency, and in their case 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 branchiomeric muscles to distinguish them 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 branchiomeric muscles are, strictly speak- ing, visceral muscles, and indeed give rise to muscle sheets (the constrictors of the pharynx) which surround the upper or pharyngeal portion of the digestive tract. It is possible, then, that the homology is not so strained as might appear, but further discussion of it may profitably be deferred until the cranial nerves are under consideration. The skeleton of the first branchial arch becomes con- verted partly into the jaw apparatus and partly into audi- tory ossicles, and the muscles derived from the correspond- THE CRANIAL MUSCULATURE. ■ 229 ing branchiomere become the muscles of mastication (the temporal, masseter, and pterygoids), the mylohyoid, ante- rior belly of the digastric, the tensor palati and the ten- sor tympani. The nerve which corresponds to the first branchial arch is the trigeminus or fifth, and conse- quently 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 branchiomere, 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 myoides 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. 115). The degeneration of the upper part of the third arch produces a shifting forward of one of the muscles derived from its branchiomere, the stylopharyngeus arising from the base of the styloid process. The innervation of this muscle by the ninth nerve indicates, 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 corre- sponding branchiomeres constitute the muscles of the Temp. ^ ularispostl Facialis collil ~ubcu£t colli meet,./ B Fig. 115. — Head of Embryos (A) of Two Months and (B) op Three Months showing the Extension of the Seventh Nerve upon the Face. — (Popawsky.) 230 THE LIMB MUSCLES. 23 I larynx, together with the remaining portions of the con- strictors 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 addition, two of the extrinsic muscles of the tongue, the palato- glossus and chondroglossus, belong to the fourth of fifth branchiomere, although the remaining muscles of this physiological set are myotomic in origin. Finally, portions of two other muscles should probably be included in the list of branchiomeric muscles, these muscles being the trapezius and sternomastoid. It has already been seen that these muscles are partly derived from the cervical myotomes, but they also appear to be innervated in part by the spinal accessory, and since the motor fibers of this nerve are serially homologous with those of the vagus it would seem that the muscles which they supply are probably branchiomeric in origin. Obser- vations on the development of these muscles, determining their relations to the branchiomeres, are necessary, how- ever, before their morphological significance can be re- garded as definitely settled. The table on page 232 shows the relations of the various cranial muscles to the myotomes and branchiomeres, as well as to the motor cranial nerves. The Limb Muscles. — In the human embryo the tissue from which the limb muscles develop is indistinguishable in early stages from the core of somatic mesenchyme which gives rise to the limb skeleton. And while it is possible that the muscles may have a common origin with the skeletal tissue, yet it seems more probable that they are really derived from the myotomes, and that the unseg- mented and mesenchymatous character of the tissue from which they differentiate is a secondary condition. For it 232 THE DEVELOPMENT OF THE HUMAN BODY. ■a t Trapezius. Sterno- mastoid. J3 , °*? ■ Is . • ■s;eS r .tirt3'S^8)po u -H irtg O A< t-> < S fc O •§ Stiff O d oj Ah CO O -4-J PI > CO -4-* in S3 w us Mi "3 *-" .a -r . . 5 o-m i to ^x>w^;j-.-i-»t-cx ft ft! >**o A "S « \ti Jh o oj o « ei S u ■* O P cd fi^ «^ ") s Li 3 ■O ft ■2 3 us CX_Q 3 O co a o Si ' u ' Zt 3J I s a s g. I'SaSg Whhh « > <* w Z P 01 en oS 3 o OS(0 <: S J S S o CQ THE LIMB MUSCLES. 233 seems certain that a very considerable amount of con- densation of development occurs in the limb muscles; prolongations from the myotomes have been observed extending out into the limb buds in some of the lower vertebrates; and, furthermore, the distribution of the nerves in the limbs of the adult seem to indicate clearly a segmental arrangement of both the muscles and the cutis. Accepting, then, the idea that the limb muscles are de- rived from myotomes, it may be supposed that the myo- tomes of the segments corresponding to each limb, in their growth ventrally, extend outward over the tip of the core of skeletal mesenchyme and return to the side of the trunk in the manner shown in Fig. 116. Each myotome thus gives rise to a portion of both the dorsal and the ventral musculature of the limb and forms a loop, as it were, ex- tending lengthwise over the axis of the limb. Since the first of the myotome loops which pass out into each limb lies along the anterior edge of the limb bud, the muscu- lature derived from it will, in the adult, be situated along the outer side of the arm and the inner side of the leg, because of the opposite rotation which the two limbs undergo during development (seep. 107). If, now, this loop idea be tested by the distribution of the nerves to the lower limb, it will be found that the first myotome to pass out upon the dorsum of the ilium is the second lumbar, and following that there are met succes- sively, from before backward, the remaining lumbar and the first and second sacral myotomes. The arrangement of these myotomes upon the dorsal surface of the pelvis and the muscles to which they contribute may be seen from Fig. 117. In this portion of their course they repre- sent portions of the dorsal half of the loops, the remaining portions extending downward on the anterior surface of the =34 THE DEVELOPMENT OF THE HUMAN BODY. leg. Only the sacral myotomes, however, extend through- out the entire length of the limb into the foot, the second lumbar myotome extending down only to about the middle of the thigh, the third to about the knee, the fourth to about the middle of the tibial region, and the fifth as far as the base of the fifth metatarsal bone. Each of these dm Fig. 116. — Diagram of a Segment of the Body and Limb. bl, Axial blastema; dm, dorsal musculature of body; rl, nerve to limb; s, septum between dorsal and ventral musculature; str.d, dorsal layer of limb musculature; tr.d and tr.v, dorsal and ventral divisions of a spinal nerve ; vm, ventral musculature of the body. — {Kollmann.) myotomes at the point indicated bends toward the inner side of the leg and passes upward again on its posterior sur- face toward the trunk, representing in this portion of its course the ventral portion of the loop. The two sacral myotomes can be traced into the foot, the first giving rise THE LIMB MUSCLES. 235 to the musculature of the inner portion and the second to // Fir. 117. — External Surface of the Os Innominatum showing the Attachment of Muscles and the Zones Supplied by the Various Nerves. 12, Twelfth thoracic nerve; / to V, lumbar nerves; 1 and 2, sacral nerves. — (Bolk.) that of the outer portion, and, extending to the tips of the toes, they are reflected upon the plantar surface and so 236 THE DEVELOPMENT OF THE HUMAN BODY. loop upward on the posterior surface of the leg toward their point of origin from the trunk. In a transverse section through any part of the limb, Fig. 118. — Sections through (A) the Thigh and (B) the Calf show- ing the Zones Supplied by the Nerves. The Nerves are Num- bered in Continuation with the Thoracic Series. — {A after ' Bolk.) accordingly, each myotome concerned will be cut twice, once in the descending (dorsal) and once in the ascending (ventral) portion of the loop, the arrangement found being THE LIMB MUSCLES. 237 that represented in Fig. 118. The modifications under- gone by the various myotomes throughout the course of their loops resemble those already described as occurring in the trunk myotomes. Thus, each of the muscles repre- sented in Fig. 1 18, B, is formed by the fusion of elements derived from two or more myotomes ; the soleus and gas- trocnemius represent deep and superficial layers formed from the same myotomes by a horizontal (tangential) split- ting, these same muscles contain a portion of the second Fig. 119. — Section through the Upper Part of the Arm showing the Zones Supplied by the Nerves. 5v to 7v, Ventral branches; 5d to 8d, dorsal branches of the cervical nerves. — (Bo/fe.) sacral myotome which overlaps muscles composed only of higher myotomes, and the intermuscular septum between the peroneus brevis and the flexor longus hallucis repre- sents a portion of the third sacral myotome which has degenerated into connective tissue. A similar arrangement occurs in the myotomes entering into the formation of the musculature of the upper limb These are the fourth, fifth, sixth, seventh, and eighth cer- vical and the first thoracic myotomes, and of these only 238 THE DEVELOPMENT OF THE HUMAN BODY. the eighth cervical and first dorsal extend as far as the tips of the fingers. The arrangement of the myotomes in the upper part of the brachium may be seen from Fig. 1 19, in connection with which it must be stated that the fourth cervical myotome does not extend down to the level at which the section is taken and that the ventral portion of the loop of the eighth cervical and both portions of that of the first dorsal are represented only by connective tissue in this region. LITERATURE. C R. Bardeen and W. H. Lewis: "Development of the Limbs, Body- wall, and Back in Man," The American Journal of Anat., I, 1901. K. BardELEben: "Muskel und Fascia," Jenaische Zeitschr. fur Nalur- ■wissensch., xv, 1882. L. Bolk: "Beziehungen zwischen Skelett, Muskulatur und Nerven der Extremitaten, dargelegt am Beckengiirtel, an dessen Muskulatur sowie am Plexus lumbosacralis," Morphol. Jahrbuch, xxi, 1894. L. Bolk : ' * Rekonstruktion der Segmentirung der Gliedmassenmuskulatur dargelegt an den Muskeln des Oberschenkels und des Schultergurtels," Morphol. Jahrbuch, xxn, 1895. L. Bolk: "Die Sklerozonie des Humerus," Morphol Jahrbuch, xxiii, 1896. L. Bolk: " Die Segmentaldifferenzierung des menschlichen Rumpfes und seiner Extremitaten," I, Morphol. Jahrbuch, xxv, 1898. W P. Herringham: '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. Jour, of Anat., I, 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. F. P. Mall: "Development of the Ventral Abdominal Walls in Man," Journ. of Morphol., xiv, 1898. 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 quer- gestreiften Muskel von weissen Ratten," Anat. Anzeiger, xv, 1899. LITERATURE. 239 I. Popowsky : " Zur Entwicklungsgeschichte des N. facialis beim Men- schen, "Morphol. Jahrbuch, xxm, 1896. I. Popowsky: "Zur Entwickelungsgeschichte der Dammmuskulatur beim Menschen," Anat. Hefte, xn, 1899. L. Rethi: "Der peripherea Verlauf der motorischen Rachen- und Gau- mennerven," Sitzungsber. der kais. Akad. Wissensch. Wien. Math.- Naturwiss. Classe, en, 1893. C. S. Sherrington: "Notes on the Arrangement of Some Motor Fibers in the Lumbo-sacral Plexus," Journal of Physiol., xm, 1892. J. B. Sutton: "Ligaments, their Nature and Morphology," London, 1897. CHAPTER IX. THE DEVELOPMENT OF THE CIRCULATORY AND LYMPHATIC SYSTEMS. At present nothing is known as to the earliest stages of development of the circulatory system in the human em- bryo, but it may be supposed that they resemble in their fundamental features what has been observed in such forms as the rabbit and the chick. In both these the sys- tem originates in two separate parts, one of which, located in the embryonic mesoderm, gives rise to the heart, while the other, arising in the extra-embryonic mesoderm, forms the first blood-vessels. It will be convenient to consider these two parts separately, and the formation of the blood-vessels may be first described. In the rabbit the extension of the mesoderm from the embryonic region where it first appears over the yolk-sac is a gradual process, and it is in the more peripheral por- tions of the layer that the blood-vessels first make their appearance. They can be distinguished before the split- ting of the mesoderm has been completed, but are always developed in that portion of the layer which is most inti- mately associated with the yolk-sac and consequently becomes the splanchnic layer. The first indication of the vessels is the appearance in the peripheral portion of the mesoderm of cords or minute patches of spherical cells (Fig. 1 20, A ) . These increase in size by the division of the cells and by their separation from one another (Fig. 1 20, B), a--clear fluid appearing in the intervals which separate them. Soon the cells surrounding each cord arrange 240 THE BLOOD. 241 themselves to form an enclosing wall, and the cords, in- creasing in size, unite together to form a network of ves- sels in which float the spherical cells which may now be known as erythrocytes. Viewed from the surface at this stage a portion of the vascular area of the mesoderm would have the appearance shown in Fig. 121, revealing a dense network of canals in which, at intervals, are groups of erythrocytes adherent to the walls, constituting what Fig. 120. — Transverse Section 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 Stricht.) have been termed the blood-islands, while in the meshes of the network unaltered mesoderm cells can be seen, form- ing the so-called substance-islands. At the periphery of the vascular area the vessels ar- range themselves to form a sinus terminalis enclosing the entire area, and the vascularization of the splanchnic mesoderm gradually extends toward the embryo. Reach- ing it, the vessels penetrate the embryonic tissues and eventually come into connection with the heart which has 242 THE DEVELOPMENT OF THE HUMAN BODY. already differentiated and has begun to beat before the connection with the vessels is made, so that when it is made, the circulation is at once established. Before, however, the vascularization reaches the embryo some of the canals begin to en- large (Fig. 122, A), pro- ducing arteries and veins, the rest of the network forming capillaries unit- ing these two sets of vessels, and, this process continuing, there are eventually differentiated a single omphalo-mesen- teric (vitelline) artery and two omphalo - mesenteric (■vitelline) veins (Fig. 122, B). In the human embryo the small size of the yolk-sac permits of the extension of the vascu- lar area over its entire surface at an early pe- riod, and this condition has already been reached in the earliest stages known and consequently no sinus terminalis such as occurs in the rabbit is visible. Otherwise the conditions are probably similar to what has been described above, the first circulation de- veloped being associated with the yolk-sac. The Formation of the Blood. — The erythrocytes, which Fig. 121. — Surface View op a Por- tion of the Area Vasculosa of a Chick. The vascular network is represented by the shaded portion. Bi, Blood-island ; Si, substance-island. — (Disse.) THE BLOOD. 243 are the first blood-eorpuscles, are all nucleated and are for a time the only cells occurring in the blood, though later other cells, arising in tissues exterior to the blood-vessels, make their way into the vessels, forming leukocytes. From their very first formation then the red (erythrocytes) and white (leukocytes) blood-corpuscles have a different ori- gin, and they remain distinct throughout life, one form never becoming converted into the other. * Erythrocytes in the liver substance the blood, and in the haematopoietic organs they may be observed in active mitosis. In addition other cells, having the same general appearance as the erythocytes but lacking haemoglobin, also occur, and these, which may be termed A erythroblasts, produce by division erythrocytes in which haemoglobin gradu- Fig. 124.— Stages in the Irans- & ° formation of an Erythrocyte ally appears. After the sec- intoan Erythropeastid. -{van d , how a third der Stncht.) ' ' form of blood-elements ap- pears in the form of non-nucleated discs containing haemo- globin, and these may be termed erythroplastids. They are derived from the erythrocytes, whose nuclei, originally and in a capillary; //, hepatic cells. - {van der Stricht.) 246 THE DEVELOPMENT OF THE HUMAN BODY. reticular in structure, gradually condense to become spheri- cal, deeply staining masses, and are finally completely extruded from the cytoplasm (Fig. 124). The cast-off nuclei undergo degeneration and phagocytic absorption by the leukocytes, and the masses of cytoplasm pass into the circulation, becoming more and more numerous as development proceeds, until finally they are the only haemo- globin-containing elements in the blood and form what are properly termed the red blood-corpuscles. In the later fetal and the post-natal stages erythrocytes are to be found only in the red bone-marrow. In the formation of the new leukocytes there is a ten- dency for the dividing cells to collect in more or less defi- nite groups which have been termed germ-centers (Flem- ming). The new cells when they first pass into the cir- culation have a relatively large nucleus surrounded by a small amount of cytoplasm, and, since they resemble the cells found in the lymphatic vessels, are termed lympho- cytes. In the circulation the nuclei become larger and the cytoplasm more voluminous and amoeboid, the cells being then known as mononuclear leukocytes, and transitional forms lead from these to still larger cells with irregularly lobed or branched nuclei, the polymorphonuclear leuko- cytes, while these again seem to lead to polynuclear cells. It is probable that these various kinds of cells stand in genetic relation to one another, the polymorphonuclear and polynuclear forms perhaps representing the com- mencement of the degeneration and breaking down of the elements. In the fetal haematopoietic organs and in the bone-mar- row 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-cor- puscles. These giant-cells as they occur in the bone- THE BLOOD. 247 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 osteo- clasts (p. 180). In the other kind (Fig. 125) the nucleus is single, but it is large and irregular in shape, frequently appearing as if it were producing buds. These mega- caryocytes appear to be phagocytic cells, having as their Fig. 125. — Portion of a Section from the Liver of an Embryo Cat of 2.7 mm. showing a Megacaryocyte Surrounded by Erythro- cytes in a Blood-vessel. — {Howell.) function the destruction of degenerated corpuscles and of the nuclei of the erythrocytes. Little is certainly known as yet as to the origin of the blood-platelets, though the most plausible suggestion is that they are- the fragmented nuclei of broken-down leukocytes. The question of the origin of the various forms of blood- elements is a very difficult one, and the opinions of some ob- servers are very different from some of the statements made above. Thus it has been maintained that the nuclei of the 248 THE DEVELOPMENT OF THE HUMAN BODY. erythrocytes are not extruded in the formation of erythro- plastids, but undergo a degeneration within the original cell; that mesenchyme cells of the marrow become transformed into leukocytes; that the polymorphonuclear and polynuclear leukocytes are not stages leading to disintegration, but represent stages of amitotic division, etc. It is impossible in the limits of the present work to discuss these various ideas and the views which have seemed to be most strongly supported by observations have been chosen for presentation. The Formation of the Heart. — The heart makes its ap- pearance 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 line. On each side of the body near the margins of the embry- onic area a fold of the splanchnopleure appears projecting into the coelomic cavity and within this fold a very thin- walled sac is formed, probably by a splitting off of its in- nermost cells (Fig. 126, A). Each fold will produce a portion of the muscular walls (myocardium) of the heart, and each sac part of its endothelium (endocardium). As the constriction of the embryo from the yolk-sac proceeds, the two folds are gradually brought nearer together (Fig. 1 26, B), until they meet in the mid- ventral line, when the myocardial folds and endocardial sac fuse together (Fig.. 126, C) to form a cylindrical heart lying in the mid- ventral line of the body, in front of the anterior surface of the yolk- sac and in what will later be the cervical region of the body. At an early stage the various veins which have already been formed, the omphalo-mesenterics.umbilicals, jugulars, 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 con- tinued forward on the ventral surface of the pharyngeal region and carries the blood away from the heart. The THE HEART. 249 blood accordingly opens into the posterior end of the heart tube and flows out from its anterior end. en Fig. 126. — 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; /;, heart; ;', digestive tract. — (After Strahl and Carius.) The simple cylindrical form soon changes, however, the heart tube in embryos of 2.15 mm. in length having be- 21 250 THE DEVELOPMENT OF THE HUMAN BODY. come bent upon itself into a somewhat S-shaped curve (Fig. 127). Dorsally and to the left is the lower 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 downward and to the right, where it again bends at first dorsally and then anteriorly to pass over into the aortic bulb. The portion of the curve which Fig. 127. — Heart of Embryo op 2.15 mm., from a recon- struction. a, Auricle ; ab, aortic bulb ; d, diaphragm ; dc, ductus Cuvieri ; I, liver; v, ventricle ; vj, jugu- lar vein; vu, umbilical vein. —{His.) Fig. 128. — Heart of Embryo of 4.2 mm. seen from the Dorsal Surface. DC, Ductus Cuvieri ; I A, left auricle ; rA, right auricle ; vj, jugular vein ; VI, left ventricle; vu, umbilical vein. — (His.) lies dorsally and to the left is destined to give rise to both auricles, the portion which passes from right to left repre- sents the future left ventricle, while the succeeding portion represents the right ventricle. In later stages (Fig. 128) the left ventricular portion drops downward in front of the auricular portion, assuming a more horizontal posi- tion, while the portion which represents the right ven- THE HEART. 251 tricle 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 auricular part of the heart and form the first indica- tions of the two auricles. As development progresses, these increase in size to form large pouches opening into a common auricular canal (Fig. 129) which is directly con- tinuous with the left ventricle, and as the enlargement of the pouches continues their openings into the canal en- large, until finally the pouches become contin- uous with one another, forming a single large sac, and the auricular canal becomes reduced to a short tube which is slightly invaginated into the ventricle (Fig. 130). In the mean time the sinus venosus, which was originally an oval sac and opened into the au- ricular canal, has elon- gated transversely until it has assumed the form of a crescent whose convexity is in contact with the walls of the auricles, and its opening into the heart has verged toward the right, until it is situated entirely within the area of the right auricle. As the enlargement of the auricles continues, the right horn and median portion of the crescent are gradually taken up into their walls, so that the various veins which origi- nally opened into the sinus now open directly into the right auricle by a single opening, guarded by a projecting fold which is continued upon the roof of the auricle as a Fig. 129. — Heart of Embryo of 5 mm., Seen from in Front and Slightly from Above. — (His.) ?5- THE DEVELOPMENT OF THE HUMAN BODY. muscular ridge known as the septum spurium (Fig. 130, sp). The left horn of the crescent is not taken up into the auricular wall, but remains upon its posterior surface as an elongated sac forming the coronary sinus. The division of the now practically single auricular cav- ity into the permanent right and left auricles begins with the formation of a falciform ridge running dorso-ventrally Fig. 130. — Inner Surface op the Heart of an Embryo of 10 mm. al, Auriculo-ventricular thickening; sp, septum spurium; ss, septum primum; sv, septum ventrieuli; ve, Eustachian valve. — (His.) across the roof of the cavity. This is the auricular septum or septum primum (Fig. 130, ss), and it rapidly increases in size and thickens upon its free margin which reaches almost to the upper border of the short auricular canal (Fig. 132). The continuity of the two auricles is thus almost dissolved, but is soon re-established by the forma- tion in the dorsal part of the septum of an opening which THE HEART. 253 Si St. soon reaches a considerable size and is known as the fora- men ovale (Fig. 131, fo). Close to the auricular septum, and parallel with it, a second ridge appears in the roof and ventral wall of the right auricle. This septum secundum (S 2 ) is from the beginning very much thicker than the auricular septum, and its free end, arching around the ventral edge and floor of the foramen ovale, becomes con- tinuous with the left lip of the fold which guards the opening of the sinus venosus and with this forms the annulus of Vieus- sens of the adult heart. When the absorption of the sinus venosus into the wall of the right auricle has proceeded so far that the veins communi- cate directly with the auricle, the vena cava superior opens into it at the upper part of the dorsal wall, the vena cava in- ferior 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 spu- rium, gradually disappears; the lower portion persists, however, and forms ( 1 ) the Eustachian valve (Fig. 131, 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 opening of the coro- nary sinus. At first no veins communicate with the left auricle, but on the development of the lungs and the es- Fig. 131. — Heart of Em- bryo op 10.2 CM. FROM which Half of the Right Auricle Has Been Re- moved. jo, Foramen ovale; pa, pul- monary artery; S lt septum primum ; S 2 , septum secun- dum; Sa, systemic aorta; V, right ventricle; vci, and vcs, inferior and supe- rior venae cavse; Ve, Eus- tachian valve. 254. THE DEVELOPMENT OF THE HUMAN BODY. tablishment 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 auricle (Fig. 132, Vep)-. As is the case with the right auricle and the sinus venosus, the expansion of the left auricle brings about the absorption of the short single trunk into its walls, and, the expansion continuing, the two vessels are also absorbed, so that eventually the four primary veins open independently into the auricle. While the auricular septa have been developing there has appeared on the dorsal wall of the auricular canal a tu- bercle-like thickening of the endocardium, and a similar thickening also forms on the ventral wall. These endo- cardial cushions increase in size and finally unite together by their tips, forming a complete partition dividing the auricular canal into a right and left half (Fig. 132). With the upper edge of this partition the thickened lower edge of the auricular septum unites, so that the separa- tion of the auricles would be complete were it not for the foramen ovale. While these changes have been taking place in the au- ricular portion 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 ventricu- lar cavity along the line of junction of the right and left portions a ridge, composed largely of muscular tissue, arises (Figs. 130 and 132), 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 auricular canal. Ventrally, however, the ridge, known as the ven- tricular septum, fails to reach the ventral part of the par- tition, so that an oval foramen, situated just below the THE HEART. 255 point where the aortic bulb arises, still remains between the two ventricles. This opening is finally closed by what SM En.s En. r Bw 2 Fig. 132. — Section through a Reconstruction op the Heart of a Rabbit Embryo op 10.1 mm. Ad and Ad lt Right, and As, left auricle; Bw 1 and Bw 2 , lower ends of the ridges which divide the aortic bulb; En, endocardial cushion; En.r and En.s, thickenings of the cushion; la, interauricular and Iv, interventricular communication ; s lt septum primum ; Sd, right and Ss, left horn of the sinus venosus; S.iv, ventricular septum; SM, opening of the sinus venosus into the auricle; Vd, right and Vs. left ventricle ; Vej, jugular vein ; Vep, pulmonary vein ; Vvd and Vvs, right and left limbs of the valve guarding the opening of the sinus venosus. — (Born.) 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 256 THE DEVELOPMENT OF THE HUMAN BODY. p. 264) arise, and is formed by the fusion of the free edges of two 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 sepa- ration of the two ventricles (Fig. 133). The bulb now con- sists of two vessels lying side by side, and owing to the po- sition of the partition at its anterior end, one of these vessels, that which opens into the right ventricle, is con- tinuous 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 con- tinuation of the bulb. As soon as the development of the partition is completed, two grooves, corresponding in position to the lines of attachment 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 mus- cle bundles which compose the wall of the ventricle are very loosely arranged, so that the ventricle is a somewhat spongy mass of muscular tissue with a relatively small cavity. As development proceeds the bundles nearest the outer surface come closer together and form a compact layer, those on the inner surface, however, retaining their loose arrangement for a longer time (Fig. 132). The lower edge of the auricular 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 ad- ditional flap arises on each side from the lower edge of the partition of the auricular canal, so that three flaps occur in the right auriculo- ventricular opening and two in the left. To the under surfaces of these flaps the loosely Fav.d S.ivr Fig. 133. — Diagrams ok Sections through the Heart of Embryo Rabbits to show the Mode of Division of the Ventricles and of the Auriculo-ventricular Orifice. Ao, Aorta; Ar.p, pulmonary artery; B, aortic bulb; Bw 2 , one of the ridges which divide the bulb; Eo and Eu, upper and lower thicken- ings of the margins of the auriculo-ventricular orifice; F.av.c, the original auriculo-ventricular orifice; F.av.d and F.av.s, right and left auriculo-ventricular orifices; Oi, interventricular communica- tion; S.iv, ventricular septum; Vd and Vs, right and left ventricles. 22 257 2^8 THE DEVELOPMENT OF THE HUMAN BODY. arranged muscular trabecular of the ventricle are attached , and muscular tissue also occurs in the flaps. This condi- tion is transitory, however; the muscular tissue of the flaps degenerates to form a dense layer of connective tis- sue, and at the same time the muscular trabecular undergo a condensation. Some of them separate from the flaps, which represent the auriculo-ventricular valves, and form muscle bundles which may fuse throughout their entire length with the more compact portions of the ventricular walls, or else may be attached only by their ends, form- ing loops ; these two varieties of muscle bundles constitute Fig. 134. — Diagrams showing the Development of the Auriculo- ventricular Valves. b, Muscular trabecular; cht, chords tendinese; mk and mk l , valve; pm, musculus papillaris ; tc, columnar carneae ; v, ventricle. — (From Hertwig, after Gegenbaur.) the columnce carneoz of the adult heart. Other bundles may retain a transverse direction, passing across the ven- tricular cavity and forming the so-called moderator bands; while others, again, retaining their attachment to the valves, condense only at their lower ends to form the mus- culi papillares, their upper portions undergoing conversion into strong though slender fibrous cords, the chordae ten- dinece (Fig. 134). The endocardial lining of the ventricles is at first a sim- ple sac separated by a distinct interval from the myocar- THE HEART. 259 dium, but when the condensation of the muscle trabecular occurs the endocardium applies itself closely to the irregu- lar surface so formed, dipping into all the crevices between the columnse carnese and wrapping itself around the mus- culi papillares and chordae tendineae so as to form a com- plete lining of the inner surface of the myocardium. The aortic and pulmonary semilunar valves make their appearance, before the aortic bulb undergoes its longitu- dinal splitting, as four tubercle-like thickenings of con- nective tissue situated on the inner wall of the bulb just where it arises from the ventricle. When the di- vision of the bulb occurs, two of the thickenings, situated on oppo- site sides, are divided, so that both the pulmonary and systemic aorte receive three thickenings ft * ^^H£l (Fig. 135). Later the thickenings mation op the Semi- become hollowed out on the sur- ^nbcmr.) faces directed away from the ven- tricles and are so converted into the pouch-like valves of the adult. Changes in the Heart after Birth. — The heart when first formed lies far forward in the neck region of the embryo, * between the head and the anterior surface of the yolk-sac, and from this position 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 change. For at an early stage the ventricles lie directly in front of (i. e. , ventrad to) the auricles and not below them as in the adult heart, and this primitive con- dition is retained until the diaphragm has reached its final position (see p. 342). In addition to these changes in position, important 260 THE DEVELOPMENT OF THE HUMAN BODY. changes also occur in the auricular septum after birth. Throughout the entire period of fetal life the foramen ovale persists, permitting the blood returning from the placenta and entering the right auricle to pass directly across to the left auricle, thence to the left ventricle, and so out to the body through the systemic aorta (see p. 288). At birth the lungs begin to function and the placental circulation is cut off, so that the right auricle 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 mixture 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 auricular septum which is between the edge of the foramen ovale and the dorsal wall of the auricle increases in width, so that the foramen is carried further and fur- ther away from the dorsal wall of the auricle and comes to be almost completely overlapped by the annulus of Vieus- sens (Fig. 131). This process continuing, the dorsal por- tion of the auricular septum finally overlaps the free edge of the annulus, and after birth the fusion of the overlap- ping surfaces takes place and the foramen is completely 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 auricles. This, however, does not allow of any mingling of the blood in the two cavities, since when the auricles contract the pressure of the blood on both sides will force the overlapping folds to- gether and so practically close the opening. Occasionally the growth of the dorsal portion of the septum is imperfect or is inhibited, in which case closure of the foramen ovale is im- possible. THE ARTERIES. 26l The Development of the Arterial System. — It has been seen that the formation of the blood-vessels begins in the extra-embryonie splanchnic mesoderm surrounding the Fig. 136. — Reconstruction of Embryo of 2.6 mm. am, Amnion; B, belly-stalk; E, optic evagination; H, heart; Mn, mandi- bular process; 0, auditory capsule; om, omphalo-mesenteric vein; v, umbilical vein; Y, yolk-stalk. — (His.) yolk-sac and extends thence toward the embryo. The two original omphalo-mesenteric arteries, entering the body of the embryo along the yolk-stalk, make their way to the dorsal wall of the abdomen, and growing forward 262 THE DEVELOPMENT OF THE HUMAN BODY. /KiV and backward give rise to two longitudinal stems, the representatives of the dorsal aorta. From near the pos- terior ends of these there arise at an early stage two branches, which pass out along with the allantois into the belly-stalk and so to the chorionic villi, forming the allan- toidean or umbilical arteries, while anteriorly each aorta sends branches ventrally in the anterior branchial arches and these, uniting together, pass backward along the floor of the pharynx to become con- tinuous with the aortic bulb (Fig. 136). Later the two dorsal aortae fuse together as far for- ward as the region of the eighth cervical segment to form a single trunk (Fig. 137), and the left omphalo-mesenteric ar- tery disappears, the right one persisting to form the superior mesenteric artery of the adult. It will be convenient to consider first the his- tory of the vessels which pass ventrally in the branchial arches. Altogether, six of these vessels are developed, the fourth branchial arch possessing a rudimentary one in addition to that which properly belongs to it (Zimmermann), and when fully formed they have an arrangement which may be understood from the diagram (Fig. 137), in which the Fig. 137. — Diagram Illustrating the Arrangement op the Bran- chial Vessels. ab, Aortic bulb ; da, dorsal aorta ; I to VI, branchial arch vessels. THE ARTERIES. 263 vessels are represented as spread out upon a plane surface, the lateral trunks being the dorsal aortae. This arrange- ment, represents a condition which is permanent in the lower vertebrates. In the fishes the respiration is per- formed 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 aortae, which distribute it to the body. But in terrestrial animals, with the loss of the 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 dia- gram resulting. But this condition is merely temporary in the mamma- lia and numerous changes occur in the arrangement of the vessels before the adult plan is realized. The first change is a disappearance of the vessel of the first arch, the ven- tral 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 rep- resents the internal maxillary artery, and possibly also a second branch which represents the facial (His). A little later the second branchial vessel also degenerates (Fig. 138), 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 connection 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, be- comes the external carotid, and the portion which in- 264 THE DEVELOPMENT OF THE HUMAN BODY. tervenes between the third and fourth vessels becomes the common carotid (Fig. 139). The rudimentary fifth vessel, like the first and second, disappears, 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 the lungs, and the portion of the vessel of the right side which intervenes between this Fig. 138.— Arterial System of an Embryo op 10 mm. Ic, Internal carotid; P, pulmonary artery; Ve, vertebral artery; 777 to VI, persistent branchial vessels. — (His.) and the aortic arch disappears, while the corresponding portion of the left side persists until after birth, forming the ductus arteriosus (ductus Botalli) (Fig. 139). When the longitudinal division of the aortic bulb occurs, the septum is so arranged as to place the sixth arch in commu- nication with the right ventricle and the remaining vessels in connection with the left ventricle, the only direct com- munication between the systemic and pulmonary vessels / THE ARTERIES. 265 being by way of the ductus arteriosus, whose significance will be explained later (p. 290). One other change is still necessary before the ves- sels acquire the ar- rangement which they possess during fetal life, and this consists in the disappearance of the lower portion of the right aortic arch (Fig. 139), so that the left arch alone forms the connection be- tween the heart and the dorsal aorta. The upper part of the right aortic arch persists to form the proximal part of the right sub- clavian artery, the portion of the ventral trunk which unites the arch with the aortic bulb becoming the brachio-cephalic (in- nominate) artery. From the entire length of the thoracic aorta, and in the embryo from the aor- tic arches, lateral Fig. 139. — Diagram Illustrating the Changes in the Arrangement of the Branchial Arch Vessels. The broken lines indicate portions of the original vessels which have disappeared. A, Aorta; A A, aortic arch; DA, ductus arteriosus; EC, external carotid; IC, internal carotid ; IM, internal maxillary ; L, lingual; P, pulmonary artery; PA, pulmonary aorta; SA, systemic aorta; Sc, subclavian ; I to VI, original branchial arch vessels. branches arise corresponding to each segment and ac- companying the segmental nerves. The first of these branches arises just below the point of union of the ves- 266 THE DEVELOPMENT OF THE HUMAN BODY. sel of the sixth arch with the dorsal trunk and accom- panies the hypoglossal nerve (Fig. 140, h), and that which accompanies the seventh cervical nerve arises just above the point of union of the two aortic arches (Fig. 140, 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 ar- teries are formed, the fifth lumbars being rep- resented by two large branches, the common iliacs, which seem from their size to be the con- tinuations of the aorta rather than branches of it. The t true continua- tion of the aorta is, how- ever, the art . sacra media, which represents in a de- generated form the caudal prolongation of the aorta of other mammals, and, like this, gives off lateral branches corresponding to the sacral segments. * 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. 140). Fig. 140. — Diagram showing the Re- lations os the Lateral Branches to the Aortic Arches. EC, External carotid ; h, lateral branch accompanying the hypoglossal nerve ; IC, internal carotid ; ICo, intercostal ; JM , internal mammary ; s, sub- clavian; v, vertebral; I to VIII, lateral cervical branches; 1, 2, lateral thoracic branches. THE ARTERIES. 267 In addition to the segmental lateral branches arising from the aorta, visceral branches, which have their origin rather from the ventral surface than the sides, also occur. The development of these branches has as yet been but little studied, but it seems probable that they too may show, when their embryonic history has been worked out, a more perfect segmental plan than is discernible from their adult arrangement. The earliest representative of them is the superior mesenteric artery, whose origin from the left om- phalo-mesenteric has already been described. Several other visceral branches occur both in the thoracic and abdominal re- gions, but they are irregular in their distribution, the unpaired branches of the abdominal re- gion having probably condensed from an original segmental con- dition to form compound trunks such as the cceliac axis and the inferior mesenteric. One pair of the visceral branches, the umbilical arteries, require more than a passing notice on account of their em- bryonic importance. They are formed at a very early stage and arise by a short common trunk from the anterior surface of the aorta (Fig. 141, U 1 ). They pass directly forward on the medial side of the Wolffian duct (see p. 361 ) to the terminal portion of the intestine, and thence pass out along the sides of the allantois to the chorionic villi. Later there are formed from the aorta just below the origin Fig. 141. — Diagram Illus- trating the Development of the Umbilical Arter- ies. A, Aorta; CI I, common iliac; Ell, external iliac; III, in- ternal iliac; V, umbilical artery; U l , the primary proximal and £/ 2 ,the secon- dary proximal part of the umbilical ; vid, Wolffian duct. 268 THE DEVELOPMENT OF THE HUMAN BODY. of the umbilicals, the lateral branches (c.il) which be- come the common iliacs, and from each of these a short branch (U 2 ) arises which passes to the outer side of the Wolffian duct and unites with the umbilical arteries, whereupon the original proximal portions of these arteries disappear and they come to arise from the iliacs instead of directly from the aorta. At birth the portions of the arte- ries beyond the umbilicus are severed when the umbilical cord is cut, and their intra-embryonic portions, which have been called the hypogastric arteries, quickly undergo a reduction in size. The proximal portion of the allantois persists as the urinary bladder, and the proximal portions of the hypogastric arteries remain functional as the supe- rior vesical arteries carrying blood to this viscus, but the portions which intervene between the bladder and- the umbilicus become reduced to solid cords forming the ob- literated hypogastric arteries of adult 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 lateral, segmentally arranged somatic branches and ventral visceral branches whose segmental arrangement is less distinct. With the exception of the aortic trunks (together with their anterior continuation, the internal carotids) and the external carotids, no longitudinal arte- ries exist primarily. In the adult, however, several longi- tudinal 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 dor- THE ARTERIES. 269 sal aorta gives off a twig which passes forward to anas- tomose with a backwardly directed twig from the next Av.c.b. ISp.G. v.cr. Fig. 142. — The Development of the Vertebral Artery in a Rabbit Embryo op Twelve Days. JIIA.B to VI A. 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. — (Hochsteller.) 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 27O THE DEVELOPMENT OF THE HUMAN BODY. 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 links are added from each of the succeeding cervical lateral branches as far back as the seventh (Figs. 142 and 140). But in the mean time the recession of the heart toward the Fig. 143. — Embryo of 13 mm. showing the Mode of Development op the Internal Mammary and Deep Epigastric Arteries. — (Mall.) thorax has begun, with the result that the common carotid stems are elongated and the aortic arches are apparently- shortened so that the subclavian arises on the left side almost opposite the point where the aorta was joined by the sixth branchial vessel. As this apparent shortening proceeds, the various lateral branches which give rise to the chain of anastomoses, with the exception of the THE ARTERIES. 27 I seventh, disappear in their proximal portions 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 lies 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 connection with the dorsal aorta, and, sending off anteriorly and posteriorly anastomosing twigs, develop a short longitudinal stem, the superior intercostal, which opens into the subclavian. The intercostals and their abdominal representatives, the lumbars and iliacs, also give rise to longitudinal anas- tomosing twigs near their ventral ends (Fig. 143), and these increasing in size give rise to the internal mammary and deep epigastric arteries, which together form con- tinuous stems extending from the subclavians to the exter- nal iliacs in the ventral abdominal walls. The superficial epigastrics and other secondary longitudinal vessels are formed in a similar manner. The Development of the Arteries of the Limbs. — Much information is still required before the complete history of the development of the arteries of the limbs can be written, and at present one must rely largely upon the facts of comparative anatomy and on the anomalies which occur in the human body for indications of what the early development is likely to be. So far as embryological ob- servations go, they confirm the conclusions derived from such sources. Notwithstanding the fact that the limbs are formed by outgrowths from several segments, there is as yet no evi- dence to show that a corresponding number of segmental arteries take part in the development of their blood-sup- ply, but it seems that in both limbs the entire arterial sys- 272 THE DEVELOPMENT OF THE HUMAN BODY. tem is formed from a single lateral branch, that of the upper limb, the subclavian, corresponding to the seventh cervical segment, while that of the lower limb, the com- mon iliac, is probably the fifth lumbar branch. In the simplest arrangement the subclavian is continued as a single trunk along the axis of the anterior limb as far as the carpus, where it divides into digital branches for the fingers. In its course through the forearm it lies in the interval between the radius and ulna, resting on the inter- osseous 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 little below the elbow-joint. This may be termed the arteria mediana, and as it develops the arteria interossea gradually dimin- ishes in size, becoming finally the small anterior interosse- ous artery of the adult (Fig. 144), 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 median which forms the arteria ulnaris, and this, passing down the ulnar side of the forearm, unites at the wrist with the 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, the arteria comes nervi mediani, and at the same time there develops from the brachial, at about the middle of the upper arm, what is known as the arteria radialis superficialis (Fig. 144, 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 sur- face of the hand to form the aa. dorsalis pollicis and dor- salis indicis. At first this artery takes no part in the for- THE ARTERIES. 273 mation 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 perforating branch develops which passes between the first and second Fig. 144. — Diagrams showing an Early and a Late Stage in the Development op the Arteries of the Arm. b, Brachial ; i, interosseous ; to, comes nervi mediani ; r, radial ; r s, superficial radial; u, ulnar. 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 a branch (Fig. 144, r) which passes downward and outward to unite with the superficial radial, where- 23 274 THE DEVELOPMENT OF THE HUMAN BODY. upon the upper portion of that artery degenerates until it is represented only by a branch to the biceps 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 stages described above, what is described, for in- stance, as the high branching of the brachial being the per- sistence of the superficial radial. In the leg there is a noticeable difference in the arrange- ment 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 differ- ence is apparently secondary, but, as in the case of the upper limb, it is necessary to rely largely on the facts of comparative anatomy and on anomalies which occur in the human body for an idea of the probable development of the arteries of the lower limb. It has already been seen that the common iliac artery is to be regarded as a lateral branch of the dorsal aorta, and in the simplest condition of the limb arteries its continuation, the anterior division of the internal iliac, passes down the leg as a well-devel- oped sciatic artery as far as the ankle (Fig. 145, s). At the knee it occupies the position of the popliteal of adult anatomy, and below the knee gives off a branch corre- sponding to the anterior tibial (at) which, passing for- ward to the extensor surface of the leg, quickly loses itself in the extensor muscles. The main artery continues downward on the interosseous membrane, and some dis- tance above the ankle divides into a strong anterior and a weaker posterior branch ; the former perforates the mem- brane and is continued down the extensor surface of the leg to form the lower part of the anterior tibial and the dorsalis pedis arteries, while the latter, passing upon the THE ARTERIES. 275 plantar surface of the foot, is lost in the plantar muscles. At this stage the external iliac is a secondary branch of the common iliac, being but poorly developed and not extend- ing as far as the knee. In the second stage the external iliac artery increases in size until it equals the sciatic, and it now penetrates the f 6^ *fi pe f at n pe h pt Fig. 145. — Diagrams Illustrating Stages in the Development op the Arteries of the Leg. at, Anterior tibial; dp, dorsalis pedis; /, femoral; p, popliteal; pe, peroneal; pt, posterior tibial; s, sciatic; sa, saphenous. adductor magnus muscle and unites with the popliteal portion of the sciatic. Before doing this, however, it gives off a strong branch (sa) which accompanies the long saph- enous nerve down the inner side of the leg, and passing be- hind the internal malleolus extends upon the plantar sur- 276 THE DEVELOPMENT OF THE HUMAN BODY. face of the foot, where it gives rise to the digital branches. From this arrangement the adult condition may be de- rived by the continued increase in size of the external iliac and its continuation, the femoral (/), accompanied by a reduction of the upper portion of the sciatic and its separation from its popliteal portion (p). The continua- tion of the popliteal down the leg is the peroneal artery (pe) and the upper perforating branch of this unites with the lower one to form a continuous anterior tibial, the lower connection of which with the peroneal persists in part as the anterior peroneal artery. A new branch arises from the upper part of the peroneal and passes down the back of the leg to unite with the lower part of the arteria saphena, forming the posterior tibial artery (pt), and the upper part of the saphenous becomes much re- duced, persisting as the superficial branch of the anas- tomotica magna (arteria musculo-articularis) and a rudi- mentary chain of anastomoses which accompany the long saphenous nerve. The Development of the Venous System. — The earliest veins to develop are those which accompany the first- formed arteries, the omphalo-mesenterics and umbilicals, 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 longi- tudinal trunks, the anterior and posterior cardinal veins, into which lateral branches, arranged more or less seg- mentally, open. The anterior cardinals appear somewhat earlier than the posterior and form the internal jugular veins of adult anatomy. They are formed by the union of two stems which convey the blood from the brain. One of these stems is formed by a number of veins which pass backward over the surface of the fore-brain, uniting to THE VEINS. 277 form a stem which follows the course of the facial nerve and unites with the other stem formed by veins from the more posterior portions of the brain and passing outward and downward along with the vagus nerve. The various veins of the fore-brain region later condense to form the superior longitudinal sinus (Fig. 146, sss) , while the stem which they formed becomes the lateral sinus (str), with which the ophthalmic vein (yo) unites. A communication, passing on the median side of the ear capsule, develops between the lateral sinus and the posterior stem, and the original communication disappears, the condition repre- sented in Fig. 146, B, being thus acquired. In later stages, as the fore-brain vesicles grow backward, the point of union of the superior longitudinal sinus with the laterals is brought nearer to its adult position, and, at the same time, the portion of the lateral sinus between the com- munication of the ophthalmic vein and the jugular fora- men diminishes in length until it is practically obliterated, the ophthalmics and lateral sinuses meeting at the jugular foramen. The intra-cranial portions of the ophthalmic veins form the cavernous and inferior petrosal sinuses, the superior petrosals being formed later by a communica- tion between the cavernous and lateral sinuses. Passing backward from the jugular foramen the internal jugular veins unite with the inferior cardinals to form on each side a common trunk, the ductus Cuvieri, and then passing transversely toward the median line open into the sides 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 upper- most 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 cervi- .» ;r Fig. 146. — Reconstruction of the Head Veins of Guinea-pig Em- bryos. A, Eye; G, auditory capsule; sss, superior longitudinal sinus; str, lateral sinus ; vja, facial vein ; vj and vji, internal jugular vein ; vje, external jugular vein; vo, ophthalmic vein. — (Salzer.) 278 THE VEINS. 279 cal lateral veins shift their communication from the car- dinals to the jugulars, until, when the subclavians have thus shifted, the jugulars become much larger than the cardinals. When the sinus venosus is absorbed into the wall of the right auricle, the course of the left Cuvierian duct becomes a little longer than that of the right, and from the left jugular, at the point where it is joined by the left subclavian, a branch arises which extends obliquely Fig. 147. — Diagrams showing the Development of the Superior Vena Cava. a, Right 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, inferior and superior vens cavs. across to join the right jugular, forming the left innomi- nate, vein. When this is established, the connection be- tween the left jugular and Cuvierian duct is dissolved, 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 Cuvier- ian duct, thus becomes the superior vena cava. The left Cuvierian duct persists, forming with the left horn of the sinus venosus the coronary sinus. 28o THE DEVELOPMENT Of THE HUMAN BODY. 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 skull along with the fifth nerve and communicates with the in- ternal jugular system, but later this original communica- tion is broken and the facial vein, uniting with other superficial veins, passes over the jaw and extends down the neck as the external jugular (Fig. 146, -vje). Later still the facial 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 disap- pearing 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 primitive condition is retained, but indications of a transference of the intracranial blood to the external jugular are seen in the emissary veins. The inferior cardinal veins, or, as they may more simply be termed, the cardinals, extend backward from their union with the jugulars along the sides of the vertebral column, receiving veins from the mesentery and also 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. 279), the cervical veins shift to the jugulars, as do also the first and second thoracic (inter- costal) veins, but the remaining intercostals, together with the lumbars and sacrals, continue to open into the cardi- nals. In addition, the cardinals receive in early stages the veins from the primitive kidneys (mesonephros), which are exceptionally large in the human embryo, but when they are replaced later on by the permanent kidneys THE VEINS. 28l (metanephros) their 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 cardinals. These veins persist, however, in part until adult life, forming what are known as the azygos and hemi- azygos veins, but the changes by which they acquire their final arrangement are so intimately associated with the development of the inferior vena cava that their descrip- tion may be conveniently postponed until the history of that vein, together with that of the omphalo-mesenteric and of the umbilical veins, has been presented. The omphalo-mesenteric 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 corresponding umbili- cal 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 omphalo-mesenteric veins common trunks which open into the ductus Cuvieri. As the liver develops it comes into intimate relation with the omphalo- mesenteric veins, which receive numerous branches from its substance and, indeed, seem to break up into a network (Fig. 148, A) traversing the liver substance and uniting again to form two stems which represent the original con- tinuations of the omphalo-mesenterics. From the point where the common trunk formed by the right omphalo- mesenteric and umbilical veins opens into the Cuvierian duct a new vein develops, passing downward and to the left to unite with the left omphalo-mesenteric ; this is the ductus venosus (Fig. 148, B, DVA). In the mean time three cross-connections have developed between the two 24 282 THE DEVELOPMENT OF THE HUMAN BODY. omphalo-mesenteric veins, two of which pass ventral and the other dorsal to the intestine, so that the latter is sur- rounded by two venous loops (Fig. 149, A), and a connec- tion is developed between each umbilical vein and the corresponding omphalo-mesenteric (Fig. 148, B), that of the left side being the larger and uniting with the omphalo- mesenteric just where it is joined by the ductus venosus so as to seem to be the continuation of this vessel (Fig. 148, DC, JiC. MK4 JTus Vom.s. Vbjrul. Vo.ms. MVA. KP/:A Kl/J. 148. — Diagrams Illustrating the Transformations op the Omphalo-mesenteric and Umbilical Veins. D.C, Ductus Cuvieri; D.V.A, ductus venosus; V.o.m.d and V.o.m.s, right and left omphalo-mesenteric veins; V.u.d and V.u.s, right and left umbilical veins. — (Hochstetter.) C). When these connections are complete, the upper portions of the umbilical veins degenerate (Fig. 149), and now the right side of the lower of the two omphalo-mesen- teric 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 om- phalo-mesenteric veins the vena porta. THE VEINS. 283 While these changes have been progressing the right umbilical vein, originally the larger of the two (Fig. 148, A and B, V.u.d), has become very much reduced in size and, losing its connection with the left vein at the umbili- cus, forms a vein of the ventral abdominal wall in which the blood now flows from above downward. The left umbilical now forms the only route for the return of Fig. 149. — A, The Venous Trunks of an Embryo op 5 mm. seen from the Ventral Surface; B, Diagram Illustrating the Trans- formation to the Adult Condition. Vcd and Vcs, right and left superior venae cava? ; Vj, jugular vein ; V.om, omphalo-mesenteric vein; Vp, vena porta; Vu, umbilical vein (lower part); Vu 1 , umbilical vein (upper part); Vud and Vus, right and left umbilical veins (lower parts). — (His.) blood from the placenta, and appears to be the direct con- tinuation of the ductus venosus (Fig. 149, C), into which open the hepatic veins, returning the blood distributed by the portal vein to the substance of the liver. Returning now to the cardinal veins, it has been found in the rabbit that the branches which come to them from the mesentery anastomose longitudinally to form a vessel 284 THE DEVELOPMENT OF THE HUMAN BODY. lying parallel 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 corre- sponding 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 right subcardinal which is anterior to the cross-connection now rapidly enlarges and unites with the ductus venosus just where the hepatic veins open into that vessel (Fig. 150, A), and at the same time the lower part of the right cardinal and its connection with the right subcardinal also enlarge, and these three elements straighten out to form a single longitudinal trunk, which, together with the proximal portion of the ductus veno- sus, constitutes the vena cava inferior of the adult. As soon as the establishment of this vessel is accom- plished, the lower portion of the right subcardinal under- goes degeneration, while the left one, diminishing in size, persists as the left suprarenal vein (Hochstetter) (Fig. 150, B, vsr). The cross-branch between the two subcardinals persists, however, and by its connection with the left cardinal allows the blood from the lower part of that vein to flow over into the vena cava. As the permanent kidneys grow forward (see Chap. xiii) they push their way between the aorta and the poste- rior portions of the cardinal veins, forcing the latter off to the side and interfering with the flow of blood in them, a difficulty which is overcome by the development of a branch from each cardinal, just above the kidney, which passes to the medial side of the ureter to unite again with the cardinal below (Fig. 150, B). As soon as this circle THE VEINS. 28S around the ureter has been established, its lateral limb, which represents part of the original cardinal vein, degen- erates, its anterior portion alone persisting to form a part of the renal vein (compare Figs. 150, A and B, r). An anastomosis now develops between the right and left car- dinals at the point where the iliac veins open into them Fig. 150. — Diagrams Illustrating the Development of the Inferior Vena Cava. cs, Coronary sinus; dv, ductus venosus; il, iliac vein; r, renal; scl, sub- clavian; sp, spermatic; ra, vena azygos; vh, hepatic; vha, vena hemi- azygos; vi, left innominate; vj, jugular; vsc, subcardinal; vsr, supra- renal. (Fig. 150, B), and the portion of the left cardinal which intervenes between this anastomosis and the entrance of the spermatic (ovarian) vein disappears, the remainder of it, as far forward as the renal vein, persisting as the upper part of the left spermatic (ovarian) vein, which thus comes to open into the renal vein instead of into the vena cava as 286 THE DEVELOPMENT OF THE HUMAN BODY. does the corresponding vein of the right side of the body (Fig. 1 50, C, sp). 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 prox- imal part of the left renal vein, which consequently receives the left suprarenal (Fig. 150, C). The observations upon which the above description is based have been made most thoroughly upon the rabbit, but it seems probable from the partial observations that have been made that the same 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, con- sisting of at least four elements: (1) the proximal part of the ductus venosus; (2) the anterior part of the right subcardinal; (3) the cross-connection between the right cardinal and subcardinal; and (4) the posterior part of the right cardinal. The fate of the anterior portions of the cardinal veins has yet to be considered. When the large cross-connection with the subcardinals has been established, the portions of the cardinals immediately anterior undergo degeneration, so that their anterior portions become quite disconnected from the posterior (Fig. 150, B). They continue to re- ceive the intercostal veins, and the right one, retaining its connection with the ductus Cuvieri, becomes the vena azygos (Figs. 150, B and C, va), while that on the left side, after developing a cross-connection with its fellow, degen- erates at its anterior end, and, so becoming separated from the ductus Cuvieri, is transformed into the vena hemiazygos of adult anatomy (Fig. 150, B and C, vha). The ascending lumbar veins, frequently described as the commencements of the azygos veins, are in reality secondary formations developed by the anastomoses of anteriorly and posteriorly directed branches of the lumbar veins. THE VEINS. 287 The Development of the Veins of the Limbs. — The devel- opment of the limb veins of the human embryo requires further investigation, 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. The blood brought to the limbs by the arteries is collected into a marginal vein which sur- rounds the free edges of the distal portions of the limb (Fig. 151, A) and passes proximally in two stems, one situated on the ulnar (fibular) and the other on the radial Fig. 151. — The Development op the Arm Veins in the Rabbit. vb, Vena basilica; vc, vena cephalica. It is to be noted that in the rabbit the basilic vein at one stage (C) is much reduced in size, but is later re-established. — (Hochstetter.) (tibial) side. In the anterior extremity the radial vein becomes of less and less importance (Fig. 151, B), and as the digits develop the marginal vein becomes broken up into segments and disappears (Fig. 151, C), while the ulnar vein persists, forming the basilic vein (vb) of adult anatomy, of which the axillary and subclavian veins are the proximal continuation. All other veins of the arm are secondary or tertiary developments, the cephalic (ve) and other superficial veins first developing and later the deep veins (vence comites). At first the cephalic vein, 288 THE DEVELOPMENT OF THE HUMAN BODY. passing over the clavicle, empties into the external jugu- lar, but later it forms a connection with the axillary below the clavicle, the portion abpve this connection persisting as a small vein known as the jugulo-cephalic. In the lower limb the changes are somewhat similar, the tibial and marginal veins disappearing, while the fibular persists as the short saphenous and sciatic veins, which are at first continuous. The anterior tibial and long saphenous are of secondary development, while, as in the arm, the deep veins are the latest to form. On the estab- lishment of these last the short saphenous makes connec- tion with the popliteal, while the sciatic, like the corre- sponding artery, undergoes a marked reduction. The Pulmonary Veins. — The development of the pul- monary veins has already been described in connection with the development of the heart (see p. 254). 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 necessarily somewhat different from what obtains in the child after birth. Taking the placenta as the starting-point, the blood passes along the umbilical vein to enter the body of the fetus at the umbili- cus, whence it passes forward in the free edge of the ante- rior mesentery (see p. 340) until it reaches the liver. Here, owing to the anastomoses between the umbilical and omphalomesenteric veins, a portion of the blood traverses the substance of the liver to open by the hepatic veins into the inferior vena cava, while the remainder passes on through the ductus venosus to the cava, the united streams opening into the right auricle. This blood, whose purity is only slightly reduced by mixture with the blood re- turning from the inferior vena cava, is prevented from passing into the right ventricle by the Eustachian valve, THE FETAL CIRCULATION. 289 which directs it to the foramen ovale, and through this it passes into the left auricle, thence to the left ventricle, and so out by the systemic aorta. da a. pa ypu Fig. 152. — The Fetal Circulation. ao, Aorta; a.pu, pulmonary artery; au, umbilical artery; da, ductus arteriosus; dv, ductus venosus; int, intestine; vci and vcs, inferior and superior vena cava; vh, hepatic vein; vp, vena porta;; v.pu, pulmonary vein; vu, umbilical vein. — {From Kallmann.) The blood which has been sent to the head, neck, and upper extremities is returned by the superior vena cava also into the right auricle, but this descending stream 29O THE DEVELOPMENT OF THE HUMAN BODY. opens into the auricle to the right of the annulus of Vieus- sens (see Fig. 131) and passes directly to the right ventri- cle without mingling to any great extent with the blood returning by way of the inferior cava. From the right ventricle this blood passes out by the pulmonary artery, but the lungs at this period are collapsed and in no condi- tion 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 abdomen 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. It will be perceived that although no portion of the body receives absolutely pure placental blood, yet the quality of that which is supplied to the liver, heart, head, neck, and upper limbs is much better than that distrib- uted by the branches arising from the aorta below the union of the ductus arteriosus. Hence it is that the an- terior portions of the fetus are much better developed than the posterior. 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 arte- riosus diminishes in size as the pulmonary 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 be- comes converted into the round ligament of the liver. THE LYMPHATICS. 2QI The Development of the Lymphatic System. — It has already been seen (p. 243) that the lymphocytes first make their appearance in the tissues surrounding the early blood-vessels, but opinions differ as to their exact origin. According to some observers, they are formed by modifi- cation of mesenchyme cells, while others believe that they have evidence that the lymphocytes of the intestinal and tonsillar lymph-nodes are derived from the intestinal and tonsillar epithelium, and quite recently it has been main- tained that the epithelial cells which form the thymus body in fishes are directly transformed into lymphocytes. Which view will prove correct must be left for future ob- servations to decide. The development of the lymphatic vessels has recently been carefully studied in pig embryos and the results ob- tained have been partially confirmed in human embryos (Sabin). The vessels are first distinguishable in pig em- bryos of 14.5 mm. as two small sacs or lymph hearts, which arise, one on each side, from near the junction of the sub- clavian and jugular veins, the opening of the sac into the veins being guarded by a valve due to the oblique direc- tion taken by the outgrowth. From each lymph heart branches, which anastomose and radiate in all directions, grow outward toward the skin which they reach in em- bryos of about 18 mm., and in later stages continue to extend in a radiating manner until they form a subcu- taneous network over the anterior half of the body. In the mean time the lymph hearts have separated from their points of origin (Fig. 153, A, ALH), with which, however, they remain connected by a duct, and from this a branch grows backward, following the line of the vagus nerve (Fig 153, A, TD). The branch on the left side soon meets with the aorta and, using this as a guide, grows more rapidly than its fellow on the right and becomes the thoracic duct, 2Q2 THE DEVELOPMENT OF THE HUMAN BODY. or, rather, since it divides just before it reaches the aorta and sends a branch backward on either side of that vessel, it gives rise to two thoracic ducts (Fig. 153, B). Fig. 153. — Diagrams showing the Arrangement of the Lymphatic Vessels in Pig Embryos op (A) 20 mm. and (S) 40 mm. ACV, Jugular vein; ADR, suprarenal body; ALH, anterior lymph heart; Ao, aorta; Arm.D, deep lymphatics to. the arm; D, diaphragm ; Du branches to duodenum; FV, femoral vein; H, branches to heart; K, kidney; LegD, deep lymphatics to leg; Lu, branches to lung; MP, branches to mesenteric plexus; CE, branch to oesophagus; PCV cardinal vein; PLH, posterior lymph heart; RC, receptaculum chyh; RLD, right lymphatic duct; ScV, subclavian vein; SV sciatic vein; St, branches to stomach; TD, thoracic duct; WB, Wolffian body. — (Sabin.) THE LYMPHATICS. 293 In embryos of 20 mm. a second pair of lymph hearts develops at the junction of the sciatic veins with the cardi- nals (Fig. 153, A, PLH), and from these branches grow to- ward the surface and radiate subcutaneously, similarly to those from the anterior hearts, with which they eventually unite. The thoracic ducts, continuing to elongate back- ward, dilate opposite the kidneys to form two rcceptacula chyli (Fig. 153, B,RC) and still more posteriorly unite with the posterior lymph hearts, which then separate com- pletely from the veins from which they originated. m Fig. 154.- -Developing Lymphatic Gland from the Axilla of an Embryo of Eleven Weeks. — (Chievitz.) In later stages branches, arising as outgrowths from the thoracic ducts, gradually invade the mesentery and the various organs, following in general the course of the arte- ries, as do also the branches which pass to the limbs to form their deep lymphatics; the superficial branches, on the contrary, follow essentially the course of the veins. The lymph hearts gradually elongate as development proceeds and eventually become undistinguishable from the vessels, and at various points in the system minute plexuses arise, around which the adjacent mesenchyme 294 THE DEVELOPMENT OF THE HUMAN BODY. condenses to form a capsule, the whole constituting a lymph-node (Fig. 154). Up to this stage of the development no valves are pres- ent in the vessels, and the development of these has yet to be studied, as has also the final transformation of the condition described into that found in the adult. It seems probable that in human embryos the two thoracic ducts, together with the receptacula chyli, gradually approach one another and finally fuse throughout their entire length to form the single receptaculum and thoracic duct of the adult. The not infrequent occurrence of a partial doubling of the thoracic duct receives a simple explana- tion if this be the case. LITERATURE. E. van BENEDENand C. Julin: " Recherches sur la formation des annexes foetales chez les mammiferes," Archives de Biolog., v, 1884. A. C. BErnays: " Entwickelungsgeschichte der Atrioventricularklappen," Morphol. Jakrbuch, II, 1876. G. Bqrn: "Beitrage zur Entwicklungsgeschichte des Saugethierherzens," Archill fur mikrosk. Anat., xxxiii, 1889. J. H. Chievitz : "Zur Anatomie einiger Lymphdriisen im erwachsenen und fotalen Zustande," Archiv fur Anat. und Physiol., Anat. Abth., 1881. J. DissE: "Die Entstehung des Blutes und der ersten Gefasse im Huh- nerei," Archiv fur mikrosk. Anat., xvi, 1879. A. C. F. Eternod: "Premiers stades de la circulation sanguine dans l'oeuf et l'embryon humain," Anat. Anzeiger, xv, 1899. W. His: "Anatomie menschlicher Embryonen," Leipzig, 1880-1882. F. Hochstetter: " Ueber die ursprungliche Hauptschlagader der hinteren Gliedmasse des Menschen und der Saugethiere, nebst Bemerkungen iiber die Entwicklung der Endaste der Aorta abdominalis," Morphol. Jahrbuch, xvi, 1890. F. Hochstetter: "Ueber die Entwicklung der A. vertebralis beim Kanin- chen, nebst Bemerkungen iiber die Entstehung der Ansa Vieussenii," Morphol. Jakrbuch, xvi, 1890. F. Hochstetter: "Ueber die Entwicklung der Extremitatsvenen bei den Amnioten," Morphol. Jahrbuch, xvn, 1891. F. Hochstetter: "Beitrage zur Entwicklungsgeschichte des Venensys- tems der Amnioten," Morphol* Jahrbuch, xx, 1893. LITERATURE. 295 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 Func- tion of the Giant-cells of the Marrow," Journ. of Morphol., iv, 1890. F. P. Mall : " Development of the Internal Mammary and Deep Epigastric Arteries in Man," Johns Hopkins Hospital Bulletin, 1898. J. Nusbaum and T. Prymak: "Eur Entwickelungsgeschichte der lym- phoiden Elemente der Thymus bei den Knochenfischen," Anat. An- zeiger, xix, 1901. K. RetterER: "Sur la part que prend 1' epithelium a la formation de la bourse de Fabricius, des amygdales et des plaques de Peyer," Journ. de I' Anat. et de la Physiol., xxix, 1893. C. Rose: " Zur Entwicklungsgeschichte des Saugethierherzens," Morphol. Jahrbuch, xv, 1889. H. SalzER: "Ueber die Entwicklung der Kopfvenen des Meerschwein- chens," Morphol. Jahrbuch, XX, 1893. P. Stohr : "Ueber die Entwicklung der Darmlymphknotchen und iiber die Ruckbildung von Darmdriisen," Archiv fur mikrosk. Anat., Li, 1898. O. van der StrichT: "Nouvelles recherches sur la genese des globules rouges et des globules blancs du sang," Archives de Biolog., xn, 1892. O. van DER StrichT: "De la premiere origine du sang et des capillaires sanguins dans l'aire vasculaire du Lapin," Comples Rendus de la Soc. de Biolog. Paris, Ser. 10, 11, 1895. ZimmErmann : "Ueber die Kiemenarterienbogen des Menschen," Ver- handl. des Xtcn intermit, medic. Congresses, 11, 1891. 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. 39, 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 endo- derm. This cylinder is termed the archenteron and has connected with it the yolk-stalk and the allantois, the latter communicating with its somewhat dilated terminal portion, which also receives the ducts of the primitive kidneys and is known as the cloaca (Fig. 156). 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 appear- ance immediately in front of the anterior surface of the yolk-sac, and so the depression mentioned above becomes deepened (Fig. 155) to form the oral sinus. The floor of this, lined by ectoderm, is immediately opposite the ante- rior end of the archenteron, 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. 155, pm). In embryos of 2.15 mm. this membrane is still existent, but soon after it becomes per- 296 THE DIGESTIVE TRACT. 297 forated 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 noticeable in that the area over which the cloacal endoderm is in contact with the ectoderm to form the cloacal membrane (Fig. 156, cm) lies a little in front of the actual end of the archenteric cylin- der, the portion of the latter which lies poste- rior to the membrane forming what has been termed the post-anal gut . (p. an). This diminishes in size during develop- ment and early disap- pears altogether, and the pouch-like fold seen in Fig. 156 between the in- testinal portion of the archenteron and the al- lantoic stalk (al) deepen- ing until its floor conies 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 event- ually ruptures, so that the posterior communication of the archenteron with the exterior becomes established. This rupture, however, does not occur until a compara- 25 Fig. 155. — Reconstruction op the Anterior Portion of an Embryo of 2.15 MM. ab, Aortic bulb ; h, heart ; o, auditory capsule ; op, optic evagination ; pm, pharyngeal membrane. — (His.) 298 THE DEVELOPMENT OF THE HUMAN BODY. tively late period of development, until 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 lower end of the rectum, which bulges out, as it were, the regions immediately surrounding the membrane, pro- nc Fig. 156. — Reconstruction op the Hind End op an Embryo 6.5 mm. Long. al, Allantois; b, belly-stalk; cl, cloaca; cm, cloacal membrane; i, intes- tine; n, spinal cord; nc, notochord; p.an, post-anal gut; ur, out- growth to form ureter and metanephros; w, Wolffian duct. — (Keibel.) ducing a short ectodermal addition to the rectum, the end of which is the definitive anus. It will be noticed that the digestive tract thus formed consists of three distinct portions, an anterior, short, ecto- dermal portion, an endodermal portion representing the original archenteron, and a posterior short portion which is also ectodermal. The differentiation of the tract into THE MOUTH-CAVITY. 299 its various regions and the formation of the various organs found in relation with these may now be considered. The Development of the Mouth Region. — The deepening of the oral sinus by the development of the first branchial arch and its separation into the oral and nasal cavities by the development of the palate have already been de- scribed (p. 103), but, for the sake of continuity in descrip- tion, the latter process may be briefly recalled. At first the nasal pits communicate with the oral sinus by grooves lying one on each side of the fronto-nasal process, but by Fig. 157. — View of the Roof of the Oral Fossa of Embryo showing the Lip-groove and the Formation of the Palate. — (His.) the union of the latter with the maxillary processes this communication is partly interrupted, though the pits still retain connection with the oral sinus behind the maxillary process. At about the fifth week 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 deepening groove (Fig. 157), which separates an anterior fold, the lip, from the jaw proper (Fig. 158). From the premaxillary and maxillo-pala- 300 THE DEVELOPMENT OF THE HUMAN BODY. tine portions of the upper jaw, shelf -like ridges then begin to grow backward and inward, and at about the beginning of the third month these meet in the median line to form the palate, completing the separation of the definitive mouth from the nasal cavity. At the point of meeting of the premaxillary and maxillary shelves a small com- munication between the two cavities persists for a time, frequently until after birth; it allows passage of the ante- rior palatine vessels and nerves, and places the organ of Jacobson (p. 457) in communication with the mouth. Later the opening becomes closed over by mucous mem- brane, but it may be recognized in the dried skull as the foramen incisivum (anterior palatine canal) . Before the formation of the palate begins, a pouch is formed in the median line of the roof of the oral sinus, just in front of the pharyngeal membrane, by an upgrowth of the epithelium. This 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. 418). The Development of the Teeth. — When the epithelial downgrowth which gives rise to the lip groove is formed, a horizontal outgrowth develops from it which extends backward into the substance of the jaw, forming what is termed the dental shelf (Fig. 1 58, A). This at first is situ- ated on the anterior surface of the jaw, but with the con- tinued development of the lip fold it is gradually shifted until it comes to lie upon the free surface (Fig. 158, B), where its superficial edge is marked by a distinct groove, the dental groove (Fig. 157). At first the dental shelf of each jaw is a continuous plate of cells, uniform in thick- ness 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 THE TEETH. 30I surface of which the thickening moulds itself to form a cap, termed the enamel organ (Fig. 158, B). These ten papillae 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 obliquely into what, in the lower Fig. 158. — Transverse Sections through the Lower Jaw showing the Formation of the Dental Shelf in Embryos of (A) 17 mm. and (jB) 40 mm. — (Rose.) jaw, was originally its under surface (Fig. 158, B), so that the edge of the shelf is free to grow still deeper into the surface 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, ca- nines, and premolars of the permanent dentition. The 302 THE DEVELOPMENT OF THE HUMAN BODY. lateral edges of the dental shelf being continued outward toward the articulations of the jaws as prolongations which are not connected with the surface epithelium, op- portunity is afforded for the development of three addi- tional thickenings on each side in each jaw, and, papillae developing beneath these, twelve additional tooth-germs are formed. These represent the permanent molars; their formation 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 de- layed until about the fifth year. 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 epithe- lial cells. In the mean time 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 vari- ous malformations. With the disappearance of the last remains of the 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 derived 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, 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 surface of the papilla, at an early stage assume a cylindrical form and become arranged in a definite layer, the enamel membrane (Fig. 159, SEi), while the remaining Missing Page Missing Page THE TONGUE. 305 roots of these then undergo partial absorption, and so are 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 considerable variation, but the usual sequence is somewhat as follows : Primary Dentition. Median incisors 6th to 8th month. Lateral incisors 7th to 9th month. First molars, Beginning of 2d year. Canines, 1J years. Second molars 3 to 3 J years. The teeth of the lower jaw generally precede those of the upper. Permanent Dentition. First molars, 7th year. Middle incisors 8th year. Lateral incisors, 9th year. First premolars, 10th year. Second premolars, 1 1th year. Canines, 1 Second molars, \ 13th t0 14th y ears 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 they fail 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 branchial arches, a small rounded elevation which has been termed the tuberculum impar. In later stages 26 3o6 THE DEVELOPMENT OF THE HUMAN BODY. (Fig. 1 60, A) this becomes larger and reaches its greatest development in embryos of about 8 mm., after which it becomes less prominent and finally unrecognizable, but before this there has appeared on each side of the floor of the mouth a longitudinal groove, each of which at its anterior end bends medially toward its fellow. By these alveolo-lingual grooves an area is marked out in the floor of the mouth which gradually becomes more and more prom- B tig. iou. — pwuk ue uk Pharynx of Embryos of (A) 7 and (B) 10 MM. SHOWING THE DEVELOPMENT OF THE TONGUE. Ep, Epiglottis; Sp, precervical sinus; t l and t 2 , median and lateral portions of the tongue; / to IV, branchial arches. — (His.) inent and rounded upon its oral surface, and forms the anterior portion of the tongue (Fig. 160, B, t 1 ). This median elevation is bounded at the sides and almost to the median line in front by the alveolo-lingual grooves, and posteriorly it is separated from the anterior edge of the second branchial arch by a distinct V-shaped groove, at the apex of which is a deep circular depression, the foramen crncum (see p. 313). The posterior portion of the tongue arises as thickenings THE TONGUE. 307 of the ventral ends of the second branchial arches, and is consequently a V-shaped structure, into the angle of which the posterior part of the anterior portion of the tongue fits (Fig. 161). The two portions, anterior and posterior, eventually fuse together, but the groove which originally separated them remains more or less clearly distinguish- able, the circumvallate pa- pilla? (see p. 458) develop- ing immediately anterior 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 mem- brane derived from the floor of the mouth and pharynx. 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 extrinsic muscles, the hyoglossi, genio- hyoglossi, styloglossi, palatoglossi, and chondroglossi. The last two muscles are innervated by the vagus nerve, and the remaining extrinsic muscles receive fibers from the hypo- glossal, while the lingualis is supplied partly by the hypoglossal and partly, apparently, by the facial through the chorda tym- pani. That the facial should take part in the supply is what might be expected from the mode of development of the tongue, but the hypoglossal has been seen to correspond to certain pri- marily postcranial metameres (p. 192), and its relation to struc- tures 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 evolution of the tongue the ex- trinsic 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 Fig. 161. — The Floor of the Pharynx op an Embryo of about 20 MM. ep, Epiglottis ; fc, foramen caecum ; t l and t 2 , median and lateral por- tions of the tongue. — (His.) 3 o8 THE DEVELOPMENT OF THE HUMAN BODY. segments would explain the distribution of its sensory nerves. The anterior portion, from its position, would naturally be sup- plied by branches from the fifth and seventh nerves, while the posterior portion might be expected to be supplied by the Fig. 162. — Diagram of the Distribution of the Sensory Nerves op 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.) seventh. There seems, however, to have been a dislocation forward, if it may be so expressed, of the mucous membrane, the sensory distribution of the ninth nerve extending forward upon the posterior part of the anterior portion of the tongue, THE SALIVARY GLANDS. 309 while a considerable portion 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 information 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 CW X/l S/n Fig. 163. — An Oblique Section through the Mouth Cavity of an Embryo op about 16 to 17 mm. cm, Meckel's cartilage ; id, inferior dental nerve ; nl, lingual nerve ; P, parotid gland; SL, septum of the tongue; si, sublingual gland; sm, submaxil- lary gland; t, tooth; XII, hypoglossal nerve. — (His.) deepens and eventually becomes closed in to form a hol- low 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 em- bedded in the connective tissue of the cheek. This tube is readily recognizable as the parotid gland and Stenson's duct, and from the latter as it passes across the masseter muscle a pouch-like outgrowth is early formed which probably represents the socia parotides. The submaxillary gland and Wharton's duct appear in 3IO THE DEVELOPMENT OF THE HUMAN BODY. embryos of about 13 mm. as a longitudinal ridge-like thickening of the epithelium of the floor of the alveolo- lingual groove (see p. 306). This ridge gradually sepa- rates from behind forward from the floor of the groove and sinks into the subjacent connective tissue, retaining, how- ever, its connection with the epithelium at its anterior end, 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-like downgrowths of the epithe- lium, which later increase considerably in number as well as in size, and constitute a group of glands which are gen- erally 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. 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. The Development of the Pharynx. — The pharynx repre- sents the most anterior part of the archenteron, that por- tion in which the branchial arches develop, and in the THE PHARYNX. 3" 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 prsecervi- calis already described (p. 101). Between the various branchial arches, grooves occur, representing the endo- dermal portions of the grooves which separate the arches. During development the first of these becomes converted into the tympanic cavity of the ear and the Eustachian tube (see Chap. XV) ; the second disappears in its upper part, the lower persisting as the groove of Rosenmilller and the fossa in which the tonsil is situ- ated; while the remaining two disappear, leaving traces of their existence in detached portions of their epithelium which form what are termed the branchial epithelial bodies, among which are the thyreoid and thymus glands. In the floor of the pharynx behind the thickenings which produce the tongue there is to be found in early stages a pair of thickenings passing horizontally backward and unit- ing in front so that they resemble an inverted fj (Fig. 164, /). These ridges, which form what is termed the furcula (His), are concerned in the formation of parts of the larynx (see p. 355). In the part of the roof of the pharynx which comes to lie between the openings of the Eustachian tubes, a collection of lymphatic tissue takes place beneath the mucous membrane, forming the pharyngeal tonsil, and immediately behind this there is formed in the median line an upwardly projecting pouch, Fig. 164. — The Floor of the Pharynx of an Em- bryo op 2.15 MM. /, Furcula ; /, median portion of tongue. — (His.) 312 THE DEVELOPMENT OF THE HUMAN BODY. the pharyngeal bursa, first certainly noticeable in em- bryos 6.5 mm. in length. This bursa has very generally been regarded as the persistent remains of Rathke's pouch (p. 300), 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), though what its signifi- cance may be is still uncertain. The tonsils are formed from the epithelium of the lower part of the second branchial groove. At about the fourth month solid buds begin to grow from the epithelium into the subjacent mesenchyme, and depressions appear on the surface of this region. I^ater 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 mean time lymphocytes, concerning whose origin there is a difference of opinion, collect in the sub- jacent mesenchyme and eventually aggregate to form lymphatic follicles in close relation with the buds. Whether the lymphocytes wander out from the blood into the mesenchyme or are derived directly from the epithe- lial cells is the question at issue. The tonsil may grow to a size sufficient to fill up com- pletely the depression in which it forms, but not infre- quently a marked depression, the fossa supratonsillaris , exists above it and represents a portion of the original second branchial furrow. Another portion of the same furrow is represented by a more or less prominent de- pression situated posteriorly to the opening of the Eusta- chian tube on each side and known as the groove of Rosenmilller. 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 THE BRANCHIAL EPITHELIAL BODIES. 313 of the inner branchial furrows. Five pairs of these struc- tures are developed and, in addition, there is a single un- paired median body. This last makes its appearance in embryos of about 3 mm., and gives rise to the major por- tion of the thyreoid body. It is situated immediately be- hind the anterior portion 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 extrem- ity becomes bilobed, and after the embryo has reached a length of 6 mm. it becomes completely separated from the Fig. 165. — Reconstructions op the Branchial Epitheual Bodies op Embryos op (A) 14 mm. and (S) 26 mm. ao, Aorta; Ith, lateral thyreoid; ph, pharynx; pth 1 and pth 2 , parathy- reoids; th, thyreoid; thy, thymus; vc, vena cava superior. — (Tourneux and Verdun.) floor of the pharynx. The point of its original origin is, however, permanently marked by a circular depression, the foramen ccecum (Fig. 161, jc). Later the bilobed body migrates down the neck and becomes a solid transversely elongated mass (Fig. 165, th), into the substance of which trabecular of connective tissue extend, dividing it into a network of anastomosing cords which later divide trans- versely to form follicles. When the embryo has reached a length of 2.6 cm., a cylindrical outgrowth arises from the 3H THE DEVELOPMENT OF THE HUMAN BODY. anterior surface of the mass, usually a little to the left of the median line, and extends up the neck a varying dis- tance, forming, when it persists until adult life, the so- called pyramid of the thyreoid body. This account of the pyramid follows the statements made by recent workers on the question (Tourneux and Verdun); His has claimed that it is the remains of the stalk connecting the thyreoid with the floor of the pharynx, and which he terms the thyreo-glossal duct. In addition to this median structure, one of the pairs of the lateral evaginations also take part in the formation of the thyreoid body. These are the lateral thyreoids (Fig. 165, Ith), and they arise from the posterior wall of the fourth branchial furrow, in embryos of about 8 mm. Separating from the furrow, they migrate backward to fuse in embryos of about 1 6 mm. with the posterior surface of the lateral portions of the median thyreoid. They form, however, only a relatively small portion of the entire thyreoid (Fig. 166, thm IV). Two other pairs of bodies enter into intimate relations with the thyreoid, forming what have been termed the parathyreoid bodies (Fig. 165, pth 1 and pth 2 ). One of these pairs arises as a thickening of the anterior wall of the fourth branchial groove and the other comes from the corresponding wall of the third groove. The members of the former pair, after separating from their points of ori- gin, come to lie on the dorsal surface of the lateral portions of the thyreoid body (Fig. 1 66, pthm IV) in close proximity to the lateral thyreoids, while the latter, passing further backward, come to rest behind the lower border of the thyreoid (Fig. 166, pthm III). The cells of these bodies do not become divided into cords by the ingrowth of connec- tive tissue to the same extent as those of the thyreoids, nor do they become separated into follicles, so that the THE BRANCHIAL EPITHELIAL BODIES. 315 pthm IV thm 1 V pthm III bodies are readily distinguishable by their structure from the thyreoid. From the posterior wall of the third branchial groove a pair of evaginations develop, similar to those which produce the lateral thyreoids. These elongate great- ly, and growing down- ward ventrally to the thyreoid and separat- ing from their points of origin, come to lie below the thyreoids, forming the thymus gland (Fig. 165, thy). As development pro- ceeds they pass further backward and come eventually to rest upon the anterior surface of the peri- cardium. The cavity which they at first contain is early oblit- erated and the glands assume a lobed ap- pearance and become traversed by trabe- culae of connective tissue. Lymphocytes, derived, according to some recent observations, directly from the epithelium of the glands, make their appearance and gradually increase in number until the original epi- Fig. 166. — Thyreoid, Thymus and Epi- thelial Bodies of a New-born Child. pthm III and pthm IV , Parathyreoids; sd, thyreoid; thm III, thymus; thm IV, lateral thyreoid. — (Groschujf.) 316 THE DEVELOPMENT OF THE HUMAN BODY. thelial cells are represented only by a number of peculiar spherical structures, consisting of cells arranged in con- centric layers and known as Hassal's corpuscles. The glands persist until about the second year after birth, when they undergo a degeneration into a mass of fibrous and adipose tissue. Fig. 167. — Diagram showing the Origin of the Various Branchial Epithelial Bodies. Ith, Lateral thyreoids; pp, postbranchial bodies; pkt 1 and pht 2 , para- thyreoids; th, median thyreoid; thy, thymus; I to IV, branchial grooves. — (Kohn.) Finally, a pair of outgrowths arise from the floor of the pharynx just behind the fifth branchial arch, in the region where the fifth groove, if developed, would occur. These post-branchial bodies, as they have been called, usually undergo degeneration at an early stage and disappear completely, though occasionally they persist as cystic structures embedded in the substance of the thyreoid. THE (ESOPHAGUS. 317 The relation of these various structures to the branchial grooves is shown by the annexed diagram (Fig. 1 67) ; and from it, it will be seen that the bodies derived from the third and fourth grooves are serially equivalent. Comparative embry- ology makes this fact still more evident, since, in the lower ver- tebrates, each branchial groove contributes to the formation of the thymus gland. The terminology used above for the various bodies is that generally applied to the mammalian organs, but it would be better, for the sake of comparison with other verte- brates, to adapt the nomenclature proposed by Groschuff, who terms each lateral thyreoid a thymus IV, while each thymus lobe is a thymus III. Similarly the parathyreoids are termed para- thymus III and IV, the term thyreoid being limited to the median thyreoid. The Musculature of the Pharynx. — The pharynx differs from other portions of the archenteron in the fact that its walls are furnished with voluntary muscles, the principal of which are the constrictors and the stylo-pharyngeus. This peculiarity arises from the relations of the pharynx to the branchial arches. It has been seen that in the higher mammalia the dorsal ends of the third, fourth, and fifth branchial cartilages disappear ; the muscles originally associated with these structures persist, however, and give rise to the muscles of the pharynx, which consequently are innervated by the ninth and tenth nerves. The Development of the (Esophagus. — From the ventral side of the lower portion of the pharynx an evagination develops at an early stage which is destined to give rise to the organs of respiration; the development of this may, however, be conveniently postponed to a later chapter (Chap. XII). The oesophagus is at first a very short portion of the archenteron (Fig. 168, A), but as the heart and diaphragm recede into the thorax it elongates (Fig. 168, B) until it eventually forms a considerable portion of the digestive tract. Its endodermal lining, like that of the rest of the 3i8 THE DEVELOPMENT OF THE HUMAN BODY. digestive tract except the pharynx, is surrounded by splanchnic mesoderm whose cells become converted into non-striated muscular tissue, which by the fourth month has separated into an inner circular and an outer longitudi- nal layer. Rj, Fig. 168. — Reconstructions of the Digestive Tract of Embryos of (a) 4.2 mm. and (b) 5 mm. all, Allantois; cl, cloaca; /, lung; li, liver; Rp, Rathke's pouch; S, stomach; /, tongue; th, thyreoid body; Wd, Wolffian duct; y, yolk-stalk. — (His.) The Development of the Stomach and Intestines. — By the time the embryo has reached a length of about 3 mm. its constriction from the yolk-sac has proceeded so far that a portion of the digestive tract anterior to the yolk-sac can be recognized as the stomach and a portion posterior as the intestine. At first the stomach is a simple spindle- THE STOMACH. 319 shaped enlargement (Fig. 168) and the intestine a tube without any coils or bends, but since in later stages the intestine grows much more rapidly in length than the ab- dominal cavity, a coiling of the intestine becomes neces- sary. The elongation of the stomach early produces changes in its position, its lower end bending over toward the right, while its upper end, owing to the development of the liver, is forced somewhat toward the left. At the same time the entire organ undergoes a rotation about its longitudinal axis through nearly 90 degrees, so that, as the result of the combination of these two changes, what was originally its ventral border becomes its lesser curvature and what was originally its left surface becomes its ventral surface. Hence it is that the left pneumogastric nerve passes over the ventral and the right over the dorsal surface of the stomach in the adult. In the mean time the elongation of the oesophagus has carried the stomach further away from the lower end of the pharynx, and from being spindle-shaped it has become more pyriform, as in the adult. The growth of the intestine results in its being thrown into a loop opposite the point where the yolk-stalk is still connected with it, the loop projecting ventrally into the portion of the ccelomic cavity which is contained within the umbilical cord, and being placed so that its upper limb lies to the right of the lower one. Upon the latter a slight pouch-like lateral outgrowth appears which is the begin- ning of the cacum and marks the line of union of the fu- ture small and large intestine. The small intestine, con- tinuing to lengthen more rapidly than the large, assumes a sinuous course (Fig. 169) in which it is possible to recog- nize six primary coils which may be recognized until ad- 320 THE DEVELOPMENT OF THE HUMAN BODY. vanced stages of development and even in the adult (Mall). The first of these is at first indistinguishable from the pyloric portion of the stomach and can be recog- nized as the duodenum only by the fact that it has con- nected with it the ducts of the liver and pancreas; as de- velopment proceeds, however, its caliber diminishes and it assumes the appearance of a portion of the intestine. Fig. 169. — Reconstruction ok Embryo of 20 mm. Caecum; K, kidney; L, liver; S, stomach; SC, suprarenal bodies; II 7 , mesonephros. — (Mall.) The remaining coils elongate rapidly and are thrown into numerous secondary coils, all of which are still con- tained within the ccelom of the umbilical cord (Fig. 170). When the embryo has reached a length of about 40 mm. the coils rather suddenly return to the abdominal cavity, THE INTESTINE. 321 and now the caecum is thrown over toward the right, so that it comes to lie immediately beneath the liver on the right side of the abdominal cavity, a position which it re- tains until about the fourth month after birth (Treves). The portion of the large intestine which formerly pro- jected into the umbilical ccelom now lies transversely across the upper part of the abdomen, crossing in front of the duodenum and having the remaining portion of the small intestine below it. The elongation continuing, the Fig. 170. — Reconstruction of the Intestine of an Embryo of 19 mm. The Figures on the Intestine Indicate the Primary Coils. — (Mall.) secondary coils of the small intestine become more numer- ous and the lower portion of the large intestine is thrown into a loop which extends transversely across the lower part of the abdominal cavity and represents the sigmoid flexure of the colon. At the time of birth this portion of the large intestine is relatively much longer than in the adult, amounting to nearly half the entire length of the colon (Treves), but after the fourth month after birth a readjustment of the relative lengths of the parts of the 27 322 THE DEVELOPMENT OF THE HUMAN BODY. colon occurs, the sigmoid flexure becoming shorter and the rest of the colon proportionally longer, whereby the caecum is pushed downward until it lies in the right iliac fossa, the ascending colon being thus established. Fig. 171. — Representation of the Coilings op the Intestine in the Adult Condition. The Numbers indicate the Primary Coils. — (Mall.) When this condition has been reached, the duodenum, after passing downward for a short distance so as to pass dorsally to the transverse colon, bends toward the left and the secondary coils derived from the second and third THE INTESTINE. 323 primary coils come to occupy the left upper portion of the abdominal cavity. Those from the fourth primary coil pass across the middle line and occupy the right upper part of the abdomen, those from the fifth cross back again to the left lumbar and iliac regions, and those of the sixth take possession of the false pelvis and the right iliac region (Fig. 171). Slight variations from this arrangement are not infrequent, but it occurs with sufficient frequency to be regarded as the normal. A failure in the readjustment of the relative lengths of the different parts of the colon may also occasionally occur, in which case the caecum will retain its embryonic position beneath the liver. The yolk-stalk is continuous with the intestine at the extremity of the loop which extends out into the umbilical coelom, and when the primary coils become apparent its point of attach- ment lies in the region of the sixth coil. As a rule, the caliber of the stalk does not increase proportionally with that of the intestine and even- tually its embryonic portion disap- pears completely. Occasionally, how- ever, this portion of it does partake of the increase in size which occurs in ,. Fig. 172. — Cecum of the intestine, and it forms a blind Embryo op 10.2 cm. pouch of varying length, known as c, Colon; i, ileum. Meckel's diverticulum (see p. 135). The ccecum has been seen to arise as a lateral outgrowth at a time when the intestine is first drawn out into the umbilicus. During subsequent development it continues to increase in size, until it forms a conical pouch arising from the colon just where it is joined by the small intestine. The enlargement of its terminal portion does not keep. 324 THE DEVELOPMENT OF THE HUMAN BODY. pace, however, with that of the portion nearest the intes- tine, but it becomes gradually more and more distin- guished and gives rise to the vermiform appendix. At birth the original conical form of the entire outgrowth is still distinguishable, though it is more properly de- scribed as funnel-shaped, but later the proximal part, con- tinuing to increase in diameter at the same rate as the colon, becomes sharply separated from the appendix, forming the caecum of adult anatomy. Fig. 173. — Reconstruction of a Portion op the Intestine of an Embryo of 28 mm., showing the Longitudinal Folds from which the Villi are Formed. — (Berry.) Up to the time when the embryo has reached a length of 14 mm., the inner surface of the intestine is quite smooth, but when a length of 19 mm. has been reached, the mu- cous membrane of the upper portion becomes thrown into longitudinal folds, and later these make their appearance throughout its entire length (Fig. 173). Later, in em- bryos of 60 mm., these folds break up into numbers of conical processes, the villi, which increase in number THE LIVER. 325 with the development of the intestine, the new villi ap- pearing in the intervals between those already present. A remarkable phenomenon has recently been described as occurring in the duodenum of embryos of about 12.5 mm. It consists in a rapid growth in the thickness of the mucous mem- brane, whereby the lumen of the intestine immediately below the opening of the hepatic and pancreatic ducts becomes greatly reduced in size and is finally completely obliterated. This condition persists until the embryo has reached a length of 14.5 mm., when the lumen again appears (Tandler). This process is interesting in connection with the occasional occurrence in new-born children of an atresia of the duodenum. The Development of the Liver. — The liver makes its appearance in embryos of about 3 mm. as a longitudinal groove upon the ventral surface of the archenteron just below the stomach and between it and the umbilicus. The endodermal cells lining the anterior portion of the groove early undergo a rapid proliferation, and form a solid mass which projects ventrally into the substance of a horizontal shelf, the septum transversum (see p. 336), attached to the ventral wall of the body. This solid mass (Fig. 1 74, L) forms the beginning of the liver proper, while the lower portion of the groove, which remains hollow, represents the future gall-bladder (Fig. 174, B). Con- strictions appearing between the intestine and both the hepatic and cystic portions of the organ gradually separate these from the intestine, until they are united to it only by a stalk which represents the ductus communis choledo- chus (Fig. 174). The further development of the liver, so far as its exter- nal form is concerned, consists in the rapid enlargement of the hepatic portion until it occupies the greater part of the upper half of the abdominal cavity, its ventral edge ex- tending as far down as the umbilicus. In the rabbit its substance becomes divided into four lobes corresponding 326 THE DEVELOPMENT OF THE HUMAN BODY. to the four veins, umbilical and omphalo-mesenteric, which traverse it, and the same condition occurs in the human embryo, although the lobes are not so clearly indi- cated upon the surface as in the rabbit. The two om- phalo-mesenteric lobes are in close apposition and may almost be regarded as one, a median ventral lobe which embraces the ductus venosus (Fig, 174, B, DV), while the umbilical lobes are more lateral and dorsal and repre- Fig. 174. — Reconstructions op the Liver Outgrowths of Rabbit Embryos of (A) 5 mm. and (B) of 8 mm. B, Gall-bladder; d, duodenum; DV, ductus venosus; L, liver; pm, ventral pancreas; rL, right lobe of the liver; S, stomach. — (Hammar.) sent the right (rL) and left lobes of the adult liver. The remaining definitive lobes, the spigelian, quadrate and caudate, are of later formation, the first two standing in relation to the vessels which cross the lower surface of the liver, while the caudate is formed by a portion of the right lobe which arches across the upper part of the ductus venosus. The ductus communis choledochus is at first wide and THE LIVER. 327 short, and near its proximal end gives rise to a small out- growth on each side, one of which becomes the ventral pancreas (Fig. 178, B, pm). Later it elongates and be- comes more slender, and the gall-bladder is constricted off from it, the connecting stalk becoming the cystic duct. The hepatic ducts are apparently developed from the liver substance and are relatively late in appearing. Shortly after the hepatic portion has been differen- tiated its substance becomes permeated by numerous Fig. 175. — Transverse Section through the Liver of an Embryo ok Four Months. in, Intestine; /, liver; W, Wolffian body. — (Toldt and Zuckerkandl.) blood-vessels, and so divided into numerous anastomosing trabecular (Fig. 175). These are at first irregular in size and shape, but later they become more slender and more regularly cylindrical, forming what have been termed the hepatic cylinders. In the center of each cylinder, where the cells which form it meet together, a fine canal appears, the beginning of a bile capillary, the cylinders thus be- coming converted into tubes with fine lumina. This oc- 328 THE DEVELOPMENT OF THE HUMAN BODY. curs at about the fourth week of development and at this time a cross-section of a cylinder shows it to be composed of about three or four hepatic cells (Fig. 176, A), among which are to be seen groups of smaller cells (e) which are erythrocytes, the liver having assumed by this time its haematopoietic function (see p. 244). This condition of affairs persists until birth, but later the cylinders undergo an elongation, the cells of which they are composed slip- Fig. 176. — Transverse Sections of Portions op the Liver op (A) a Fetus of Six Months and (B) a Child op Four Years. be, Bile capillary; e, erythrocyte; he, hepatic cylinder. — (Toldt and Zuckerkandl.) ping over one another apparently, so that the cylinders become thinner as well as longer and show for the most part only two cells in a transverse section (Fig. 176, B); and in still later periods the two cells, instead of lying opposite one another, may alternate, so that the cylinders become even more slender. The bile capillaries seem to make their appearance first in cylinders which lie in close relation to branches of the THE LIVER. 329 portal vein (Fig. 177) and thence extend throughout the neighboring cylinders, anastomosing with capillaries de- veloping in relation to neighboring portal branches. As the extension so proceeds the older capillaries continue to enlarge and later become transformed into bile-ducts (Fig. 1 77, C), the cells of the cylinders in which these capillaries were situated becoming converted into the epithelial lining of the ducts. The lobules, which form so characteristic a feature of the adult liver, are late in appearing, not being fully de- FlG. 177. — Injected Bile Capillaries of Pig Embryos of (A) 8 cm., (S) 16 cm., and (C) of Adult Pig. — (Hendrickson.) veloped until some time after birth. They depend upon the relative arrangement of the branches of the portal and hepatic veins; these at first occupy distinct territories of the liver substance, being separated from one another by practically the entire thickness of the liver, although of course connected by the capillaries which lie between the hepatic cylinders. During development the two sets of branches extend more deeply into the liver substance, each invading the territory of the other, but they can readily be distinguished from one another by the fact that the portal branches are enclosed within a sheath of con- 330 THE DEVELOPMENT OF THE HUMAN BODY. nective tissue (Glisson's capsule) which is lacking to the hepatic vessels. At about the time of birth the branches of the hepatic veins give off at intervals bunches of terminal vessels, around which branches of the portal vein arrange themselves, the liver tissue becoming divided up into a number of areas which may be termed hepatic islands, each of which is surrounded by a number of portal branches and contains numerous dichotomously branch- ing hepatic terminals. Later the portal branches sink into the substance of the islands, which thus become lobed, and finally the sinking in extends so far that the original island becomes separated into a number of smaller areas or lobules, each containing, as a rule, a single hepatic terminal (the intralobular vein) and being surrounded by a number of portal terminals (interlobular veins), the two systems being united by the capillaries which separate the cylinders contained within the area. The lobules are at first very small, but later they increase in size by the ex- tension of the hepatic cylinders. Frequently in the human liver lobules are to be found con- taining two intralobular veins, a condition which results from an imperfect subdivision of a lobe of the original hepatic island. The liver early assumes a relatively large size, its weight at one time being equal to that of the rest of the body, and though in later embryonic stages its relative size dimin- ishes, yet at birth it is still a voluminous organ, occupying the greater portion of the upper half of the abdominal cavity and extending far over into the left hypochon- drium. Just after birth there is, however, a cessation of growth, and the subsequent increase proceeds at a much slower rate than that of the rest of the body, so that its rela- tive size becomes still more diminished (see Chap. XVI). The cessation of growth affects principally the left lobe THE PANCREAS. 33' DC ft and depends upon an actual degeneration of portions of the liver tissue, the cells disappearing completely, while the ducts and blood-vessels originally present persist, the former constituting the vasa aberranlia of adult anatomy. These are usually espe- cially noticeable at the left edge of the liver, be- tween the folds of the left lateral ligament, but they may also be found along the line of the vena cava, around the gall- bladder, and in the re- gion of the left longitudi- nal fissure. The Development of the Pancreas. — The pan- creas arises a little later than the liver, as three separate outgrowths, one from the dorsal surface of the duodenum (Fig. 178, DP) almost opposite the liver outgrowth, and one on each side from the lower part of the com- mon bile-duct. Of the latter outgrowths, that upon the left side (Vps) early begins to degener- ate and completely disappears, while that of the right side (Vpd) continues its development to form what has been termed the ventral pancreas. Both this and the dorsal pancreas continue to elongate, the latter lying to Fig. 178. — Reconstruction op the Pancreatic Outgrowths op an Embryo of 7.5 mm. D, Duodenum; Dc, ductus communis choledochus; DP, dorsal pancreas; Vpd and Vps, right and left ven- tral pancreas. — (Hetty.) 332 THE DEVELOPMENT OF THE HUMAN BODY. the left of the portal vein, while the former, at first situ- ated to the right of the vein, later grows across its ventral surface so as to come into contact with the dorsal gland, with which it fuses so intimately that no separation line can be distinguished. The body and tail of the adult pancreas represent the original dorsal outgrowth, while the right ventral pancreas becomes the head. Both the dorsal and ventral outgrowths early become lobed, and the lobes becoming secondarily lobed and this lobation repeating itself several times, the compound tubular structure of the adult gland is acquired, the very numerous terminal lobules becoming the secreting acini, while the remaining portions become the ducts. Of the principal ducts, there are at first two; that of the dorsal pancreas, the duct of Santorini, opens into the duodenum on its dorsal surface, while that of the ventral outgrowth, the duct of Wirsung, opens into the ductus communis chol- edochus. When the fusion of the two portions of the gland occurs, an anastomosis of branches of the two ducts develops and the terminal portion of the duct of Santorini usually degenerates, so that the secretion of the entire gland empties into the common bile-duct through the duct of Wirsung. In the connective tissue which separates the lobules of the gland groups of cells, arranged so as to form anasto- mosing trabecular, occur. These appear to have no con- nection with the ducts of the gland, and form what are termed the areas of Langerhans. They seem to arise by the separation off of portions of the acini, but what their later history and function may be is as yet uncertain. LITERATURE. J. M. Berry : "On the Development of the Villi of the Human Intestine," Anat. Anzeiger, xvi, 1900. LITERATURE. 333 J Brachet: "Recherches sur le developpement du pancreas et du foie," Journ. de I'Anat. et de la Physiol., xxxn, 1896. J. H. ChieviTz: "Beitrage zur Entwicklungsgeschichte der Speichel- driisen," Archiv fur Anat. und Physiol., Anat. Abth., 1885. K. Groschuff: "Ueber das Vorkommen eines Thymussegmentes der vierten Kiementasche beim Menschen," Anat. Anzeiger, xvn, 1900. J. A. Hammar: "Einige Plattenmodelle zur Beleuchtung der fruheren em- bryonal Leberentwicklung," A rchiv fur A nat und Physiol., Anat. Abth., 1893. J. A. Hammar: "Notiz fiber die Entwickelung der Zunge undderMund- speicheldriisen beim Menschen," Anat. Anzeiger, xix, 1901. K. Helly: "Zur Entwickelungsgeschichte der Pancreasanlagen und Duodenalpapillen des Menschen," Archiv fur mikrosk. Anat., lvi, 1900. W. F. Hendrickson: "The Development of the Bile-capillaries as re- vealed by Golgi's Method," Johns Hopkins Hospital Bulletin, 1898. W. His: "Anatomiemenschlicher Embryonen," Leipzig, 1882-1886. F. KeibEL: " Zur Entwickelungsgeschichte des menschlichen Urogenital- apparatus," Archiv fiir Anat. und Physiol., Anat. Abth., 1896. G. Killian: "Ueber die Bursa und Tonsilla pharyngea," Morphol. Jahr- buch, xiv, 1888. A. Kohn: "Die Epithelkorperchen," Ergebnisse der Anat. und Entwick- lungsgesch., ix, 1899. F. P. Mall: "Ueber die Entwickelung des menschlichen Darmes und seiner Lage beim Erwachsenen," Archiv fur Anat. und Physiol. Anat.t Abth. Supplement, 1897. J. F. Meckel: " Bildungsgeschichte des Darmkanals der Saugethiere und namentlich des Menschen," Archiv fur Anat. und Physiol., in, 1817. C. R8sE: "Ueber die Entwicklung der Zahne des Menschen," Archiv fiir mikrosk. Anat., xxxvin, 1891. A. Swaen: " Recherches sur le developpement du foie, du tube digestif, de Tamere-cavite' du peritoine et du m^sentere," Journ. de I'Anat. et de la Physiol., xxxn, 1896, and xxxin, 1897. J. TandlER: "Zur Entwicklungsgeschichte des menschlichen Duodenum infruhen Embryonalstadien," Morphol. Jahrbuch, xxix, 1900. C. ToldT and E. ZuckERKANDL: "Ueber die Form und Texturveran- derungen der menschlichen Leber wahrend des Wachsthums," Sitz- ungsber. der kais. Akad. Wissensch. Wien., Math.-N aturwiss . Classe, Lxxn, 1875. F. Tourneux and P. Verdun: "Sur les premiers d£veloppements de la Thyroide, du Thymus et des glandes parathyroidiennes chez l'homme," Journ. de I'Anat. et de la Physiol., xxxin, 1897. F. Treves : ' ' Lectures on the Anatomy of the Intestinal Canal and Peri- toneum in Man," British Medical Journal, I, 1885. CHAPTER XL THE DEVELOPMENT OF THE PERICARDIUM AND PLEURO-PERITONEUM, THE DIA- PHRAGM AND THE SPLEEN. It has been seen (p. 248) that the heart makes its ap- pearance at a stage when the greater portion of the ven- tral surface to the intestine is still open to the yolk-sac. The ventral mesoderm splits to form the somatic and splanchnic layers and the heart develops as a fold in the latter on each side of the median line, projecting into the ccelomic cavity enclosed by the two layers (Fig. 126, A). As the constriction of the anterior part of the embryo proceeds, the two heart folds are brought nearer together and later meet, so that the heart becomes a cylindrical structure lying in the median line of the body and is sus- pended in the coelom by a ventral band, the ventral meso- cardium, composed of two layers of splanchnic mesoderm which extend to it from the ventral wall of the body, and by a similar band, the dorsal mesocardium, which unites it with the splanchnic mesoderm surrounding the diges- tive tract. The ventral mesocardium soon disappears (Fig. 126, C) and the dorsal one also vanishes somewhat later, so that the heart comes to lie freely in the ccelomic cavity, except for the connections which it makes with the body-walls by the vessels which enter and arise from it. The ccelomic cavity of the embryo does not at first com- municate with the extra-embryonic coelom, which is formed at a very early period (see p. 84), but later when 334 THE PERICARDIUM. 33 5 the splitting of the embryonic mesoderm takes place the two cavities become continuous behind the heart but not anteriorly, since the ventral wall of the body is formed in the heart region before the union can take place It is possible, therefore, to recognize two por- tions in the embryonic coelom, an anterior one, the parietal cavity (His), which is never connected laterally with the extra-embry- onic cavity, and a posterior one, the trunk cavity, which is so con- nected. The heart is situated in the parietal cavity, a consider- able portion of which is destined to become the pericardial cavity. Since the parietal cavity lies immediately anterior to the still wide yolk-stalk, as may be seen from the position of the heart in the embryo shown in Fig. 42, it is bounded posteriorly by the yolk-stalk. This boundary is complete, however, only in the median line, the cavity being continuous on either side of the yolk-stalk with the trunk-cavity by passages which have been termed the recessus parietales (Fig. 179, Bp and Rca). Pass- ing forward toward the heart in the splanchnic mesoderm which surrounds the yolk-stalk are the large omphalo-mesenteric veins, one on either side, and these shortly become so large as to bring the Rca Fig. 179. — Reconstruction of a Rabbit Embryo of Eight Days, with the Pericardial Cavity Laid Open. A, Auricle; Aob, aortic bulb; A. V., auriculo-ventricular communication; Bp, ven- tral parietal recess; Om, omphalo - mesenteric vein ; Pc, pericardial cavity; Rca, dorsal parietal recess ; sv, sinus venosus; V, ventricle. —{His.) 336 THE DEVELOPMENT OF THE HUMAN BODY. splanchnic mesoderm in which they lie in contact with the somatic mesoderm which forms the lateral wall of each recess. Fusion of the two layers of mesoderm along the course of the veins now takes place, and each recess thus becomes divided into two parallel pas- sages, which have been termed the dorsal (Fig. 180, rpd) and ventral (rpv) parietal recesses. Later the two veins fuse in the upper portion of their course to form the begin- ning of the sinus venosus, with the result that the ventral recesses become closed below and their continuity with the Fig. 180. — Transverse Sections of a Rabbit Embryo showing the Division of the Parietal Recesses by the Omphalo-mesenteric Veins. am, Amnion; rp, parietal recess; rpd and rpv, dorsal and ventral divisions of the parietal recess; vom, omphalo-mesenteric vein. — (Ravn.) trunk-cavity is interrupted, so that they form two blind pouches extending downward a short distance from the ventral portion of the floor of the parietal cavity. The dorsal recesses, however, retain their continuity with the trunk-cavity until a much later period. By the fusion of the omphalo-mesenteric veins men- tioned above, there is formed a thick semilunar fold which projects horizontally into the coelom from the ventral wall of the body and forms the floor of the ventral part of the parietal recess. This is known as the septum iransver- THE PERICARDIUM. 337 sum, and besides containing the anterior portions of the omphalo-mesenteric veins, it also furnishes a passage by which the ductus Cuvieri, formed by the union of the jugular and cardinal veins, reaches the heart. Its dorsal edge is continuous in the median line with the mesoderm surrounding the digestive tract just opposite the region Fig. 181. — Reconstruction from a Rabbit Embryo of Nine Days showing the Septum Transversum from Above. am, Amnion; at, auricle; dc, ductus Cuvieri; rpd, dorsal parietal recess. — (Raim.) where the liver outgrowth will form, but laterally this edge is free and forms the ventral walls of the dorsal parie- tal recess. An idea of the relations of the septum at this stage may be obtained from Fig. 181, which represents the anterior surface of the septum, together with the related parts, in a rabbit embryo of nine days. 338 THE DEVELOPMENT OF THE HUMAN BODY. The Separation of the Pericardial Cavity. — The septum transversum is at first almost horizontal, but later it be- comes decidedly oblique in position, a change associated with the backward movement of the heart. As the clo- sure of the ventral wall of the body extends posteriorly the ventral edge of the septum gradually slips downward upon it, while the dorsal edge is held in its former position by its attachment to the wall of the digestive tract and the ductus Cuvieri. The anterior surface of the septum thus comes to look ventrally as well as forward and the parietal cavity, having taken up into itself the blind pouches which represented the ventral recesses, comes to lie to a large extent ventral to the posterior recesses. As may be seen from Fig. 181, the ductus Cuvieri, as they bend from the lateral walls of the body into the free edges of the septum, form a marked projection which diminishes considerably the opening of the dorsal recesses into the parietal cavity. In later stages this projection increases and from its dorsal edge a fold, which may be regarded as a continuation of the free edge of the septum, projects into the upper portions of the recesses and eventually fuses with the median portion of the septum attached to the wall of the gut. In this way the parietal cavity be- comes a completely closed sac, and is henceforward known as the pericardial cavity, the original coelom being now divided into two portions, (i) the pericardial and (2) the pleuro- peritoneal cavities, the latter consisting of the ab- dominal ccelom together with the two dorsal parietal recesses which have been separated from the pericardial (parietal) cavity and are destined to be converted into the pleural cavities. The Formation of the Diaphragm. — It is to be remem- bered that the attachment of the transverse septum to the ventral wall of the digestive tract is opposite the point THE DIAPHRAGM. 339 where the liver outgrowth develops. When, therefore, the outgrowth appears, it pushes its way into the sub- stance of the septum, which thus acquires a very con- siderable thickness, especially toward its dorsal edge, and it furthermore becomes differentiated into two layers, an upper one, which forms the floor of the ventral portion of the pericardial cavity and encloses the Cuvierian ducts, and a lower one which contains the liver. The upper layer is comparatively thin, while the lower forms the greater Fig. 182. — Diagrams of (A) a Sagittal Section op an Embryo showing the Liver Enclosed within the Septum Transversum; (£>) a Frontal Section of the Same; (C) a Frontal Section of a Later Stage when the Liver has Separated from the Diaphragm. All, Allantois; CI, cloaca; D, diaphragm; Li, liver; Ls, suspensory ligament of the liver ; M, mesentery ; A/g, mesogastrium ; Pc, pericardium ; S, stomach; ST, septum transversum; U, umbilicus. part of the thickness of the septum, its posterior surface meeting the ventral wall of the abdomen at the level of the anterior margin of the umbilicus (Fig. 182, A). In later stages of development the layer containing the liver becomes separated from the upper layer by two grooves which, appearing at the sides and ventrally imme- diately above the liver (Fig. 182, B), gradually deepen toward the median line and dorsally. These grooves do 34° THE DEVELOPMENT OF THE HUMAN BODY. not, however, quite reach the median line, a portion of the lower layer of the septum being left in this region as a fold, situated in the sagittal plane of the body and attached above to the posterior surface of the upper layer and be- low to the anterior surface of the liver, beyond which it is continued down the ventral wall of the abdomen to the umbilicus (Fig. 182, C, Ls). This is the suspensory liga- ment of the liver of adult anatomy, and in the free edge of its prolongation down the ventral wall of the abdomen the umbilical vein passes to the under surface of the liver, while the free edge of that portion which lies between the liver and the digestive tract contains the omphalo-mesen- teric (portal) vein, the common bile-duct, and the hepatic artery. The diagram given in Fig. 182 will, it is hoped, make clear the mode of formation and the relation of this fold, which, in its entirety, constitutes what is sometimes termed the ventral mesentery. And riot only do the grooves fail to unite in the median line, but they also fail to completely separate the liver from the upper layer of the septum dorsally, the portion of the lower layer which persists in this region forming the coronary ligament of the liver. The portion of the lower layer which forms the roof of the grooves becomes the layer of peritoneum covering the posterior surface of the upper layer (which represents the diaphragm), while the portion which remains connected with the liver con- stitutes its peritoneal investment. In the mean time changes have been taking place in the upper layer. As the rotation of the heart occurs, so that its auricular'portion comes to lie anterior to the ventricle, the Cuvierian ducts are drawn away from the septum and penetrate the posterior wall of the pericardium, the sepa- ration being assisted by the continued descent of the at- tachment of the edge of the septum to the ventral wall of THE DIAPHRAGM. 34 1 the body. During this descent, when the upper layer of the septum has reached the level of the fourth cervical seg- ment, a portion of the myotome of that segment becomes prolonged into it and the layer assumes the characteristics of the diaphragm, the supply of whose musculature from the fourth cervical nerve through the phrenic is thus ex- plained. The diaphragm is as yet, however, incomplete dorsally, where the dorsal parietal recesses are still in continuity with the trunk-cavity. With the increase in thickness of the septum transversum, these recesses have acquired a considerable length antero-posteriorly, and into their upper portions the outgrowths from the lower part of the pharynx which form the lungs (see page 353) begin to pro- ject. The recesses thus become transformed into the pleural cavities, and as the diaphragm continues to de- scend, slipping down the ventral wall of the body, and drawing with it the pericardial cavity, the latter comes to lie entirely ventral to the pleural cavities. The free borders of the diaphragm, which now form the ventral boundaries of the openings by which the pleural and peri- toneal cavities communicate, begin to approach the dorsal wall of the body, with which they finally unite, and so complete the separation of the cavities. The pleural cav- ities continue to enlarge after their separation and, ex- tending laterally, pass between the pericardium and the lateral walls of the body until they finally almost com- pletely surround the pericardium. The intervals between the two pleura form what are termed the mediastina in adult anatomy, the posterior (dorsal) mediastinum, in which the oesophagus lies, being the remains of the median portion of the septum transversum which was attached to the wall of the gut. The downward movement of the septum tran$versum 342 THE DEVELOPMENT OF THE HUMAN BODY. extends through a very considerable interval, which may- be appreciated from the diagram shown in Fig. 183. From this it may be seen that in early embryos the septum is situated just in front of the first cervical segment and that it lies very obliquely, its free edge being decidedly posterior to its ventral attach- ment. When the downward displacement occurs, the ven- tral edge at first moves more rapidly than the dorsal, and soon comes to lie at a much lower level. The backward movement continues through- out the entire length of the cervical and thoracic regions, and when the level of the tenth thoracic segment is reached the separation of the pleural and peritoneal cavi- ties is completed and then the dorsal edge begins to de- scend more rapidly than the ventral, so that the dia- phragm again becomes ob- lique in the same sense as in the beginning, a position which it retains in the adult. The Development 0} the Peritoneum. — The peritoneal cavity is developed from the trunk-cavity of early stages and is at first in free communication on all sides of the yolk-stalk with the extra-embryonic coelom. As the ven- tral wall of the body develops the two cavities become more and more separated, and with the formation of the umbilical cord the separation is complete. Along the Fig. 183. — Diagram showing the Position op the Dia- phragm in Embryos of Dif- ferent Ages. — {.Mall.) THE PERITONEUM. 343 mid-dorsal line of the body the archenteron forms a pro- jection into the cavity and later moves further out from the body-wall into the cavity, pushing in front of it the peritoneum, which thus comes to surround the intestine, forming its serous coat, and from it is continued back to the dorsal body- wall forming the mesentery. It has already been seen that on the separation of the liver from the septum transversum, the tissue of the latter gives rise to the peritoneal covering of the liver and of the posterior surface of the diaphragm, and also to the ventral mesentery. When the separation is taking place, the rotation of the stomach already described (p. 319) occurs, with the result that the portion of the ventral mesentery which stretches between the lesser curvature of the stom- ach and the liver shares in the rotation and comes to lie in a plane practically at right angles with that of the sus- pensory ligament, its surfaces looking dorsally. and ven- trally and its free edge being directed toward the right. This portion of the ventral mesentery forms what is termed the lesser omentum, and between it and the dorsal surface of the stomach as the ventral boundaries and the dorsal wall of the abdominal cavity dorsally there is a cavity, whose floor is formed by the dorsal mesentery of the stomach, the mesogastrium, the roof by the under surface of the left half of the liver, while to the right it communicates with the general peritoneal cavity dorsal to the free edge of the lesser omentum. This cavity is known as the lesser sac of the peritoneum, and the opening into it from the general cavity or greater sac is termed the foramen of Winslow. Later, the floor of the lesser sac is drawn downward to form a broad sheet of peri- toneum lying ventral to the coils of the small intestine and consisting of four layers; this represents the great omentum of adult anatomy (Fig. 187). 344 THE DEVELOPMENT OF THE HUMAN BODY. Below the level of the upper part of the duodenum the ventral mesentery is wanting ; only the dorsal mesentery occurs. So long as the intestine is a straight tube the length of the intestinal edge of this mesentery is practic- ally equal to that of its dorsal attached edge. The intes- tine, however, increasing in length much more rapidly than the abdominal walls, the intestinal edge of the mes- entery soon becomes very much longer than the attached edge, and when the intestine grows out into the umbilical ccelom the mesentery accompanies it (Fig. 184). As the coils of the intes- tine develop, the intestinal edge of the mesentery is thrown into corresponding folds, and on the return of the intestine to the ab- dominal cavity the mesentery is thrown into a somewhat funnel- like form by the twisting of the intestine to form its primary loop (Fig. 185). All that portion of the mesentery which is attached to the part of the intestine which will later become the jejunum, ileum, ascending and transverse colon, is attached to the body- wall at the apex of the funnel, at a point which lies to the left of the duodenum. Up to this stage or to about the middle of the fourth month the mesentery has retained its attachment to the median line of the dorsal wall of the abdomen throughout its entire length, but later fusions of certain portions occur, whereby the original condition is greatly modified. One of the earliest of these fusions takes place at the apex Fig. 184. — Diagram show- ing the Arrangement of the Mesentery and Visceral Branches of the Abdominal Aorta in an Embryo of Six Weeks. p, Pancreas; S, stomach; Sp, spleen. — {Toldt.) THE PERITONEUM. 345 of the funnel, where the portion of the mesentery which passes to the transverse colon and arches over the duode- num fuses with the ventral surface of the latter portion of the intestine and also with the peritoneum covering the dorsal wall of the abdomen both to the right and to the left of the duodenum. In this way the attachment of the transverse mesocolon takes the form of a transverse line instead of a point, and this portion of the mesentery md Fig. 185. — Diagrams Illustrating the Development of the Great Omentum and the Transverse Mesocolon. bid, Caecum; dd, small intestine; dg, yolk-stalk; di, colon; du, duodenum; gc, greater curvature of stomach ; gg, bile duct ; g», great omentum ; k, point where the loops of the intestine cross ; mc, mesocolon ; md, rec- tum; mes, mesentery; wf, vermiform appendix. — (Hertwig.) divides the abdominal cavity into two portions, the upper (anterior) of which contains the liver and stomach, while the lower contains the remainder of the digestive tract with the exception of the duodenum. By passing across the ventral surface of the duodenum and fusing with it, the transverse mesocolon forces that portion of the intes- tine against the dorsal wall of the abdomen and fixes it in that position, and its mesentery thereupon degenerates, 29 346 THE DEVELOPMENT OF THE HUMAN BODY. becoming subserous areolar tissue, the duodenum assum- ing the retroperitoneal position which characterizes it in the adult. The descending colon, which on account of the width of its mesentery is at first freely movable, lies well over to the left side of the abdominal cavity, and in consequence the left layer of its mesentery lies in contact with the parietal layer of the peritoneum. A fusion of these two layers, beginning near the middle line and thence extend- Fig. 186. — Diagrams Illustrating the Manner in which the Fixation of the Descending Colon (Q takes Place. ing outward, takes place, the fused layers becoming con- verted into connective tissue, and this portion of the colon thus loses its mesentery and becomes fixed to the abdomi- nal wall. The process by which the fixation is accom- plished may be understood from the diagrams which constitute Fig. 1 86. When the ascending colon is formed, its mesentery undergoes a similar fusion, and it also be- comes fixed to the abdominal wall. The fusion of the mesentery of the ascending and descending colon remains incomplete in a considerable number of cases (one- THE PERITONEUM. 347 fourth to one- third of all cases examined), and in these the colons are not perfectly fixed to the abdominal wall. It may also be pointed out that the caecum and appendix, being pri- marily a lateral outpouching of the intestine, do not possess any true mesentery, but are completely enclosed by peritoneum. Usually a falciform fold of peritoneum may be found extending along one surface of the appendix to become continuous with the left layer of the mesentery of the ileum. This, however, is not a true mesentery, and is better spoken of as a mesenteriole. One other fusion is still necessary before the adult condi- tion of the mesentery is acquired. The great omentum consists of two folds of peritoneum which start from the greater curvature of the stomach and pass downward to be reflected up again to the dorsal wall of the abdomen, which they reach just anterior to (above) the line of attachment of the transverse mesocolon (Fig. 187, A). At first the attachment of the omentum is vertical, since it represents the mesogastrium, but later, by fusion with the parietal peritoneum it assumes a transverse direction, while at the same time the pancreas, which originally lay between the two folds of the mesogastrium, is carried dorsally and comes to have a retroperitoneal position in the line of attachment of the omentum. By this change the lower layer of the omentum is brought in contact with the upper layer of the transverse mesocolon and a fusion and degeneration of the two results (Fig. 187, B), a condi- tion which brings it about that the omentum seems to be attached to the transverse colon and that the pancreas seems to lie in the line of attachment of the transverse mesocolon. This mesentery, as it occurs in the adult, really consists partly of a portion of the original trans- verse mesocolon and partly of a layer of the great omen- tum. By these various changes the line of attachment of the mesentery to the dorsal wall of the body has become some- 348 THE DEVELOPMENT OF THE HUMAN BODY. what complicated and has departed to a very considerable extent from its original simple vertical arrangement. If all the viscera be removed from the body of an adult and the mesentery be cut close to the line of its attachment, the course of the latter will be seen to be as follows : De- scending from the under surface of the diaphragm are the Fig. 187. — Diagrams showing the Development of the Great Omen- tum and its Fusion with the Transverse Mesocolon. B, Bladder ; c, transverse colon ; d, duodenum ; Li, liver ; p, pancreas ; R, rectum; S, stomach; U, uterus. — (After Allen Thomson.) lines of attachment of the suspensory ligament, which on reaching the liver spread out to become the coronary and lateral ligaments of that organ. At about the mid-dorsal line these lines become continuous with those of the mesogastrium which curve downward toward the left and are continued into the transverse lines of the transverse THE SPLEEN. 349 mesocolon. Between these last, in a slight prolongation, there may be seen to the right the cut end of the first por- tion of the duodenum as it passes back to the dorsal wall of the abdomen, and at about the mid-dorsal line the cut ends of its last part become visible as it passes ventrally again to become the jejunum. From the transverse mesocolon three lines of attachment pass downward; the two lateral broad ones represent the lines of fixation of the ascending and descending colons, while the narrower median one, which curves to the right, represents the at- tachment of the mesentery of the small intestine other than the duodenum. Finally, from the lower end of the fixation line of the descending colon the mesentery of the sigmoid is continued downward. The Development of the Spleen. — The spleen has gen- erally been regarded as a development of the mesenchyme situated between the two layers of the mesogastrium. To this view, however, recent observers 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 mesen- chyme accompanied by a thickening of the coelomic epi- thelium which covers the elevation. The mesenchyme thickening presents no differences from the neighboring mesenchyme, but the epithelium is not distinctly sepa- rated from it over its entire surface, as it is elsewhere in the mesentery. In later stages, which have been ob- served in detail in pig and other amniote embryos, cells separate from the deeper layers of the epithelium (Fig. 1 88) and pass into the mesenchyme thickening, whose tissue soon assumes a different appearance from the sur- 3 50 THE DEVELOPMENT OF THE HUMAN BODY. rounding mesenchyme by its cells being much crowded. This migration soon ceases, however, and in embryos of forty-two days the ccelomic epithelium covering the thick- ening is reduced to a simple layer of cells. The later stages of development consist of an enlarge- ment of the thickening and its gradual constriction from the surface of the 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 differ- entiate themselves into trabecular and pulp cords, special collections of cells around the branches of the splenic artery forming the Malpighian corpuscles. Fig. 188. — Section through the Left Layer op the Mesogastrium of a Chick Embryo of Ninety-three Hours, showing the Origin of the Spleen. ep, Coelomic epithelium; ms, mesenchyme. — (Tonkoff.) It has already been pointed out (p. 244) that during embry- onic life the spleen is an important haematopoietic organ, both red and white corpuscles undergoing active formation within its substance. The Malpighian corpuscles are collections of lymphocytes in which multiplication takes place, and while nothing is as yet known as to the fate of the cells which are contributed to the spleen from the ccelomic 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. LITERATURE. 3 5 I LITERATURE. A. BrachET: " Die Entwickelung der grossen Korperhohlen und ihre Tren- nung von Einander," Ergebnisse der Anat. und Entwickelungsgesch., vil, 1898. W. His: " Mittheilungen zur Embryologie! der Saugethiere und des Mens- chen," Archiv fur Anat. und Physiol., Anat. Abth., 1881. F. P. Mali,: "Development of the Human Coelom," Journal of Morphol., xii, 1897. E. Ravn: "Ueber die Bildung der Scheidewand zwischen Brust- und Bauchhohle in Saugethierembryonen," Archiv fur Anat. und Physiol., Anat. Abth., 1889. A. Swaen: " Recherches sur le developpement du foie, du tube digestif, de l'arriere-cavitfi du peritoine et du mesentere," Journ. de I 'Anat. et de la Physiol., xxxn, 1896; xxxin, 1897. C. ToldT: " Bau und Wachsthumsveranderungen der Gekrose des mensch- lichen Darmkanals," Denkschr. der kais. Akad. Wissensch. Wien, Math.-Naturwiss. Classe t xu, 1879. C. ToldT: " Die Darmgekrose und Netze im gesetzmassigen und gesetzwi- drigen Zustand," Denkschr. der kais. Akad. Wissensch. Wien, Math.- Naturwiss. Classe, lvi, 1889. W. Tonkopf: "Die Entwickelung der Milz bei den Amnioten," Archiv fur mikrosk. Anat., i,vi, 1900. F. Treves : " Lectures on the Anatomy of the Intestinal Canal and Perito- neum," British Medical Journal, 1, 1885 CHAPTER XII. THE DEVELOPMENT OF THE ORGANS OF RESPIRATION. The Development of the Lungs. — The first indication of the lungs and trachea is found in embryos of about 3.2 mm. in the form of a groove on the ventral surface of the oesophagus, at first extending almost the entire length of that portion of the digestive tract. As the oesophagus lengthens the lung groove remains connected with its upper portion (Fig. 168, A), and furrows which ap- pear along the line of junction of the groove and the oesophagus gradu- ally deepen and separate the two structures (Fig. 168, B). The separation takes place earliest at the lower end of the groove and thence extends up- ward, so that the groove is transformed into a cyl- indrical pouch lying ven- trad of the oesophagus and dorsad of the heart and opening with the oesophagus into the terminal portion of the pharynx. Soon after the separation of the groove from the oesophagus its lower end becomes enlarged and bilobed, 352 RP Fig. 189. — Portion of a Section through an embryo . op the ^Fourth Week. A, Aorta; DC, ductus Cuvieri; L, lung; O, oesophagus; RP, parietal recess ; VOm, omphalo-mesenteric vein. — (Toldt.) THE LUNGS. 353 and since this lower end lies, with the oesophagus, in the median attached portion of the dorsal edge of the septum transversum, the lobes, as they enlarge, project into the dorsal parietal recesses (Fig. 189), and so become enclosed within the peritoneal lining of the recesses which later become the pleural cavities. The lobes, which represent the lungs, do not long remain simple, but bud-like processes arise from their cavities, three appearing in the right lobe and two in the left (Fig. Fig. 190. — Reconstruction of the Lung Outgrowths op Embryos op (A) 10, (B) 8.5, and (C) 10.5 mm. Ap, Pulmonary artery ; Ep, apical bronchus ; Vp, pulmonary vein ; I-II, primary bronchi. — {His.) 190, A), and as these increase in size and give rise to addi- tional outgrowths, the structure of the lobes rapidly be- comes complicated (Fig. : 1 90, B and. C) . In the formation of new outgrowths the terminal enlarged part of each pro- cess divides as if to give rise to two equal bronchi, but ' later as the new bronchi elongate, one grows more rapidly than the Other and places itself so as to be in the line of the stem from which it arose, its fellow seeming to be a lateral branch from it. As a result of this method of growth a 3° 354 THE DEVELOPMENT OF THE HUMAN BODY. main bronchus traversing the entire length of the lung is formed, and into it there open numerous lateral branches, which may be termed secondary bronchi, arranged in a more or less definite and similar manner in the two lungs. The main stem of the pulmonary artery traverses the lung lying to the outer side of the main bronchus, and since cer- tain of the secondary bronchi arise ventral and others dor- sal to the line of the artery it is possible to recognize series of ventral and dorsal bronchi. These alternate more or less regularly with one another, the dorsal bronchi stand- ing higher than the ventral and in the human lung there are usually four ventral bronchi, while the number of the dorsal ones is frequently reduced to three by the failure of the one corresponding to the third ventral to develop. The first dorsal bronchus of the left side differs from that of the right side in that it arises from the first ventral bronchus instead of from the main stem, a condition with which is associated the fusion of the upper and middle lobes of the left lung to a single lobe. The secondary branches elongate and give rise to lateral branches just as do the main bronchi, and of these tertiary bronchi one, which arises from the second ventral bron- chus or from the main bronchus in its neighborhood, is of especial importance, since, especially in the right lung, in which it is usually better developed than in the left, it frequently forms the main stem for a fourth lobe, which, from its position, is termed the injracardial lobe. At first the amount of mesenchyme which separates the various branches is comparatively great, but as the branchings continue, the growth of the mesenchyme fails to keep pace with it, so that in later stages the terminal enlargements are separated from one another by only very thin partitions of mesenchyme in which the pulmonary vessels form a dense network. The final branchings of THE LARYNX. 355 each ultimate bronchus or bronchiole results in the forma- tion at its extremity of from three to five enlargements, the atria (Fig. igi, A), from which arise a number of air- sacs or alveoli (s) whose walls are pouched out into slight diverticula, the air-cells. Such a combination of atria, air-sacs, and air-cells constitutes a lobule, and each lung is com- posed of a large number of such units. The greater part of the origi- nal pulmonary groove becomes converted into the trachea, and in the mesenchyme surrounding it the incomplete cartilaginous rings develop at about- the eighth or ninth week. The cells of the epithelial lining of the trachea and bronchi remain col- umnar or cubical in form and become ciliated at about the fourth month, but those of the epithelium of the air-sacs be- come greatly flattened and con- stitute an exceedingly thin layer of pavement epithelium. The Development of the Larynx. — The opening of the upper end of the pulmonary groove into the pharynx is situated at first just behind the fourth branchial furrow and is surrounded anteriorly and laterally by the ("I- shaped ridge already described (p. 31 1) as the furcula, this separating it from the posterior portion of the tongue (Fig. 164). The anterior portion of this ridge, which is appar- ently derived from the ventral portions of the third bran- chial arch, gradually increases in height and forms the Fig. 191. — Diagram of the Final Branches of the Mammalian Bronchi. A, Atrium; B, bronchus; 5, air-sac. — (Miller.) 356 THE DEVELOPMENT OF THE HUMAN BODY. epiglottis, while the lateral portions, which pass posteriorly into the margins of the pulmonary groove, form the aryte- noid ridges. When the pulmonary groove separates from the oesophagus, the opening of the trachea into the pharynx is somewhat slit-like and is bounded laterally by the aryte- noid ridges, whose margins present two elevations which may be termed the cornicular and cuneiform tubercles (Pig. 192, co and cu, and Fig. 161). The opening is, how- ever, for a time, almost obliterated by a thicken- ing of the epithelium covering the ridges, and it is not until the tenth or eleventh week of de- velopment that it is re- established. Later than this, at the middle of the fourth month, a linear depression makes its ap- pearance on the mesial wall of each arytenoid ridge, forming the begin- ning of the ventricle, and although at first the de- pression lies horizontally its lateral edge later bends anteriorly, so that its surfaces look outwards and inwards. The lips which bound the opening of the ven- tricle into the laryngeal cavity give rise to the vocal cords. The cartilages of the larynx can be distinguished during the seventh week as condensations of mesenchyme which are but indistinctly separated from one another. The thyreoid cartilage is represented at this stage by two lateral plates of mesenchyme, separated from one another both Fig. 192. — Reconstruction of the Opening into the Larynx in an Embryo of Twenty-eight Days, Seen from Behind and Above, the Dorsal Wall of the Pharynx be- ing Cut Away. co, Cornicular, and cu, cuneiform tubercle; Ep, epiglottis; T, unpaired portion of the tongue. — (Kallius.) THE LARYNX. 357 ventrally and dorsally, and each of these plates undergoes chondrification from two separate centers (Fig. 193). These, as they increase in size, unite together and send prolongations ventrally which meet in the mid-ventral line with the corresponding prolongations of the plates of the opposite side, so as to enclose an area of mesenchyme into which the chondrification only extends at a later period, and occasionally fails to so extend, producing what is termed a foramen thyreoideum. The mesenchymal condensations which represent the cricoid and arytenoid cartilages are continuous, but each Fig. 193. — Reconstruction of the Mesenchyme Condensations which Represent the Hyoid and Thyreoid Cartilages in an Embryo op Forty Days. The darkly shaded areas represent centers of chondrification. c.ma, Greater cornu of hyoid; c.mi, lesser cornu; Th, thyreoid cartilage. — (Kallius.) arytenoid has a distinct center of chondrification, while the cartilage of the cricoid appears as a single ring which is at first open dorsally and only later becomes complete. The epiglottis, cartilage resembles the thyreoid in being formed by the fusion of two originally distinct cartilages, from each of which a portion separates to form the cunei- form cartilages (cartilages of Wrisberg) , while the cornic- ulse laryngis (cartilages of Santorini) are formed by the separation of a small portion of cartilage from each aryte- noid. 358 THE DEVELOPMENT OF THE HUMAN BODY. The formation of the thyreoid cartilage by the fusion of two pairs of lateral elements finds an explanation from the study of the comparative anatomy of the larynx. In the lowest group of the mammalia, the Monotremata, the four cartilages do not fuse together and are very evidently serially homologous with the cartilages which form the cornua of the hyoid. In other words, the thyreoid results from the fusion of the fourth and fifth branchial cartilages. The cricoid, in its development, presents such striking similarities to the cartilaginous rings of the trachea that it is probably to be regarded as the uppermost cartilage of that series, but the paired arytenoids and the epiglottis are possibly representatives of the sixth and seventh pairs of branchial cartilages, structures which occur with great constancy in the lower vertebrates. The epiglottis possibly represents the sixth pair of cartilages and the arytenoids the seventh (Gegenbaur). These two last arches have undergone almost complete reduction in the mammalia, the cartilages being their only representatives, but, in addition to the cartilages, the fourth and fifth arches have also preserved a portion of their musculature, part of which becomes transformed into the muscles of the larynx. Since the nerve which corresponds to these arches is the vagus, the supply of the larynx is derived from that nerve, the superior laryngeal nerve probably corresponding to the fourth arch, while the inferior (recurrent) answers to the fifth. The course of the recurrent laryngeal nerve finds its explana- tion in the relation of the nerve to the fourth branchial artery. When the heart occupies its primary position ventral to the floor of the pharynx, the inferior laryngeal nerve passes transversely inward to the larynx beneath the fourth branchial artery. As the heart recedes the nerve is caught by the vessel and is carried back with it, the portion of the vagus between it and the supe- rior laryngeal nerve elongating until the origins of the two LITERATURE. 359 laryngeal nerves are separated by the entire length of the neck. Hence it is that the right recurrent nerve bends upward behind the right subclavian artery, while the left curves beneath the arch of the aorta (see Fig. 139). LITERATURE. E. GoppERT: " Ueber die Herkunft der Wrisbergschen Knorpels," Morphol. Jahrbuch, xxi, 1894. W. His: "Zur Bildungsgeschichte der Lungen beim menschlichen Em- bryo," Archix jilr Anat. und Physiol., Anat. Abth., 1887. E. Kaiaius: "Beitrage zur Entwickelungsgeschichte des Kehlkopfes," Anat. Hefte, IX, 1897. E. Kaiaius: "Die Entwickelung des menschlichen Kehlkopfes," Ver- handl. der Anat. Gesellsch., xn, 1898. A. Narath: "Der Bronchialbaum der Saugethiere und des Menschen," Bibliotheca. Medica, Abth. A, Heft 3, 1901. CHAPTER XIII. THE DEVELOPMENT OF THE URINOGENITAL SYSTEM AND THE SUPRARENAL BODIES. The excretory and reproductive systems of organs are so closely related in their development that they must be considered together. They both owe their origin to the mesoderm which constitutes the intermediate cell-mass, this, at an early period of development, becoming thick- ened so as to form a ridge projecting into the dorsal por- nc Fig. 194 — Transverse Section through the Abdominal Region op a Rabbit Embryo of 12 mm. a, Aorta ; g/, glomerulus ; gr, genital ridge ; m, mesentery ; nc, notochord ; t, tubule of mesonephros; wd, Wolffian duct; wr, Wolffian ridge. — (Mihalkovicz.) tion of the ceelom and forming what is known as the Wolf- fian ridge (Fig. 194, wr). The greater portion of the sub- stance of this ridge is concerned in the development of the primary and secondary excretory organs, but on its mesial surface a second ridge appears which is destined to give rise to the ovary or testis, and hence is termed the genital ridge (g). 360 THE PRONEPHROS. 36 1 The development of the excretory organs is remarkable in that three sets of organs appear in succession. The first of these, the pronephros, exists in a very rudimentary condition in the human embryo, although its duct, the pronephric or Wolffian duct, undergoes complete develop- ment and plays an important part in the development of the succeeding organs of excretion and also in that of the reproductive organs. The second set, the mesonephros or Wolffian body, reaches a considerable development dur- ing embryonic life, but later, on the development of the final set, the definitive kidney or metanephros, undergoes degeneration, portions only persisting as rudimentary structures associated for the most part with the reproduc- tive organs. The Development of the Pronephros and the Proneph= ric Duct. — The first portions of the excretory system to make their appearance are the pronephric or Wolffian ducts, and these develop as thickenings of the lateral parts of the intermediate cell-masses. At first the thickenings form solid cords of cells (Fig. 195, wd), but later a lumen appears in the center of each cord, which thus becomes converted into a canal. Ih early stages the cords, toward their posterior ends, may undergo a secondary fusion with the immediately overlying ectoderm (Martin) and may thereby present the appearance of having arisen from that layer, but when fully developed the ducts lie in the sub- stance of the Wolffian ridges (Fig. 194, wd), their anterior ends being situated well forward in the region occupied by the heart, whence they extend backward to open on the ventral part of the lateral walls of the cloaca (Fig. 156). The pronephros appears in embryos of about 3 mm. as two tubular invaginations of the coelomic epithelium into the substance of each Wolffian ridge, in the region in which the anterior end of the Wolffian duct is found (Janhosik) . 362 THE DEVELOPMENT OF THE HUMAN BODY. The tubules do not proceed to complete development, making no connection with the duct, and indeed the ante- rior one hardly deserves to be termed a tubule, since it is a solid cord of cells, continuous at one extremity with the coelomic epithelium. The posterior one is, however, a hollow tubule ending blindly at one extremity, while at the other it communicates with the ccelomic cavity, the opening being termed a nephrostome. Opposite these ru- dimentary tubules there arises from the root of the mesen- tery a process which projects freely into the coelom toward the nephrostomes. This probably represents a rudimen- im tic Fig. 195. — Transverse Section through Chick Embryo of about Thirty-six Hours. en, Endoderm ; im, intermediate cell mass ; ms, mesodermic somite ; nc, notochord ; so, somatic, and sp, splanchnic mesoderm ; wd, Wolffian duct . — ( Waldeyer.) tary free glomerulus, into which branches from the aorta may project. Nothing is known as to the further development of these pronephric tubules and glomeruli, but it seems probable that they are merely transitory structures which disap- pear completely at an early stage of development (see P-39 1 )- A similar but more perfectly developed pronephros has been described in other mammals, such as the rabbit and rat, and is of constant occurrence in all the lower vertebrates. In these the pronephric tubules, which may be six (in the lamprey) or more in number on each side, are primarily arranged segment- THE MESONEPHROS. 363 ally, and open by one extremity into the anterior portion of the Wolffian duct and by the other into the ccelomic cavity, and, furthermore, each tubule has corresponding to it a glomerulus which lies freely in the coelomic cavity in the vicinity of the nephrostome. By these free glomeruli and by the possession of nephrostomes the tubules of the pronephros are distinguished from those of the mesonephros in the higher vertebrates, and since both these peculiarities are represented in the two pairs of tubules described above as occurring in the 3 mm. human em- bryo, there seems to be little room for doubt but that they are representatives of a rudimentary pronephros. It has been very generally supposed that the tubules of the mesonephros, which develop in the segments succeeding those which contain the pronephros, were serially homologous with the pronephric tubules. Doubts have recently been aroused against this theory (Riickert, Wheeler). Important structural differences exist in the two sets of tubules, and since even in the lowest vertebrates the pronephros seems to be a rudimentary structure, it has been held not improbable that in the ancestors of the vertebrates it was a much more perfectly developed organ, extending back into the region occupied by the mesonephros in existing vertebrates. As the mesonephros developed the pro- nephros underwent degeneration, portions of its tubules per- sisting, however, and uniting to form a continuous canal, the pronephric duct, a structure for which, otherwise, it is difficult to find a satisfactory explanation. The fact that in lower forms the duct seems to develop as a number of separate parts which later become continuous stands in favor of this hypothesis, but in opposition to it is the observation that the lower portion of the duct in several species of mammals arises from the ectoderm (von Spee, Flemming). It seems, however, to be established that in the majority of the lower vertebrates it is of purely mesodermal origin, and its connection with the ectoderm in the mammalia is therefore very probably due to a secondary fusion (Martin). The Development of the Mesonephros. — The pronephric duct does not disappear with the degeneration of the pro- nephric tubules, but persists to serve as the duct for the mesonephros and to play an important part in the devel- opment of the metanephros also. In the regions of the Wolffian ridge which lie posterior to the pronephros there 364 THE DEVELOPMENT OF THE HUMAN BODY. appear in embryos of between 3 and 4 mm. a number of coiled tubules whose origin has not yet been sufficiently elucidated in human embryos. In lower mammals they arise by some of the cells of the Wolffian ridge aggregating together to form solid cords, which are entirely uncon- nected with the coelomic epithelium and at first also with the Wolffian (pronephric) duct. These cords acquire a lumen and at one end connect with the duct, while near the other end a condensation of the mesoderm of the ridge occurs to form a glomer- ulus into which a vessel extends from the neigh- boring aorta. The tu- bules rapidly increase in length and become coiled, and the glomeruli project into their cavi- ties, pushing in front of them the wall of the tu- bule so that the whole structure has the ap- pearance represented in Fig. 196. It seems probable that primarily the mesoneph- ric cords are arranged segmentally, a single pair occurring in each segment of the body behind the pronephros as far back, probably, as the pelvic region, and hence the inter- mediate cell-mass from which the Wolffian ridge is formed may properly be regarded as composed of nephrotomes, even though no surface indications of segmentation are to be seen in it. The correspondence of the tubules with the myotomes becomes, however, early disturbed, partly as the result of differences in growth of the two structures, Fig. 196. — Transverse Section of the Wolffian Ridge of a Chick Embryo of Three Days. ao, Aorta; gl, glomerulus; gr, genital ridge ; mes, mesentery ; mt, meso- nephrie tubule ; vc, cardinal vein ; Wd, Wolffian duct. — (Mihalkovicz.) THE MESONEPHROS. 365 but especially because a number of secondary and tertiary tubules develop in connection with each of the primary ones. Exactly how these additional tubules arise is a little uncertain, some observers maintaining that they are formed from the substance of the Wolffian ridge in the same manner as the primary tubules with which they later '-—md nd Fig. 197. — Urinogenital Apparatus op a Male Pig Embryo of 6 cm. ao, Aorta; b, bladder; gh, gubernaculum of Hunter; k, kidney; md, Mullerian duct; sr, suprarenal body; t, testis; -w, Wolffian body; wd, Wolffian duct. — (Mihalkovicz.) become connected (Mihalkovicz), while others hold that they are formed by the splitting of the primary tubules or as buds from these (Braun, Janhosik). By the formation of these additional tubules and the continued elongation of all, whereby they become thrown into numerous convolutions, the Wolffian ridge becomes a somewhat voluminous structure, projecting markedly 366 THE DEVELOPMENT OF THE HUMAN BODY. into the coelomic cavity (Fig. 197). It is attached to the dorsal wall of the body by a distinct mesentery and has in its lateral portion, embedded in its substance, the Wolffian duct, while on its mesial surface anteriorly is the but slightly developed genital ridge (t). This condition is reached in the human embryo at about the sixth or seventh week of development, and after that period the mesonephros undergoes rapid degeneration, so that at about the sixteenth week nothing remains of it except the duct and a few small rudiments whose history will be given later. The Development of the Metanephros. — The meta- nephros arises as an outgrowth from the dorsal surface of the Wolffian duct, shortly before its entrance into the cloaca (Fig. 156). The outgrowth is of a tubular form and, as it elongates, it comes to lie dorsal to the mesonephros, its anterior end enlarging and becoming lobed and also becoming surrounded by a condensation of mesenchyme which has been termed the metanephric blastema. The outgrowth, which represents the ureter, makes its appear- ance in embryos of about 5 mm., but its anterior end does not reach its final position in the neighborhood of the suprarenal body until the third month of development. The development of the tubules of the metanephros has been studied most thoroughly in the rabbit, and the description which follows is based on what occurs in that animal. The extremity of the ureter early begins to branch within the substance of the blastema, and in em- bryos of twelve days it has given rise to two or three branches which branch again, each of the terminal branches ending in a distinct enlargement, a primary renal vesicle, which lies in the cortical portion of the blas- tema which by this time has formed a capsule for itself (Fig. 198, A). In embryos one day older each of the renal THE METANEPHROS. 367 vesicles has given rise to two or three prolongations which are coiled upon themselves in an S-shaped manner and represent urinary tubules (Figs. 198, B, and 199, A). In what would correspond with the lower loop of the S, a collection of mesenchyme appears into which at a later stage branches penetrate from the renal artery, producing a glomerulus, the wall of the tubule in this region becom- ing exceedingly thin to form a capsule of Bowman (Fig. 199, B, be). At first the glomerulus lies close to the surface of the kidney, but as development proceeds it is gradu- ally carried deeper into the cortical por- tion by the elongation of the portion of the tubule intervening be- tween the glomerulus and the primary renal vesicle. This elonga- tion affects at first the upper limb of the S, which is represented by the loop of Henle in the adult kidney, the portion between the loop and the glomerulus forming the first, and that between the loop and the renal vesicle the second, convoluted tubule (Fig. 199, Q. In the mean time new tubules have arisen from the vesicle and have undergone a development similar to what occurs in the earlier formed ones, and the formation of new tubules continues until a large number has been pro- duced from each renal vesicle, these eventually elongating to form the collecting tubules (Fig. 199, C). Up to the Fig. 198. — Diagrams of Early Stages in the Development of the Meta- nephric Tubules. t, Urinary tubule; Ur, ureter; v, renal vesicle. — (Haycraft.) 3 68 THE DEVELOPMENT OF THE HUMAN BODY. time when the urinary tubules begin to develop there is no pelvis to the kidney, the ureter extending well toward the center of the blastema before beginning to branch and the branches thence extending to the cortex (Fig. 198). As soon as the tubules appear, however, the formation of the pelvis begins by what has been described as an evagination of the primary branches of the ureter to form a common cavity, a process which is beginning to &c f Fig. 199. — Three Stages in the Development of a Urinferous Tubule of a Rabbit. 6c, Bowman's capsule; g, glomerulus; /;, loop of Henle; V, renal vesicle. — (Haycraft.) manifest itself in the stage shown in Fig. 198, B, and which is continued until the secondary branches are also taken up into the cavity, into which the various collecting tubules then open separately. At about the tenth week of development the surface of the human kidney becomes marked by shallow depressions into lobes, of which there are about eighteen, one corre- THE MULLERIAN DUCT. 369 sponding to each of the groups of tubules which arise from the same renal vesicle. This lobation persists until after birth and then disappears completely, the surface of the kidney becoming smooth. From what has been said above it will be seen that the tubules of the metanephros are all derived from the original outgrowth which arises from the Wolffian duct; the tissue of the meta- nephric blastema gives rise only to the connective tissue and vessels of the kidney. It was at one time maintained that the ureters and collecting tubules were alone developed from the outgrowth, and that the tubules were formed independently in the blastema and only later united with the collecting tubules. The view presented above seems, however, to more nearly repre- sent the actual processes of development. The Development of the Miillerian Duct and of the Qeni= tal Ridge. — At the time when the Wolffian body has al- most reached its greatest development a second longitudi- nal duct makes its appearance in close proximity to the Wolffian. This is known as the Miillerian duct (Fig. 200, Md). Its development is preceded by the appearance of a distinct ridge or fold upon the ventral surface of the Wolffian body, extending from the under surface of the diaphragm above to the urogenital sinus below and con- taining in the lower portion of its course the Wolffian duct (Fig. 197). Near the anterior end of the mesoneph- ros there grows into this fold an evagination from the peritoneum covering the Wolffian ridge and by the pro- liferation of the cells at its tip this evagination gradually extends downward in the substance of the ridge, and in embryos of 22 mm. has reached the urogenital sinus. As they approach the sinus, the right and left evaginations or Miillerian ducts gradually approach one another and finally fuse together to form a single tube in the lower part of their course, but they remain distinct above, each tube retaining its original opening into the peritoneal cavity. 31 37° THE DEVELOPMENT OF THE HUMAN BODY. Fig. 200. — Transverse Section through the Abdominal Region of an Embryo of 25 mm. Ao, Aorta; B, bladder; /, intestine; L, liver; M, muscle; Md, Miillerian duct; N, spinal cord; Ov, ovary; RA, rectus abdominis; Sg, spinal ganglion; UA, umbilical artery; Ur, ureter; v, vertebra; W, Wolffian body; Wd, Wolffian duct. — (Keibel.) THE GENITAL RIDGE. 37 1 The first indication of the appearance of the genital ridge is the assumption of a high columnar form by the epithelial cells of the upper part of the mesial surface of the Wolffian ridge, and shortly after this thickening of the epithelium has appeared a condensation of the underlying mesenchyme occurs (Fig. 194). At first the ridge is of insignificant dimensions compared with the more vol- uminous Wolffian body, but as the degeneration of the latter proceeds the relative size of the two structures be- comes reversed and the genital ridge forms a marked prominence attached to the surface of the Wolffian ridge by a fold of peritoneum which becomes the mesovarium in the female and the mesorchium in the male. The fold which surrounds the Wolffian body becomes transformed on the degeneration of that structure into the broad liga- ment, the transverse position of which in the adult is due' to the fusion of the lower portions of the Miillerian ducts, and since the genital ridges lie primarily to the median side of the ducts, they come to be attached by their mesen- tery to the dorsal surface of the broad ligament. The relations of the broad ligaments and mesorchia in the male become profoundly modified by the descent of the testes into the scrotum, a process to be described later (p. 388.) From each genital ridge a prolongation of mesenchyme extends downward in the mesentery of the ridge, nearly parallel with the Miillerian duct, with which it comes into contact at the point where the two ducts fuse and thence is continued downward and forward between the folds of the broad ligament to be attached to the ventral wall of the abdomen in the inguinal region. The upper part of this prolongation of the genital ridge represents the liga- ment of the ovary and its lower part the ligamentum teres of the female (Fig. 201), while in the male the entire struc- ture forms what is known as the gubemaculum testis. 372 THE DEVELOPMENT OF THE HUMAN BODY. Although the histological differentiation of the genital ridge proceeds along similar lines in both sexes until about the fifth or sixth week, it seems convenient to consider separately the entire process of differentiation as it occurs in each sex. The Development of the Testis. — The earliest sign of de- velopment visible in the testis is a multiplication of the epithelial cells to form a thick layer, into the under surface of which deep bays extend from the subjacent mesen- chyme, producing the appear- ance of cords of cells extend- ing into the mesenchyme from the epithelium. These cords (Fig. 202, ec) consist of two kinds of cells, (1) elongated cells with a small amount of protoplasm, the epithelial cells, and (2) large spherical cells with more abundant, clear protoplasm, and termed sexual cells. While the development is at this stage, — that is, at about the fourth or fifth week, — a structure makes its appearance which serves to characterize the organ as a testis. This is a layer of connective tissue which grows in between the superficial and deep layers of the epithelium and gradually extends around the entire organ to form the tunica albuginea. Shortly after its appearance the cords of cells become broken up into more or less spherical masses by the growth into them of the surrounding mesen- Fig. 201. — Reproductive Or- gans of a Female Embryo of Six Months. B, Bladder ; F, Fallopian tube ; /, intestine; 01, ovarian liga- ment; Ov, ovary; Rl, round ligament; UA, umbilical ar- tei y ; Ur, ureter ; Ut, uterus ; W, Wolffian body (epoopho- ron). — (Adapted from Mihal- kovicz.) THE TESTIS. 373 chyme, and into the substance of the testis there grow from the capsules of Bowman in the neighboring portions of the mesonephros cords of cells which form what are known as the medullary cords (Fig. 202, mc). One of these cords comes into relation with each of the spherical masses derived from the epithelium, and the cells of each mass, both the epithelial and the sexual, arrange themselves in a layer surrounding the enclosing wall of mesenchyme, al- f£?J\ Fig. 202. — Section through the Testis and the Broad Ligament op the Testis of an Embryo of 5.5 mm. ec, Epithelial cords ; ep, epithelium ; mc, medullary cords ; mi, Miillerian duct; mo, mesorchium; wd, Wolffian duct. — (Mihalkovicz.) though no lumen as yet occurs in any of them. This con- dition is reached at about the sixth week, and from this time onward until the approach of puberty, the changes which occur are limited to a growth in length of the med- ullary cords and epithelial masses, lumina not appearing in them until shortly before puberty. As this period approaches the final differentiation of the testis is completed. A lumen appears in each epithelial 374 THE DEVELOPMENT OF THE HUMAN BODY. mass, which thus becomes a tubule, and the medullary cords are also transformed into tubules. The sexual cells begin to multiply and assume the form of spermatogonia (see p. 30), while the epithelial cells become transformed into Sertoli cells (Benda). There is some difference of opinion as to whether the medullary cords take any part in the formation of the seminiferous tubules of the adult testis; the probability seems to be in favor of the view that they do not, the seminiferous tubules being derived from the epithelial cords alone, while the medullary cords give rise to the tubuli recti and the capsules of Bowman from which they arise to the rete testis. The Development of the Ovary. — The development of the ovary starts off on the same general lines as that of the testis, although there are important differences in the de- tails. Two distinct elements are concerned, as in the case of the testis — namely, cords of cells derived from the epithelium of the genital ridge and prolongations from the uppermost tubules of the mesonephros ; but the relations of the two elements and their differentiation are very different in the ovary. The ovarial epithelial cords when fully developed con- sist of three well-defined portions: (1) a lower rather cylindrical portion, (2) an intermediate short and greatly thickened portion, and (3) an outer short cylindrical por- tion or neck (Fig. 203). Each cord so constituted corre- sponds to one of the epithelial cords of the testis, but whereas in the latter epithelial and sexual cells occur throughout the entire length of the cord, in the ovary the sexual cells are found only in the intermediate en- largement. At an early stage the lower cylindrical portions of the ovarial cords become separated from the interme- diate portions by connective tissue and form what have been termed the medullary cords, though it is clear that THE OVARY. 375 they are not homologous with the structures so named in the testis. After this separation the intermediate portion of each cord is penetrated by bands of mesenchyme in such a manner that it becomes divided into secondary cylindrical cords known as Pfliiger's cords (Fig. 204), and these latter again be- come divided transversely into rounded masses, the Graafian follicles, each of which contains, as a rule, but a single sexual Fig. 203. — Diagram of an Epithelial In- vagination of the Ovary of a Rabbit. ep, Ovarial epithelium ; e, intermediate enlarge- ment containing germ cells ; i, proximal cyl- indrical portion ; me, medullary cord. — {von Winiwarter.) Fig. 204. — Section of the Ovary of a New-born Child. a, Ovarial epithelium ; b, proximal part of an epithelial cord ; c, germ cell in epithelium; d, intermediate enlarge- ment of an epithelial cord ; e, group of germ cells enclosed in a follicle ; /, single germ cells with follicles ; g, blood-vessel. — (From Gegcnbaur, after Waldeyer.) cell which is enclosed within a mass of epithelial cells, the whole being surrounded by a condensed zone of 37^ THE DEVELOPMENT OF THE HUMAN BODY. mesenchyme, which eventually becomes richly vascular- ized and forms the theca folliculi (Fig. 9). The epithe- lial cells in each follicle are at first comparatively few in number and closely surround the sexual cell (Fig. 204, e) which is destined to become an ovum, but in certain of the follicles they undergo an increase by mitosis, be- coming extremely numerous, and later secrete a fluid, the liquor folliculi, which collects at one side of the follicle and eventually forms a considerable portion of its con- tents. The follicular cells are differentiated by its ap- pearance into the stratum granulosum, which surrounds the wall of the follicle, and the discus proligerus, in which the ovum is embedded (Fig. 9, dp), and the cells which immediately, surround the ovum, becoming cylindrical in shape, give rise to the corona radiata (Fig. 10, cr). The elements derived from the mesonephros which correspond to the medullary cords of the testis do not reach as extensive a development as in that organ and, indeed, do not really penetrate into the substance of the ovary, but form a network, the rete ovarii, lying in the mesovarium along the line of its junction with the ovary. In some mammals, such as the rabbit, they come into contact with the so-called ovarian medullary cords, the similarity to the conditions obtaining in the testis being thus greatly increased. The Transformation of the Mesonephros and the Ducts. — At one period of development there are present, as rep- resentatives of the urinogenital apparatus, the Wolffian body (mesonephros) and its duct, the Miillerian duct, and the developing ovary or testis. Such a condition forms an indifferent stage from which the development proceeds in one of two directions according as the genital ridge be- comes a testis or an ovary, the Wolffian body in part undergoing degeneration and in part persisting to form THE TRANSFORMATION OF THE MESONEPHROS. UJ organs which for the most part are rudimentary, while in the female the Wolffian duct also degenerates except for certain rudiments and in the male the Mtillerian duct behaves similarly. In the Male. — It has been seen that the upper portion of the Wolffian body, in giving rise to the medullary cords of the testis, enters into very intimate relations with that organ and may be regarded as divided into two portions, an upper genital and a lower excretory. In the male the genital portion of the body persists in its entirety, serving as the efferent ducts of the testis, which, beginning in the spaces of the rete testis, already shown to represent the capsules of Bowman, open into the upper part of the Wolf- fian duct and form the globus major of the epididymis. The excretory portion undergoes extensive degeneration, a portion of it persisting as a mass of coiled tubules ending blindly at both ends, situated near the head of the epididy- mis and known as the paradidymis or organ of Giraldes, while a single elongated tubule, arising from the portion of the Wolffian duct which forms the globus minor of the epididymis, represents another portion of it and is known as the vas aberrans. The Wolffian duct is retained complete, the portion of it nearest the testis becoming greatly elongated and thrown into numerous coils, forming the body and globus minor of the epididymis, while the remainder of it is con- verted into the vas deferens and the ductus ejaculatorius. A lateral outpouching of the wall of the duct to form a longitudinal fold appears at about the third month and gives rise to the vesicula seminalis, the lateral position of the outgrowth explaining the adult position of the vesi- culae lateral to the vasa deferentia. With the Mullerian duct the case is very different, since it disappears completely throughout the greater part of its 32 378 THE DEVELOPMENT OF THE HUMAN BODY. course, only its upper and lower ends persisting, the former giving rise to a small sac-like body, the sessile hydatid of Morgagni, attached to the upper end of the FEMALE INDIFFERENT MALE Fig. 205. — Diagrams Illustrating the Transformations of the MullErian and Wolffian Ducts. B, Bladder; C, clitoris; CG, canal of Gaertner; CI, cloaca; Eo, epo- ophoron; Ep, epididymis; F, Fallopian tube; G, genital gland; HE, hydatid of epididymis; HM, hydatid of Morgagni; A", kidney; MD, Miillerian duct ; 0, ovary ; P, penis ; Po, paroophoron ; Pr, prostate gland; R, rectum; T, testis; U, urethra; UM, uterus masculinus ; Ur, ureter; US, urogenital sinus; Ul, uterus; V, vagina; VA, vas aberrans; VD, vas deferens; VS, vesicula seminalis; WB, Wolffian body; WD, Wolffian duct. — {Modified from Huxley.) testis near the epididymis, while the latter is represented by a depression in the floor of the urethra known as the THE TRANSFORMATION OF THE MESONEPHROS. 379 sinus pocularis, which is usually prolonged upward into a short cylindrical pouch known as the uterus masculinus, though it corresponds to the vagina rather than to the uterus of the female. In the Female. — In the female the genital portion of the mesonephros, though never functional as ducts, persists as a group of ten to fifteen tubules, situated between the two layers of the broad ligament and in close proximity to the ovary; these constitute what is known as the epo- ophoron {parovarium or organ of Rosenmiiller) . The tu- bules end blindly at the ends nearest the ovary, but at the other end, where they are somewhat coiled, they open into a collecting duct which represents the upper end of the Wolffian duct. Near this rudimentary body is another, also composed of tubules, representing the remains of the excretory portion of the mesonephros and termed the paroophoron. So far as the mesonephros is concerned, therefore, the persisting rudiments in the female are com- parable to those occurring in the male. As regards the ducts, however, the case is different, for in the female it is the Mullerian ducts which persist, while the Wolffians undergo degeneration, a small portion of their upper ends persisting in connection with the epo- ophora, while their lower ends persist as straight tubules lying at the sides of the vagina and forming what are known as the canals of Gartner. The Mullerian ducts, on the other hand, become converted into the Fallopian tubes, and in their lower portions into the uterus and vagina. From the margins of the openings by which the Mullerian ducts communicate with the coelom projections develop at an early period and give rise to the fimbrice, with the exception of the one connected with the ovary, the fimbria ovarica, which is the upper persisting portion of the original genital ridge, its lower portion, below the ovary, being represented by the ovarian and inguinal 38o THE DEVELOPMENT OF THE HUMAN BODY. ligament already described. It has been seen that the lower portions of the Mullerian ducts fuse together to form a single canal, and it is from this that the uterus and vagina are differentiated, the histological distinction of the two portions commencing to manifest itself at about the third month. During the fourth month the vaginal por- tion of the duct becomes flattened and the epithelium lining its lumen fuses so as to completely occlude it and, a little later, there appears near its lower opening a dis- tinct semicircular fold attached to its dorsal margin. This is the hymen, a structure which seems to be represented in the male by the veru montanum. The obliteration of the lumen of the vagina persists until about the sixth month, when the cavity is re-established by the breaking down of the central epithelial cells. The diagram, Fig. 205, illustrates the transformation from the indifferent condition which occurs in the two sexes, and that the homologies of the various parts may be clearly understood they may also be stated in tabular form as follows : Indifferent Stage. Male. Female. Genital ridge, < Testis. Gubernaculum. < Fimbria ovarica. Ovary. Ovarian ligament. Round ligament. Globus major of epididymis. Paradidymis. Vasa aberrantia. Epoophoron. Paroophoron. Wolffian ducts, / Body and globus mi- nor of epididymis. Vasa deferentia. Ejaculatory ducts. Collecting tubules of epoophoron. Canals of Gartner. Mullerian ducts -j Sessile hydatid. Uterus masculinus. Fallopian tubes. Uterus. Vagina. THE BLADDER. 38 I In addition to the sessile hydatid, a stalked hydatid also occurs in connection with the testis, and a similar structure is attached to the fimbriated opening of each Fallopian tube. The signifi- cance of these structures is uncertain, though it has been sug- gested that they are persisting rudiments of the pronephros. A failure of the development of the various parts just de- scribed to be completed in the normal manner leads to various abnormalities in connection with the reproductive organs. Thus there may occur a failure in the fusion of the lower por- tions of the Miillerian ducts, a bihorned or bipartite uterus re- sulting, or the two ducts may come into contact and their adja- cent walls fail to disappear, the result being a median partition separating the vagina or both the vagina and uterus into two compartments. The excessive development of the fold which gives rise to the hymen may lead to a complete closure of the lower opening of the vagina, while, on the other hand, a failure of the Miillerian ducts to fuse may produce a biperforate hymen. The Development of the Urinary Bladder and the Uro= genital Sinus. — So far the relations of the lower ends of the urinogenital ducts have not been considered in detail, al- though it has been seen that in the early stages of develop- ment the Wolffian and Miillerian ducts open into the sides of the ventral portion of the cloaca ; that the ureters com- municate with the lower portions of the Wolffian ducts; that from the ventral anterior portion of the cloaca the allantoic duct extends outward into the belly-stalk; and, finally (p. 297), that the cloaca becomes divided into a dorsal portion, which forms the lower part of the rectum, and a ventral portion, which is continuous with the allan- tois and receives the urinogenital ducts (Fig. 206). It is the history of this ventral portion of the cloaca which is now to be considered. It may be regarded as consisting of two portions, an anterior and a posterior, the line of insertion of the urino- genital ducts marking the junction of the two. The ante- rior or upper portion is destined to give rise to the urinary 382 THE DEVELOPMENT OF THE HUMAN BODY. bladder (Fig. 206, b), while the lower one forms what is known for a time as the urogenital sinus (sg). The bladder, when first differentiated, is a tubular structure, whose lu- men is continuous with that of the allantois, but after the second month it enlarges to become more sac-like, while the intra-embryonic portion of the allantois degenerates to a solid cord extending from the apex of the bladder to the Fig. 206. — Reconstruction of the Cloacal Region of an Embryo of 14 MM. al, Allantois; 6, bladder; gt, genital tubercle; i, intestine; n, spinal cord; nc, notochord ; r, rectum ; sg, urinogenital sinus ; ur, ureter ; w, Wolf- fian duct. — (Keibel.) umbilicus and is known as the urachus. During the en- largement of the bladder the terminal portions of the urinogenital ducts become taken up into its walls, a pro- cess which continues until finally the ureters and Wolffian ducts open into it separately, the ureters opening to the sides of and a little anterior to the ducts. This condition is reached in embryos of about 14 mm. (Fig. 206), and in THE URETHRA. 3 S 5 0"J later stages the interval between the two pairs of ducts is increased (Fig. 207), resulting in the formation of a short canal connecting the lower end of the bladder which re- ceives the ureters with the upper end of the urogenital sinus, into which the Wolffian and Miillerian ducts open. This connecting canal represents the urethra (Fig. 207, ur), or rather the entire urethra of the female and the Fig. 207. — Reconstruction of the Cloacal Structures op an Em- bryo of 25 MM. bl, Bladder; m, Miillerian duct; r, rectum; sg, urogenital sinus; sy, sym- physis pubis; H, ureter; ur, urethra; w, Wolffian duct. — (Adapted from Keibel.) proximal part of that of the male, since a considerable portion of the latter canal is still undeveloped (see p. 386). From this urethra there is developed, at about the third month, a series of solid longitudinal folds which project upon the outer surface and separate from the urethra from above downward. These represent the tubules of the 384 THE DEVELOPMENT OF THE HUMAN BODY. prostate gland and are developed in both sexes, although they remain in a somewhat rudimentary condition in the female. The muscular tissue, so characteristic of the gland in the adult male, is developed from the surrounding mesenchyme at a later stage. The urogenital sinus is in the early stages also tubular in its upper part, though it expands considerably below, where it is closed by the cloacal membrane. This, by the separation of the cloaca into rectum and sinus, has be- come divided into two portions, the more ventral of which closes the sinus and the dorsal the rectum, the interval be- tween them having become considerably thickened to form the perineal body. In embryos of about 1 7 mm. the urogenital portion of the membrane has broken through, and in later stages the tubular portion of the sinus is gradually taken up into the more expanded lower portion, until finally the entire sinus forms a shallow depression, termed the vestibule, into the upper part of which the ure- thra opens, while below are the openings of the Wolffian (ejaculatory) ducts in the male or the orifice of the vagina in the female. From the sides of the lower part of the sinus a pair of evaginations arise toward the end of the fourth month and give rise to the glands of Bartholin of the female or the corresponding Cowper's glands in the male. The Development of the External Genitalia. — At about the fifth week, before the urogenital sinus has opened to the exterior, the mesenchyme on its ventral wall begins to thicken, producing a slight projection to the exterior. This eminence, which is known as the genital tubercle (Fig. 206, gt), rapidly increases in size, its extremity becomes some- what bulbously enlarged (Fig. 208, gl) and a groove, ex- tending to the base of the terminal enlargement, appears upon its vestibular surface, the lips of the groove forming two well-marked genital folds (Fig. 208, gf). At about the THE EXTERNAL GENITALIA. 385 tenth week there appears on either side of the tubercle an enlargement termed the genital swelling (Fig. 208, gs), which is due to a thickening of the mesenchyme of the lower part of the ventral abdominal wall in the region where the inguinal ligament is attached, and with the ap- pearance of these structures the indifferent stage of the external genitals is completed. In the female the growth of the genital tubercle pro- ceeds rather slowly and it becomes transformed into the clitoris, the genital folds becoming prolonged to form the Fig. 208. — The External Genitalia op an Embryo of 25 mm. a, Anus; g/, genital fold; gZ, glans; gs, genital swelling; p, perineal body. —(Keibel.) labia minora. The genital swellings increase in size, their mesenchyme becomes transformed into a mass of adipose and fibrous tissue and they become converted into the labia majora, the interval between them constituting the vulva. In the male the early stages of development are closely similar to those of the female; indeed, it has been well said that the external genitals of the adult female resemble those of the fetal male. In early stages the genital tuber- cle elongates to form the penis and the integument which covers the proximal part of it grows forward as a fold 386 THE DEVELOPMENT OF THE HUMAN BODY. which encloses the bulbous enlargement or glans and forms the prepuce, whose epithelium fuses with that cover- ing the glans and only separates from it later by a cornifi- cation of the cells along the plane of fusion. The genital folds meet together and fuse, converting the vestibule and the groove upon the vestibular surface of the penis into the terminal portion of the male urethra and bring- ing it about that the vasa deferentia and the uterus masculinus open upon the floor of that passage. The two genital swellings are at the same time brought closer together, so as to lie between the base of the penis and the perineal body and, eventually, they unite together to form the scrotum, the line of their junction being indi- cated by the median raphe. The mesenchyme of which they were primarily composed differentiates into the same layers as are found in the wall of the abdomen and a peri- toneal pouch is prolonged into them from the abdomen, so that they form sacs into which the testes descend to- ward the close of fetal life (see p. 388). The homologies of the portions of the reproductive apparatus derived from the cloaca and of the external genitalia in the two sexes may be perceived from the following table: Male. Female. Urinary bladder. Urinary bladder. Proximal portion of ure- Urethra. thra. Cowper's glands. Glands of Bartholin. Urogenital sinus, . . . The rest of the urethra. Vestibule. Genital tubercle, . . . Penis. Clitoris. Prepuce. Labia minora. Genital swellings, . . . Scrotum. Labia majora. It is stated above that the layers which compose the walls of THE DESCENT OF THE OVARIES. 387 the scrotum are identical with those of the abdominal wall. This may be seen in detail from the following scheme: Abdominal Walls. Scrotum. Integument. Integument. Superficial fascia Dartos. External oblique muscle. Intercolumnar fascia. Internal oblique muscle. Cremasteric fascia. Transversalis muscle. Infundibuliform fascia. Peritoneum. Tunica vaginalis. Numerous anomalies, depending upon an inhibition or excess of the development of the parts, may occur in connection with the external genitalia. Should, for instance, the lips of the groove on the vestibular surface of the penis fail to fuse, the penial portion of the urethra remains incomplete, constituting a condition known as hypospadias, a condition which offers a serious bar to the fulfilment of the sexual act. If the hypo- spadias is complete and there be at the same time an imperfect development of the penis, as frequently occurs in such cases, the male genitalia closely, resemble those of the female and a condition is produced which is usually known as hermaphrodit- ism. It is noteworthy that in such cases there is frequently a somewhat excessive development of the uterus masculinus, and a similar condition may be produced in the female by an ex- cessive development of the clitoris. Such cases, however, which concern only the accessory organs of reproduction, are instances of what is more properly termed spurious hermaphro- ditism, true hermaphroditism being a term which should be re- served for possible cases in which the genital ridges give rise in the same individual to both ova and spermatozoa. Such cases are of exceeding rarity in the human species, although occa- sionally observed in the lower vertebrates, and the great major- ity of the examples of hermaphroditism hitherto observed are cases of the spurious variety. The Descent of the Ovaries and Testes. — The positions finally occupied by the ovaries and testes are very differ- ent from those which they possess in the earlier stages of development, and this is especially true in the case of the testes. The change of position is partly due to the rate of growth of the inguinal ligaments being less than that 388 THE DEVELOPMENT OF THE HUMAN BODY. of the abdominal walls, the reproductive organs being thereby drawn downward toward the inguinal regions where the ligaments are attached. The attachment is to the bottom of a slight pouch of peritoneum which projects a short distance into the substance of the genital swellings and is known as the canal of Nuck in the female, and in the male as the -vaginal process. In the female a second factor combines with that just mentioned. The relative shortening of the inguinal liga- ments acting alone would draw the ovaries toward the inguinal regions, but the fusion of the lower ends of the Mullerian ducts, since the inguinal ligaments are united with these (see p. 371), produces a traction toward the median line, so that the organs come to lie finally in the true pelvis. With the testes the case is more complicated, since in addition to the relative shortening of the inguinal liga- ments, there is an elongation of the vaginal processes into the substance of the genital swellings. Three stages may be recognized in the descent of the testes. The first of these depends on the slow rate of elongation of the ingui- nal ligaments or gubernaculum. It lasts until about the fifth month of development, when the testes lie in the in- guinal region of the abdomen, but during this month the elongation of the gubernaculum becomes more rapid and brings about the second stage, during which there is a slight ascent of the testes, so that they come to lie a little higher in the abdomen. This stage is, however, of short duration, and is succeeded by the stage of the final de- scent, which is characterized by the elongation of the vagi- nal processes of the peritoneum into the substance of the scrotum (Fig. 209, A). Since the gubernaculum is at- tached to the bottom of the process, and since its growth has again diminished, the testes gradually assume again THE DESCENT OF THE TESTES. 389 their inguinal position, and are finally drawn down into the scrotum, slipping down between the walls of the vagi- nal processes and the infundibuliform fascia, which, to- gether with the other layers composing the scrotal wall, are differentiated at about this time. The condition which is thus acquired persists for some time after birth, the testicles being readily pushed up- ward into the abdominal cavity along the cavity by which they descended. Later, however, the size of the openings Fig. 209. — Diagrams Illustrating the Descent op the Testis. il, Inguinal ligament; m, muscular layer; s, skin and dartos of the scro- tum; t, testis; tv, tunica vaginalis; vd, vas deferens; vp, vaginal pro- cess of peritoneum. — {After Hertwig.) of the vaginal processes into the general peritoneal cavity becomes greatly reduced, so that each process becomes converted into an upper narrow neck and a lower sac-like cavity (Fig. 209, B), and, still later, the walls of the neck portion fuse and become converted into a solid cord, while the lower portion, wrapping itself around the testis, be- comes the tunica vaginalis (tv). By these changes the testes become permanently located in the scrotum. Dur- ing their descent the testes are drawn downward out of the mesenteries, the mesorchia, in which they were origi- 390 THE DEVELOPMENT OF THE HUMAN BODY. nally enclosed, and these structures flatten out and dis- appear, and, since the remains of each Wolffian body, the epididymis, and the upper part of each vas deferens, to- gether with the spermatic vessels and nerves, are drawn down into the scrotum with each testis, the mesenterial fold comparable to the broad ligament of the female also practically disappears, becoming converted into a sheath of connective tissue which encloses the vas deferens and the vessels and nerves, binding them together into what is termed the spermatic cord. In the text-books of anatomy the spermatic cord is usually described as lying in an inguinal canal which traverses the abdominal walls obliquely immediately above Poupart's liga- ment. So long as the lumen of the neck portion of the vaginal process of peritoneum remains patent there is such a canal, placing the cavity of the tunica vaginalis in communication with the general peritoneal cavity, but the cord does not traverse this canal but lies outside it in the retroperitoneal connective tissue. When, however, the neck of the vaginal process disap- pears, a canal no longer exists, although the connective tissue which surrounds the spermatic cord and unites it with the tissues of the abdominal walls is less dense than the neighboring tissues, so that the cord may readily be separated from these and thus appear to lie in a canal. The Development of the Suprarenal Bodies. — The supra- renal bodies make their appearance at an early stage, while the Wolffian bodies are still in a well-developed con- dition, and they are situated at first to the medial side of the upper ends of these structures (Fig. 197, sr). Their final relation to the metanephros is a secondary event, and in merely a topographic relation, there being no develop- mental relation between the two structures. Their development has been very variously described. In the Mammalia they arise by the proliferation of cells situated at the extremities of invaginations of the coelomic epithelium into the Wolffian ridge (Fig. 210), the groups THE SUPRARENAL BODIES. 39 1 of cells so formed from the several invaginations later unit- ing together to form a relatively large organ. The invagi- nations resemble closely in appearance and position the tubules and funnels of the pronephros (see p. 361), and they have recently (Aichel) been regarded as representing funnels belonging to the mesonephros. One of the char- acteristics of the mammalian mesonephros is that it pos- sesses no nephrostomes, but in the lower vertebrates such structures do occur, and it is possible that the invagina- tions of the coelomic epithelium which give rise to the suprarenals may be representatives of certain meso- wc «**».>*.> ^sm* l\ J =.--=.**. ss*5*X7\ Jo Fig. 210. — Section through a Portion op the Wolffian Ridge of a Rabbit Embryo of 6.5 mm. Ao, Aorta; ns, nephrostome ; Sr, suprarenal body; vc, cardinal vein; wc, tubule of Wolffian body; ied, Wolffian duct. — {Aichel.) nephric funnels which have failed to unite with the tu- bules and have undergone a secondary transformation. That the suprarenals are primarily connected with the mesonephros becomes exceedingly probable from the fact that similar structures, known as the accessory suprarenals of Marchand, not infrequently occur between the layers of the broad ligament of the female and in the vicinity of the epididymis in the male and are developed from the degenerating tubules of the epoophoron or paroophoron, and presumably from the corresponding structures in the male. 39 2 THE DEVELOPMENT OF THE HUMAN BODY. It is doubtful, however, if the entire mass of the supra- renal organs is derived from the constituents furnished by the mesonephros, although this is the view maintained by the most recent investigator of the subject (Aichel). In the fully formed organs a clear distinction obtains between the cortical and medullary portions, and earlier observers very generally maintained that the latter was derived from cells which separated from the neighboring ganglia of the sympathetic nervous system. Strong support is afforded to this view by the close connections which exist between the organs and the sympathetic nervous system in the adult condition, and also by the fact that the cells of the medullary substance possess a strong affinity for chromium salts, assuming a distinctly brown color when treated with solutions of these salts. The same chrom- affine nature is characteristic of the cells of certain other organs, such as the intercarotid . ganglia and Zucker- kandl's organs (see p. 450), whose origin from the sym- pathetic system seems to be beyond question. It is probable, therefore, that the suprarenal organs are formed by a combination of two constituents, one of which, derived from the mesonephros, forms the cortical portion of the organs, while the other, having its origin from the sympathetic ganglia, gives rise to the medullary portion. The mesenchyme in the vicinity of each organ condenses around it to form a capsule, and the organs in later stages receive a rich blood-supply. LITERATURE. O. Aichel: " Vergleichende Entwickelungsgeschichte und Stammesge- schichte der Nebennieren," Archiv fur mikrosk. Anat., lvi, 1900. O. FrAnkl: "Beitrage zur Lehre vom Descensus testiculorum," Sitzungs- ber. des kais. Akad. Wissensch. Wien, Math.-Naturwiss. Classe, ox, 1900 LITERATURE. 393 J. B. Haycraft: "The Development of the Kidney in the Rabbit," Inter- nal Monatsschrijt fur Anat. und Physiol., xii, 1898. J. Janosik: "Histologisch-embryologische Untersuchungen uber das Urogenitalsystem, "Sitzungsber. der kais. Akad. Wissensch. Wien, Math.-Naturwiss. Classe, xci, 1887. F. Keibel: "Zur Entwickelungsgeschichte des menschlichen Urogenital- apparatus," Archiv fur Anat. und Physiol., Anat. Abth., 1896. J. B. Macallum: "Notes on the Wolffian Body of Higher Mammals," Amer. Journ. of Anat., I. 1902. E. Martin: "Ueber die Anlage der Urniere beim Kaninchen," Archiv. fur Anat. und Physiol., Anat. Abth., 1888. H. Meyer: "Die Entwickelung der Urnieren beim Menschen," Archiv. fur mikrosk. Anat., xxxvi, 1890. G. von Mihalkovicz: "Untersuchungen fiber die Entwickelung des Harn- und Geschlechtsapparates der Amnioten," Internal. Monatsschrift fur Anat. und Physiol., n, 1885. W. Nagel: "Ueber die Entwickelung des Urogenitalsystems des Mensch- en," Archiv fur mikrosk. Anat., xxxiv, 1889. W. Nagel: "Ueber die Entwickelung des Uterus und der Vagina beim Menschen," Archiv fur mikrosk. Anat., xxxvn, 1891. W. Nagel: "Ueber die Entwickelung der innere und aussere Genitalien beim menschlichen Weiber," Archiv fur Gynakol., xlv, 1894. G. Pallin: "Beitrage zur Anatomie der Prostata und der Samenblasen," Archiv fur Anat. und Physiol., Anat. Abth., 1901. A. Soulie: "Sur la migration des Testicules," Comptes Rendus de la Soc de Biol. Paris, Ser lOme, n, 1895. A. Soulier " Sur le mecanisme de la migration des testicules," Comptes Rendus de la Soc. de Biol. Paris, Ser lOme, II, 1895. F. TournEux: "Sur le developpement et revolution du tubercule genital chez le fcetus humain dans les deux sexes," Journ. de I' Anat. et de la Physiol., xxv, 1889. S. Weber: "Zur Entwickelungsgeschichte des uropoetischen Apparates bei Saugern, mit besonderer Berficksichtigung der Urniere zur Zeit des Auftretens der bleibenden Mere," Morphol. Arbeiten, vii, 1897. P. WendElER: "Die fotale Entwickelung der menschlichen Tuben," Ar- chiv. fur mikrosk. Anat., xlv, 1895. H. von Winiwarter: "Recherches sur l'ovogenese et l'organogenese de l'ovaire des Mammiferes" (Lapin et Homme), Archives de Biol., xvn, 1900. 33 CHAPTER XIV. THE DEVELOPMENT OF THE NERVOUS SYSTEM. The Histogenesis of the Nervous System. — The entire central nervous system is derived from the cells lining the medullary groove, whose formation and conversion into the medullary canal has already been described (p. 1 14). When the groove is first formed, the cells lining it are somewhat more columnar in shape than those on either side of it, though like them they are arranged in a single layer; later they increase by mitotic division and arrange themselves in several layers, so that the ectoderm of the groove becomes very much thicker than that of the gene- ral surface of the body. While its tissue is in this condi- tion the lips of the groove unite, and the subsequent differ- entiation of the canal so formed differs somewhat in different regions, although a fundamental plan may be recognized. This plan is most readily perceived in the region which becomes the spinal cord, and may be de- scribed as seen in that region. Throughout the earlier stages, the cells lining the inner wall of the medullary tube are found in active prolifera- tion, some of the cells so produced arranging themselves with their long axes at right angles to the central canal and extending throughout the entire thickness of the wall to form a supportive framework (Fig. 211), while others, whose destiny is for the most part not yet deter- minable, and which therefore may be termed indifferent cells, occur in the meshes of this framework. At this 394 THE HISTOGENESIS OF THE NERVOUS SYSTEM. 395 stage a transverse section of the medullary tube shows it to be composed of two well-defined zones, an inner one immediately surrounding the central canal and composed of the indifferent cells and the bodies of the supportive or ependymal cells, and an outer one consisting of the branched prolongations of the ependymal cells. This outer layer is termed the marginal -velum (Randschleier) (Fig. 211, mv). The indif- ferent cells now begin to wander outward to form a definite layer, termed the mantle layer, lying between the marginal velum and the bodies of the ependymal cells (Fig. 212), and when this layer has become well established the cells composing it begin to divide and to differen- tiate into (1) cells termed neuroblasts , destined to become nerve-cells, and (2) others which appear to be supportive in character and are termed neuroglia cells (Fig. 212, B). The latter are for the most part small and have their cell-bodies drawn out into very numerous and exceed- ingly slender processes, which ramify among the neuro- blasts, these, on the other hand, being larger and each Fig 2 1 1 . — Ependymal Cells from the Spinal Cord of an Embryo of 4.25 MM. mv, Marginal velum. — {His.) 396 THE DEVELOPMENT OF THE HUMAN BODY. early developing a single strong process which grows out into the marginal velum and is known as an axis- cylinder. At a later period the neuroblasts also give rise to other processes, termed dendrites, more slender and shorter than the axis-cylinders, branching repeatedly and, as a rule, not extending beyond the limits of the mantle layer. The axis-cylinder processes of the majority of the neuro- Fig. 212. — Diagrams showing the Development of the Mantle Layer in the Spinal Cord. The circles, indifferent cells ; circles with dots, neuroglia cells ; shaded cells, germinal cells; circles with cross, germinal cells in mitosis; black cells, nerve-cells. — (Schaper.) blasts on reaching the marginal velum bend upward or downward and, after traversing a greater or less length of the cord, re-enter the mantle layer and terminate by dividing into numerous short branches which come into relation with the dendrites of adjacent neuroblasts. The processes of certain cells situated in the ventral region of the mantle zone pass, however, directly through the THE HISTOGENESIS OF THE NERVOUS SYSTEM. 397 marginal velum out into the surrounding tissues and con- stitute the ventral nerve-roots (Fig. 215). The dorsal nerve-roots have a very different origin. In embryos of about 2.5 mm., in which the medullary canal is only partly closed (Fig. 42), the cells which lie along the line of transition between the lips of the groove and the general ectoderm form a distinct ridge readily recog- nized in sections and termed the neural ridge (Fig. 213, A). When the lips of the groove fuse together the cells of the crest unite to form a wedge-shaped mass, completing the closure of the canal (Fig. 213, B), and later proliferate so as to extend outward over the surface of the canal (Fig. 213, C). Since this proliferation is most active in the re- gions of the crest which correspond to the meso- dermic somites there is formed a series of cell masses, arranged seg- mentally and situated in the mesenchyme at the sides of the medullary canal (Fig. 200). These cell-masses rep- resent the posterior root ganglia, and certain of their con- stituent cells, which may also be termed neuroblasts, early assume a fusiform shape and send out a process from each extremity. One of these processes, the axis-cylinder, grows inward toward the medullary canal and penetrates Fig. 213. — Three Sections Through the Medullary Canal op an Em- bryo OP 2.5 mm. — {von Lenhossek.) 39§ THE DEVELOPMENT OF THE HUMAN BODY. its marginal velum, and, after a longer or shorter course in this zone, enters the mantle layer and comes into contact with the dendrites of some of the central neuroblasts. The other process extends peripherally and is to be regarded as an extremely elongated dendrite. The processes from the cells of each ganglion aggregate to form a nerve, that formed by the axis-cylinders being the posterior root of a spinal nerve, while that formed by the dendrites soon unites with the ventral nerve-root of the corresponding segment to form the main stem of a spinal nerve. Fig. 214. — Cells from the Gasserian Ganglion of a Guinea-pig Embryo. a, Bipolar cell; b and c, transitional stages to d, T-shaped cells. — {van Gchuchten.) There is thus a very important difference in the modes of development of the two nerve-roots, the axis-cylinders of the ventral roots arising from cells situated in the wall of the medullary canal and growing outward (centrifu- gally ) , while those of the dorsal root spring from cells situ- ated peripherally and grow inward (centripetally) toward the medullary canal. In the majority of the dorsal root ganglia the points of origin of the two processes of each bi- polar cell gradually approach one another and eventually THE HISTOGENESIS OF THE NERVOUS SYSTEM. 399 come to arise from a common stem, a process of the cell- body which thus assumes a characteristic T form. From what has been said it will be seen that each axis- cylinder is an outgrowth from a single neuroblast and is part of its cell-body, as are also the dendrites. Consequently there is strong embryological evidence in support of the neurone theory, which regards the entire nervous system as composed of sepa- rate units, each of which corresponds to a cell and is termed a neurone. Doubts have recently been thrown on the complete individuality of the neurones in the adult (Apathy, Bethe), but both from the embryological and physiological standpoints their primary distinction seems to be established. By the development of the axis-cylinders which occupy the meshes of the marginal velum, that zone increases in thickness and comes to consist principally of nerve-fibers, while the cell-bodies of the neurones of the cord are situ- ated in the mantle zone. No such definite distinction of color in the two zones as exists in the adult is, however, noticeable until a late period of development, the medul- lary sheaths, which give to the nerve-fibers their white appearance not beginning to appear until the fifth month and continuing to form from that time onward until after birth. The origin of the myelin which composes the medullary sheaths is as yet uncertain, although the more recent observations tend to show that it is picked out from the blood and deposited around the axis-cylinders in some manner not yet understood. Its appearance is of im- portance as being associated with the beginning of the functional activity of the nerve-fibers. Various theories have been advanced to account for the formation of the medullary sheaths. It has been held that the myelin is formed at the expense of the outermost portions of the axis-cylinders themselves (von Kolliker), and, on the other hand, it has been regarded as an excretion of the cells which compose the primitive sheaths surrounding the fibers (Ranvier), a theory which is, however, invalidated by the fact that myelin 400 THE DEVELOPMENT OF THE HUMAN BODY. is formed around the fibers of the central nervous system which possess no primitive sheaths. As stated above, the more recent observations (Wlassak) indicate its exogenous origin. It has been seen that the central canal is closed in the mid-dorsal line by a mass of cells derived from the neural crest. These cells do not take part in the formation of the mantle layer, but become completely converted into ependymal tissue, and the same is true of the cells situ- ated in the mid-ventral line of the canal. In these two regions, known as the roof-plate and floor-plate respec- tively, the wall of the canal has a characteristic structure and does not share to any great extent in the increase of thickness which distinguishes the other regions (Fig. 215). In the lateral walls of the canal there is also noticeable a differentiation into two regions, a dorsal one standing in relation to the ingrowing fibers from the dorsal root gan- glia and known as the dorsal zone, and a ventral one, the ventral zone, similarly related to the ventral nerve-roots. In different regions of the medullary tube these zones, as well as the roof- and floor-plates, undergo different de- grees of development, producing peculiarities which may now be considered. The Development of the Spinal Cord. — Even before the lips of the medullary groove have met a marked enlarge- ment of the anterior portion of the canal is noticeable, the region which will become the brain being thus distin- guished from the more posterior portion which will be converted into the spinal cord. When the formation of the mesodermic somites is completed, the spinal cord ter- minates at the level of the last somite, and in this* region still retains its connection with the ectoderm of the dorsal surface of the body ; but in that portion of the cord which is posterior to the first coccygeal segment the his- tological differentiation does not proceed beyond the stage THE SPINAL CORD. 4OI when the walls consist of several layers of similar cells; the formation of neuroblasts and nerve-roots ceasing with the segment named. After the fourth month the more differentiated portion elongates at a much slower rate than the surrounding tissues and so appears to recede up the spinal canal, until its termination is opposite the second lumbar vertebra. The less differentiated portion, which retains its connection with the ectoderm until about the fifth month, is, on the other hand, drawn out into a slender filament whose cells degenerate during the sixth month, except in its uppermost part, so that it comes to be represented throughout the greater part of its extent by a thin cord composed of pia mater. -This cord is the structure known in the adult as the filum terminate, and lies in the center of a leash of nerves occupying the lower part of the spinal canal and termed the cauda equina. The existence of the cauda is due to the recession of the cord which necessitates for the lower lumbar, sacral and coccygeal nerves, a descent through the spinal canal for a greater or less distance, before they can reach the inter- vertebral foramina through which they make their exit. In the early stages of development the central canal of the cord is quite large and of an elongated oval form, but later it becomes somewhat rhomboidal in shape (Fig. 215, A), the lateral angles marking the boundaries between the dorsal and ventral zones. As development proceeds the sides of the canal in the dorsal region gradually approach one another and eventually fuse, so that this portion of the canal becomes obliterated (Fig. 215, B) and is indi- cated by the dorsal longitudinal fissure in the adult cord, the central canal of which corresponds to the ventral por- tion only of the embryonic cavity. While this process has been going on both the roof- and the floor-plate have be- come depressed below the level of the general surface of 34 4o: THE DEVELOPMENT OF THE HUMAN BODY. the cord,, and by a continuance of the depression of the floor-plate — a process really due to the enlargement and consequent bulging of the ventral zone — the ventral fis- sure is produced, the difference between its shape and that of the dorsal fissure being due to the difference in its development. Fig. 215. — Transverse Sections through the Spinal Cords op Em- bryos of (.4) about Four and a Haep Weeks and (B) about Three Months. cB, Column of Burdach; cG, column of Goll; dh, dorsal horn; dz, dorsal zone; fp, floor-plate; ob, oval bundle; rp, roof -plate; vk, ventral horn; vz, ventral zone. — (His.) The development of the mantle layer proceeds at first more rapidly in the ventral zone than in the dorsal, so that at an early stage (Fig. 215, A) the anterior horn of gray matter is much more pronounced, but on the development of the dorsal nerve-roots the formation of neuroblasts in the dorsal zone proceeds apace, resulting in the formation THE SPINAL CORD. 403 of a dorsal horn. A small portion of the zone, situated between the point of entrance of the dorsal nerve-roots and the roof-plate, fails, however, to give rise to neuro- blasts and is entirely converted into ependyma. This represents the future column of Goll (Fig. 4s©, A, cG), and at the point of entrance of the dorsal roots into the cord a well-marked oval bundle of fibers is formed (Fig. 215, A, ob) which, as development proceeds, creeps dor- sally over the surface of the dorsal horn until it meets the lateral surface of the column of Goll, and, its further pro- gress toward the median line being thus impeded, it in- sinuates itself between that column and the posterior horn to form the column of Burdach (Fig. 215, B, cB). Nothing definite is as yet known concerning the development of the other columns which are recognizable in the adult cord, but, from what is known of the adult anatomy, it seems certain that the crossed and pyramidal tracts are composed of fibers which grow downward in the meshes of the marginal velum from neuroblasts situated in the cerebral cortex, while the direct cerebellar tract and the fibers of the ground-bundles have their origin from cells of the mantle layer of the cord. The myelination of the fibers of the spinal cord begins be- tween the fifth and sixth months and appears first in the col- umns of Burdach, and about a month later in the columns of Goll. The myelination of the great motor paths, the crossed and direct pyramidal tracts, is the last to develop, appearing toward the end of the ninth month of fetal life. The Development of the Brain. — The enlargement of the anterior portion of the medullary canal does not take place quite uniformly, but is less along two transverse lines than elsewhere, so that the brain region early becomes divided into three primary vesicles which undergo further differen- tiation as follows. Upon each side of the anterior vesicle an evagination appears and becomes converted into a club-shaped structure attached to the ventral portion of the vesicle by a pedicle. These evaginations (Fig. 216, 404 THE DEVELOPMENT OF THE HUMAN BODY. my op) are known as the optic evaginations, and being con- cerned in the formation of the eye will be considered in the succeeding chapter. After their formation the antero- lateral portions of the vesicle become bulged out into two protuberances (h) which rap- idly increase in size and give rise eventually to the two cerebral hemispheres, which form, together with the por- tion of the vesicle which lies between them, what is termed the telencephalon or fore-brain, the remainder of the vesicle giving rise to what is known as the diencephalon (thalamencephalon) or 'tween- brain (Fig. 216, t). The mid- dle vesicle is bodily converted into the mesencephalon or mid- brain (m), but the posterior vesicle differentiates so that three parts may be recog- nized: (1) a rather narrow portion which immediately succeeds the mid-brain and is termed the isthmus (»'); (2) a portion whose roof and floor give rise to the cerebel- lum and pons respectively, and which is termed the metencephalon or hind-brain imt) ; and (3) a terminal portion which is known as the medulla oblongata, or, to retain a consistent nomenclature, the myelencephalon or after-brain (my). From each of these six divisions definite structures arise whose relations to Fig. 216. — Reconstruction of the Brain of an Embryo of 2.15 MM. h, Hemisphere; i, isthmus; m, mesencephalon ; mf, mid-brain flexure ; mi, metencephalon ; my, myelencephalon; nf, neck flexure ; ot, otic capsule ; op, optic evagination; t, thala- mencephalon. — (His.) THE BRAIN. 405 the secondary divisions and to the primary vesicles may be understood from the following table and from the annexed figure (Fig. 217), which represents a median lon- gitudinal section of the brain of a fetus of three months. /Myelencephalon Medulla oblongata (I). 1st Vesicle, . . . . j Metencephalon J Pons (II 1). (Cerebellum (II 2). Superior peduncles of the Isthmus ( cerebellum (III). (Crura cerebri (posterior por- tion). i-Crura cerebri (anterior por- 2d Vesicle Mesencephalon j tion) (IV 1). <- Corpora quadrigemina (IV 2) . r Pars mammillaria(V 1). Diencephalon i Optic thalamus (V 2). I Epiphysis (V 3). 3d Vesicle, .....) / T nfundibu i um (V I l). ' Telencephalon ^pus St * at " m < V * 2) ' F 1 Olfactory bulb (Vi 3) . I Hemispheres (VI 4). But while the walls of the primary vesicles undergo this complex differentiation, their cavities retain much more perfectly their original relations, only that of the first vesicle sharing to any great extent the modifications of the walls. The cavity of the third vesicle persists in the adult as the fourth ventricle, traversing all the subdivisions of the vesicle ; that of the second, increasing but little in height and breadth, constitutes the iter; while that of the first vesicle is continued into the cerebral hemispheres to form the lateral ventricles, the remainder of it constituting the third ventricle, which includes the cavity of the median portion of the telencephalon as well as the entire cavity of the diencephalon. 406 THE DEVELOPMENT OF THE HUMAN BODY. During the differentiation of the various divisions of the brain certain flexures appear in the roof and floor, and to a certain extent correspond with those already de- scribed as occurring in the embryo. The first of these flexures to appear occurs in the region of the mid-brain, the first vesicle being bent ventrally until it comes to lie at practically a right angle with the axis of the mid-brain. This may be termed the mid-brain flexure (Fig. 216, mj) Fig. 217- -Mediax Longitudinal Section of the Brain of an Embryo of the Third Month. — (His.) and corresponds with the head-bend of the embryo. The second flexure occurs in the region of the medulla oblon- gata and is known as the neck flexure (Fig. 216, nf); it corresponds with the similarly named bend of the embryo and is produced by a bending ventrally of the entire head, so that the axis of the mid-brain comes to lie almost at right angles with that of the medulla and that of the first vesicle parallel with it. Finally, a third flexure occurs in the region of the metencephalon and is entirely peculiar THE MYELENCEPHALON. 407 to the nervous system; it consists of a bending ventrally of the floor of the hind-brain, the roof of this portion of the brain not being affected by it, and it may consequently be known as the pons flexure. In the later development the pons flexure practically disappears, owing to the development in this region of the transverse fibers and nuclei of the pons, but the mid- brain and neck flexures persist, though greatly reduced in acuteness, the axis of the anterior portion of the adult brain being inclined to that of the medulla at an angle of about 134 degrees. The Development of the Myelencephalon. — In its poste- rior portion the myelencephalon closely resembles the spinal cord and has a very similar development. More anteriorly, however, the roof -plate (Fig. 218, rp) widens to form an exceedingly thin membrane, the posterior velum; with the broadening of the roof -plate there is as- sociated a broadening of the dorsal portion of the brain cavity, the dorsal and ventral zones bending outward, until, in the anterior portion of the after-brain, the mar- gins of the dorsal zone have a lateral position, and are, in- deed, bent ventrally to form a reflected lip (Fig. 218). The portion of the fourth ventricle contained in this division of the brain becomes thus converted into a broad shallow cavity, whose floor is formed by the ventral zones sepa- rated in the median line by a deep groove, the floor of which is the somewhat thickened floor-plate. About the fourth month there appears in the roof -plate a transverse groove into which the surrounding mesenchyme dips, and, as the groove deepens in later stages, the mesenchyme con- tinued within it becomes converted into blood-vessels, forming the chorioid plexus of the fourth ventricle, a structure which, as may be seen from its development, does not lie within the cavity of the ventricle, but is 4o8 THE DEVELOPMENT OF THE HUMAN BODY. separated from it by the portion of the roof -plate which forms the floor of the groove. In embryos of about 9 mm. the differentiation of the dorsal and ventral zones into ependymal and mantle layers is clearly visible (Fig. 218), and in the ventral zone the marginal velum is also well developed. Where the fibers from the sensory ganglion of the vagus nerve enter the dorsal zone an oval area (Fig. 218, fs) is to be seen which is evidently comparable to the oval bundle of the Fig. 218. — Transverse Section through the Medulla Oblongata of an Embryo of 9.1 mm. dz, Dorsal zone ; fp, floor-plate ; js, fasciculus solitarius ; /, lip ; rp. roof- plate ; vz, ventral zone ; X and XII, tenth and twelfth nerves. — {His.) cord and consequently with the column of Burdach. It gives rise to the solitary fasciculus of adult anatomy, and in embryos of 1 1 to 13 mm. it becomes covered in by the fusion of the reflected lip of the dorsal zone with the sides of the myelencephalon, this fusion, at the same time, drawing the margins of the roof-plate ventrally to form a secondary lip (Fig. 219). Soon after this a remarkable mi- gration ventrally of neuroblasts of the dorsal zone begins. Increasing rapidly in number the migrating cells pass on THE MYELENCEPHALON. 409 either side of the solitary fasciculus toward the territory of the ventral zone, and, passing ventrally to the ventral portion of the mantle layer, into which fibers have pene- trated and which becomes the formatio reticularis (Fig. 219, />•), they differentiate to form the olivary body (ol). The thickening of the floor-plate gives opportunity for fibers to pass across the median line from one side to the other, and this opportunity is taken advantage of at an early stage by the axis-cylinders of the neuroblasts of the Fig. 219. — Transverse Section through the Medulla Oblongata op an Embryo of about Eight Weeks. av, Ascending root of the trigeminus ; [r, reticular formation ; ol, olivary body; sf, solitary fasciculus; tr, restiform body; XII, hypoglossal nerve. — (His.) ventral zone, and later, on the establishment of the olivary bodies, other fibers, descending from the cerebellum, de- cussate in this region to pass to the olivary body of the opposite side. In the lower part of the medulla fibers from the neuroblasts of the nuclei of Goll and Burdach, which seem to be developments from the mantle layer of the dorsal zone, also decussate in the substance of the floor-plate ; these fibers, known as the arcuate fibers, pass in part to the cerebellum, associating themselves with fibers ascending from the spinal cord and with the olivary fibers 4-IO THE DEVELOPMENT OF THE HUMAN BODY. to form a round bundle situated in the dorsal portion of the marginal velum and known as the restiform body (Fig. 219, tr). The principal differentiations of the zones of the myelen- cephalon may be stated in tabular form as follows : Roof-plate, Posterior velum. / Nuclei of termination of sensory roots of \ cranial nerves. Dorsal zones, j Nuclei of Goll and Burdach. \ The olivary bodies. {Nuclei of origin of the motor roots of cranial nerves. The reticular formation. Floor-plate, The median raphe. The Development of the Metencephalon and Isthmus. — Our knowledge of the development of the metencephalon, isthmus, and mesencephalon is by no means as complete as is that of the myelencephalon. The pons develops as a thickening of the portion of the brain floor which forms the anterior wall of the pons flexure, and its transverse fibers are well developed by the fourth month (Mihal- kovicz), but all details regarding the origin of the pons nuclei are as yet wanting. If one may argue from what occurs in the myelencephalon, it seems probable that the reticular formation of the metencephalon is derived from the ventral zone, and that the median raphe represents the floor-plate. Furthermore, the relations of the pons nuclei to the reticular formation on the one hand, and its connection by means of the transverse pons fibers with the cerebellum on the other, suggest the possibility that they may be the metencephalic representatives of the olivary bodies and be formed by a migration ventrally of neuroblasts from the dorsal zones. The cerebellum is formed from the dorsal zones and roof-plate of the metencephalon and is a thickening of the THE METENCEPHALON. 411 tissue immediately anterior to the front edge of the poste- rior velum. This latter structure has in early stages a rhomboidal shape (Fig. 220, A) which causes the cere- bellar thickening to appear at first as if composed of two lateral portions inclined obliquely toward one another. In reality, however, the thickening extends entirely across the roof of the brain (Fig. 220, B), the roof -plate probably being invaded by cells from the dorsal zones and so giving rise to the vermis, while the lobes are formed directly from the dorsal zones. During the second month a groove appears on the ventral surface of each lobe, Fig. 220. — A, Dorsal View op the Brain of a Rabbit Embryo of 16 mm. ; B, Median Longitudinal Section of a Calf Embryo of 3 cm. c, Cerebellum; m, mid-brain. — {Mihalkovicz.) marking out an area which becomes the flocculus, and later, during the third month, transverse furrows appear upon the vermis dividing it into five lobes, and later still extend out upon the lobes and increase in number to pro- duce the lamellate structure characteristic of the cere- bellum. The histogenetic development of the cerebellum at first proceeds along the lines which have already been de- scribed as typical, but after the development of the man- tle layer the cells lining the greater portion of the cavity of the ventricle cease to multiply, only those which are 412 THE DEVELOPMENT OF THE HUMAN BODY. situated in the roof-plate of the metencephalon and along the line of junction of the cerebellar thickening with the roof-plate continuing to divide. The indifferent cells formed in these regions migrate outward from the median line and forward in the marginal velum to form a super- ficial layer, known as the epithelioid layer, and cover the entire surface of the cerebellum. The cells of this layer, like those of the man- tle, differentiate into neuroglia cells and neuroblasts, the latter for the most part mi- grating centrally at a later stage to mingle with the cells of the mantle layer and to become transformed into the granular cells of the cerebellar cor- tex. The neuroglia cells remain at the sur- face, however, forming the principal constitu- ent of the outer or, as it is now termed, the molecular layer of the cortex, and into this the dendrites of the Purkinje cells, probably derived from the mantle layer, project. The migration of the neuroblasts of the epithe- lial layer is probably completed before birth, at which time but few remain in the molecular layer to form the stellate cells of the adult. The origin of the dentate and other nu- clei of the cerebellum is at present unknown, but it seems probable that they arise from cells of the mantle layer. The nerve-fibers which form the medullary substance of Fig. 221. — Diagram Representing the Differentiation of the Cerebellar Cells. The circles, indifferent cells; circles with dots, neuroglia cells ; shaded cells, ger- minal cells; circles with cross, germinal cells in mitosis ; black cells, nerve-cells. L, Lateral recess ; M, median furrow, and R, floor of IV, fourth ventricle. — (Schaper.) THE ISTHMUS. 413 the cerebellum do not make their appearance until about the sixth month, when they are to be found in the ependymal tissue on the inner surface of the layer of gran- ular cells. Those which are not commissural or associa- tive in function converge to the line of junction of the cerebellum with the pons, and there pass into the mar- ginal velum of the pons, myelencephalon, or isthmus as the case may be. The dorsal surface of the isthmus is at first barely dis- tinguishable from the cerebellum, but as development pro- ceeds its roof-plate undergoes changes similar to those occurring in the medulla oblongata and becomes converted into the anterior velum and valve of Vieussens. In the dorsal portion of its marginal velum fibers passing to and from the cerebellum appear and form the superior pedun- cle of the cerebellum (brachium conjunctivum) , while ven- trally fibers, descending from the more anterior portions of the brain, form the crura cerebri. Nothing is at present known as to the history of the gray matter of this division of the brain, although it may be presumed that its ventral zones take part in the formation of the tegmentum, while from its dorsal zones the nuclei of the brachia conjunctiva are possibly derived. The following table gives the origin of the principal structures of the metencephalon and isthmus : , . r Posterior velum. Anterior velum. ' \ Vermis of cerebellum. Valve of Vieussens. Lobes of cerebellum. Brachia conjunctiva Flocculi. Dorsal zones ) Nuclei of termination of sensory roots of cranial nerves. Pons nuclei. r Nuclei of origin of motor Posterior part of crura Ventral zones, J roots of cranial nerves. cerebri. ] Reticular formation. Posterior part of teg- (^ mentum. Floor-plate, Median raphe. Median raphe. 414 THE DEVELOPMENT OF THE HUMAN BODY. The Development of the Mesencephalon. — Our knowledge of the development of this portion of the brain is again very imperfect. During the stages when the flexures of the brain are well marked (Figs. 216 and 217) it forms a very prominent structure and possesses for a time a capa- cious cavity. Later, however, it increases in size less rapidly than adjacent parts and its walls thicken, the roof- and floor-plates as well as the zones, and, as a result, the cavity becomes the relatively smaller canal-like iter. In the marginal velum of its ventral zone fibers appear at about the third month, forming the anterior portion of the crura cerebri, and, at the same time, a median longitudi- nal furrow appears upon the dorsal surface, dividing it into two lateral elevations which, in the fifth month, are di- vided transversely by a second furrow and are thus con- verted from corpora bigemina (in which form they are found in the lower vertebrates) into corpora quadrigemina. Nothing is known as to the differentiation of the gray matter of the dorsal and ventral zones of the mid-brain. From the relation of the parts in the adult it seems probable that in addi- tion to the nuclei of origin of the oculomotor and trochlear nerves, the ventral zones give origin to the gray matter of the tegmentum, which is the forward continuation of the reticular formation. Similarly it may be supposed that the corpora quad- rigemina are developments of the dorsal zones, as may also be the red nuclei, whose relations to the superior peduncles of the cerebellum suggest a comparison with the olivary bodies and the nuclei of the pons. A tentative scheme representing the origin of the mid-brain structures may be stated thus : Roof-plate, (?) ( Corpora quadrigemina. Dorsal zones \ Red nuc i e i. , Nuclei of origin of the third and fourth nerves. Ventral zones . ... | Anterior part of tegmentum. 1 Anterior part of crura cerebri. Floor-plate, Median raphe. THE DIENCEPHALON. 415 The Development of the Diencephalon. — A transverse section through the diencephalon of an embryo of about five weeks (Fig. 222) shows clearly the differentiation of this portion of the brain into the typical zones, the roof- plate (rp) being represented by a thin-walled, somewhat folded area, the floor-plate (fp) by the tissue forming the floor of a well-marked ventral groove, while each lateral wall is divided into a dorsal and ventral zone by a groove known as the sulcus Monroi (Sm), which extends forward and ventrally toward the point of origin of the optic evagination (Fig. 224). At the posterior end of the ridge- like elevation which repre- sents the roof-plate is a rounded elevation (Fig. 223, p) which, in later stages, elongates until it almost reaches the dermis, forming a hollow evagination of the brain roof known as the pineal process. The distal extremity of this process en- larges to a sac-like structure which later becomes lobed, and, by an active proliferation of the cells lining the cavi- ties of the various lobes, finally becomes a solid structure, the pineal body. The more proximal portion of the evag- ination, remaining hollow, forms the pineal stalk, and the entire structure, body and stalk, constitutes what is known as the epiphysis. The significance of this organ in the Mammalia is doubtful. In the Reptilia and other lower forms the outgrowth is double, Fig. 222.— Transverse Sec- tion OF THE THALAMENCEPH- alon of an Embryo of Five Weeks. dz, Dorsal zone ; fp, floor-plate ; rp, roof-plate ; Sm, sulcus Monroi ; vz, ventral zone. — (His.) 4l6 THE DEVELOPMENT OF THE HUMAN BODY. a secondary outgrowth arising from the base or from the anterior wall of the primary one. This anterior evagination elongates until it reaches the dorsal epidermis of the head, and, here expanding, develops into an unpaired eye, the epidermis which overlies it becoming converted into a transparent cornea. In the Mammalia this anterior process does not develop and the epiphysis in these forms is comparable only to the posterior pro- cess of the Reptilia. In addition to the epiphysial evaginations, another evagina- tion arises from the roof-plate of the first brain vesicle, further forward, in the region which becomes the median portion of the telencephalon. This paraphysis, as it has been called, has been observed in the lower vertebrates and in the Marsupials (Se- lenka), but up to the present has not been found in other groups of the Mammalia. It seems to be comparable to a chorioid plexus which is evaginated from the brain surface instead of being invaginated as is usually the case. There is no evidence that a paraphysis is developed in the human brain. The portion of the roof -plate which lies in front of the epiphysis represents the velum interpositum of the adult brain, and it forms at first a distinct ridge (Fig. 223). At an early stage, however, it becomes reduced to a thin membrane upon the surface of which blood-vessels, de- veloping in the surrounding mesenchyme, arrange them- selves at about the third month in two longitudinal plexuses, which, with the subjacent portions of the velum, become invaginated into the cavity of the third ventricle to form its chorioid plexus. The dorsal zones thicken in their more dorsal and ante- rior portions to form massive structures, the optic thalami (Figs. 217, /V2, and 223, ot), which, encroaching upon the cavity of the ventricle, transform it into a narrow slit-like space, so narrow, indeed, that at about the fifth month the inner surfaces of the two thalami come in contact in the median line, forming what is known as the middle or soft commissure. More veritrally and posteriorly another thickening of the dorsal zones occurs, giving rise on each THE DIENCEPHALON. 417 side to the pulvinar of the thalamus and to an external geniculate body, and two ridges extending backward and dorsally from the latter structures to the thicken- ings in the roof of the mid- brain which represent the anterior corpora quadri- gemina, give a path along which the nerve-fibers which constitute the ante- rior brachia pass. From the ventral' zones what is known as the sub- thalamic region develops, a mass of fibers and cells whose relations and devel- opment are not yet clearly understood, but which may be regarded as the forward continuation of the teg- mentum and reticular for- mation. In the median line of the floor of the ventricle an unpaired thickening ap- pears, representing the cor- pora albicantia, which dur- ing the third month be- comes divided by a median furrow into two rounded eminences; but whether these structures and the posterior portion of the tuber cinereum, which also de- velops from this region of the brain, are derivatives of the ventral zones or of the floor-plate is as yet uncertain. 35 Fig. 223. — Dorsal View of the Brain, the Roof op the Lat- eral Ventricles being Re- moved, of an Embryo of 13.6 MM. b, Anterior brachium ; eg, external geniculate body; cp, chorioid plexus; cqa, anterior corpus quadrigeminum ; /(, hippocam- pus ; hf, hippocampal fissure ; ot, optic thalamus; p, pineal body; rp, roof-plate. — (His.) 41 8 THE DEVELOPMENT OF THE HUMAN BODY. Assuming that the albicantia and the tuber cinereum are derived from the ventral zones, the origins of the structures formed from the walls of the diencephalon may be tabulated as follows : Roof-plate, J ™" m interpositum I Epiphysis. r Optic thalami. Dorsal zones, -j Pulvinares. y External geniculate bodies. {Subthalamic region. Corpora albicantia. Tuber cinereum (in part). Floor-plate, Tissue of mid-ventral line. The Development of the Telencephalon. — For convenience of description the telencephalon may be regarded as con- sisting of a median portion, which contains the anterior part of the third ventricle, and two lateral outgrowths which constitute the cerebral hemispheres. The roof of the median portion undergoes the same transformation as does the greater portion of that of the diencephalon and is converted into the anterior part of the velum inter- positum (Fig. 224, vi), which anteriorly passes into the anterior wall of the third ventricle, the lamina terminalis (It), a structure which is to be regarded as formed by the union of the dorsal zones of opposite sides, since it lies entirely dorsal to the anterior end of the sulcus Monroi. From the ventral part of the dorsal zones the optic evagi- nations are formed, a depression, the optic recess (or), marking their point of origin. The ventral zones are but feebly developed, and form the anterior part of the subthalamic region, while at the anterior extremity of the floor-plate an evagination oc- curs, the infundibular recess (ir), which elongates to form a funnel-shaped structure known as the hypophysis. At its extremity the hypophysis comes in contact during the fifth week with the enlarged extremity of Rathke's pouch THE TELENCEPHALON. 419 formed by an invagination of the roof of the oral sinus (see p. 300), and applies itself closely to the posterior sur- face of this (Fig. 217) to form with it the pituitary body. The anterior lobe at an early stage separates from the mucous membrane of the oral sinus, the stalk by which it was attached completely disappearing, and toward the end of the second month it begins to send out processes from its walls into the surrounding mesenchyme and so or ir Fig. 224.- -Median Longitudinal Section op the Brain of an Em- bryo op 13.6 MM. br, Anterior braehium; eg, corpus geniculatum externum; cs, corpus stria- tum; h, cerebral hemisphere; ir, infundibular recess; It, lamina term- inalis ; or, optic recess ; ot, optic thalamus ; p, pineal process ; sm, sul- cus Monroi; st, subthalamic region; to, velum interpositum. — (His.) becomes converted into a mass of solid epithelial cords embedded in a mesenchyme rich in blood and lymphatic vessels. The cords later on divide transversely to a greater or less extent to form alveoli, the entire structure coming to resemble somewhat the parathyreoid bodies (see p. 314), and, like these, having the function of pro- ducing an internal secretion. The posterior lobe, de- rived from the brain, retains its connection with that 420 . THE DEVELOPMENT OF THE HUMAN BODY. structure, its stalk being the infundibulum, but its ter- minal portion does not undergo such extensive modifica- tions as does the anterior lobe, although it is claimed that it gives rise to a glandular epithelium which may become arranged so as to form alveoli. The cerebral hemispheres are formed from the lateral portions of the dorsal zones, each possessing also a pro- longation of the roof-plate. From the more ventral por- tion of each dorsal zone there is formed a thickening, the corpus striatum (Figs. 224, cs, and 217, VI 2), a structure which is for the telencephalon what the optic thalamus is for the diencephalon, while from the more dorsal por- tion there is formed the remaining or mantle (pallial) por- tions of the hemispheres (Figs. 224, h, and 217, VI 4). When first formed, the hemispheres are slight evagina- tions from the median portion of the telencephalon, the openings by which their cavities communicate with the third ventricle, the foramina of Monro, being relatively very large (Fig. 224), but, in later stages (Fig. 217), they increase more markedly and eventually surpass all the other portions of the brain in magnitude, overlapping and completely concealing the roof and sides of the dienceph- alon and mesencephalon and also the anterior surface of the cerebellum. In this enlargement, however, the foramina of Monro share only to a slight extent, and con- sequently become relatively smaller (Fig. 217), forming in the adult merely slit-like openings lying between the lamina terminalis and the optic thalami and having for their roof the anterior portion of the velum interpositum. The velum interpositum, — that is to say, the roof -plate, — -where it forms the roof of the foramen of Monro, is prolonged out upon the dorsal surface of each hemisphere, and, becoming invaginated, forms upon it a groove. As the hemispheres, increasing in height, develop a mesial THE TELENCEPHALON. 421 wall, the groove, which is the so-called chorioidal fissure, comes to lie along the ventral edge of this wall, and as the growth of the hemispheres continues it becomes more and more elongated, being carried at first backward (Fig. 225), then ventrally, and finally forward to end at the tip of the temporal lobe. After the establishment of the grooves the mesenchyme in their vicinity dips into them, and, developing blood-vessels, becomes the chorioid plexuses of the lateral ventricles, and at first these plexuses grow much more rapidly than the ventricles, and so fill them al- most completely. Later, how- ever, the walls of the hemi- spheres gain the ascendancy in rapidity of growth and the plexuses become relatively much smaller. Since the portions of the roof-plate which form the chorioidal fissures are continu- ous with the velum interpositum in the roofs of the foramina of Monro, the chorioid plexuses of the lateral and third ventricles become continuous also at that point. The mode of growth of the chorioid fissures seems to indicate the mode of growth of the hemispheres. At first the growth is more or less equal in all directions, but later it becomes more extensive posteriorly, there being more room for expansion in that direction, and when further extension backward becomes difficult the posterior extremities of the hemispheres bend ventrally toward the base of the cranium, and, reaching this, turn forward to form the temporal lobes. As a result the cavities of the Fig. 225. — Median Longi- tudinal Section of the Brain of an Embryo Calf of 5 cm. cb, Cerebellum ; cp, chorioid plexus; cs, corpus stria- tum ; fM, foramen of Mon- ro ; in, hypophysis ; m, mid- brain; oc, optic commis- sure ; t, posterior part of the thalamencephalon. — (Mihalkovicz.) 422 THE DEVELOPMENT OF THE HUMAN BODY. hemispheres, the lateral ventricles, in addition to being carried forward to form an anterior horn, are also carried backward and ventrally to form the lateral or descending horn, and the corpus striatum likewise extends backward to the tip of each temporal lobe as a slender process known as the tail of the caudate nucleus. In addition to the anterior and lateral horns, the ventricles of the human brain also possess posterior horns extending backward into the occipital portions of the hemispheres, these por- tions, on account of the greater persistence of the mid- brain flexure (see p. 406), being enabled to develop to a greater extent than in the lower mammals. The scheme of the origin of parts in the telencephalon may be stated as follows : Roof-plate, . . Dorsal zones, Ventral zones, { Median Part. Anterior part of Velum interpositum. J Lamina terminalis. (. Optic evaginations. Hemispheres. i Floor of chorioidal fis- \ sure. ! Pallium. Corpus striatum. Olfactory bulbs (see p 427). Anterior part of sub- thalamic region. Anterior part of tuber cinereum. The Convolutions of the Hemispheres. — The growth of the hemispheres to form the voluminous structures found in the adult depends mainly upon an increase of size of the pallium. The corpus striatum, although it takes part in the elongation of each hemisphere, nevertheless does not increase in other directions as rapidly and extensively as the pallium, and hence, even in very early stages, a de- pression appears upon the surface of the hemispheres where the corpus is situated (Fig. 226). This depression is THE CEREBRAL CONVOLUTIONS. 423 the fossa Sylvii, and for a considerable period it is the only sign of inequality of growth on the outer surfaces of the hemispheres. Upon the mesial surfaces, however, at about the time that the chorioid fissure appears, another linear depression is formed dorsal to the chorioid, and when fully formed extends from in front of the foramen of Monro to the tip of the temporal lobe (Fig. 228, h). It affects the entire thickness of the pallial wall and conse- quently produces an elevation upon the inner surface, a projection into the cavity of the ventricle which is known as the hippocampus , whence the fissure may be termed the hippocampal fissure. The portion of the pallium which inter- venes between this fissure and the chori- oidal forms what is known as the dentate gyrus. Toward the end of the third or the be- ginning of the fourth month two prolonga- tions arise from the fissure just where it turns to be continued into the temporal lobe, and these, extending posteriorly, give rise to the parieto- occipital and calcarine fissures. Like the hippocampal, these fissures produce elevations upon the inner surface of the pallium, that formed by the parieto-occipital early disappearing, while that produced by the calcarine persists to form the calcar (kippocam.pus minor) of adult anatomy. The three fissures just described, together with the Fig. 226. — Brain of an Embryo of the Fourth Month. c, Cerebellum; />, pons; s, Sylvian fossa. 424 THE DEVELOPMENT OF THE HUMAN BODY. chorioidal and the fossa of Sylvius, are all formed by the beginning of the fourth month and all affect the entire thickness of the wall of the hemisphere, and hence have been termed the primary or total fissures. Until the begin- ning of the fifth month they are the only fissures present, but at that time secondary fissures, which, with one excep- tion, are merely furrows of the surface of the pallium, make their appearance and continue to form until birth and possibly later. Before considering these, however, certain changes which occur in the neighborhood of the Sylvian fossa may be described. The fossa is at first a triangular depression situated above the temporal lobe on the surface of the hemisphere. During the fourth month it deepens considerably, so that its upper and lower margins become more pronounced and form projecting folds, and, during the fifth month, these two folds approach one another and eventually cover in the floor of the fossa completely, the groove which marks the line of their contact forming the Sylvian fissure, while the floor of the fossa becomes known as the island of Reil {insula). The first of the secondary fissures to appear is the cal- loso-marginal, which is formed about the middle of the fifth month on the mesial surface of the hemispheres, lying parallel to the anterior portion of the hippocampus fissure and dividing the mesial surface into the gyri marginalis and fornicatus. A little later, at the beginning of the sixth month, several other fissures make their ap- pearance upon the outer surface of the pallium, the chief of these being the fissure of Rolando, the intra- parietal, the pre- and post-central, and the temporal fissures, the most ventral of these last running parallel with the lower portion of the hippocampal fissure and differing from the others in forming a ridge on the wall of the ventricle THE CORPUS CALLOSUM. 425 termed the collateral eminence, whence the fissure is known as the collateral. The position of most of these fissures may be seen from Fig. 227, and for a more com- plete description of them reference may be had to text- books of descriptive anatomy. In later stages numerous tertiary fissures make their appearance and mask more or less extensively the SeC- ^C Fig. 227. — Cerebral Hemisphere of an Embryo op about the Seventh Month. s, Superior frontal fissure; ip, intraparietal ; IR, island of Reil; pci, in- ferior pre-central; pes, superior pre-central; ptc, post- central ; R, Rolandic; S, Sylvian; t 1 , first temporal. — {Cunningham.) ondaries, than which they are, as a rule, much more incon- stant in position and shallower. The Corpus Callosum and Fornix. — While these fissures have been forming, important structures have developed in connection with the lamina terminalis. Up to about the fourth month the lamina is thin and of nearly uniform thickness throughout, but at this time it begins to thicken at its dorsal edge to form a mass which is triangular in 36 426 THE DEVELOPMENT OF THE HUMAN BODY. section and connects the mesial surfaces of the two hemi- spheres. The ventral angle of the thickening later sepa- rates slightly from the rest and fibers appear in it, con- verting it into the anterior commissure, and the remainder of the thickening, continuing to increase in size with the increase of the hemispheres, forms a mass of considerable size, still retaining its triangular shape and having its apex di- rected posteriorly. In the dorsal portion of the triangle fibers ex- tend across from the pallium of one hemi- sphere to that of the other and form the corpus callosum, while in its ventral edge other fibers extend from the hippocampus to the lamina termin- alis, and, descending in that structure, pass posteriorly in the floor of the third ventricle toward the corpora albicantia. These fi- bers constitute the pillars of the fornix, whose peculiar course in the adult brain may be understood by a con- sideration of the rotation of the hemispheres during growth which results in the formation of the temporal lobe (seep. 421). The portion of the triangle included between the callo- sum and the fornix remains thin and forms the septum Fig. 228. — Median Longitudinal Sec- tion of the Brain of an Embryo of Three Months. c, Calcarine fissure ; ca, anterior commis- sure ; cc, corpus callosum ; cf, chorioidal fissure; dg, dentate gyrus; fm, foramen of Monro ; h, hippocampal fissure ; po, parieto-occipital fissure. — ( Mikalko- vciz.) THE OLFACTORY LOBES. 427 lucidum, and a split occurring in the center of this gives rise to the so-called fifth ventricle, which, from its mode of formation, is a completely closed cavity and is not lined with ependymal tissue of the same nature as that found in the other ventricles. Owing to the very considerable size reached by the thickening of the lamina terminalis whose history has just been described, important changes are wrought in the adjoining portions of the mesial surface of ___J~_ dg the hemispheres. Be- fore the development of the thickening the gyrus dentatus and the hippocampus ex- tend forward into the anterior portion of the hemispheres (Fig. 228), but on account of their position they become encroached upon by the enlarge- ment of the lamina terminalis, with the result that the hippo- campus becomes practically obliterated in that portion- of its course which lies in the region occupied by the cor- pus callosum, its fissure in this region becoming known as the callosal fissure, while the corresponding portions of the dentate gyrus become reduced to narrow and in- significant bands of nerve-tissue which rest upon the upper surface of the corpus callosum and are known as the stria of Lancisi. The Olfactory Lobes. — At the time when the cerebral Fig. 229. — Median Longitudinal Sec- tion of the Brain of an Embryo of the Fifth Month. ac. Anterior commissure; cc, corpus cal- losum ; dg, dentate gyrus ; /, fornix ; i, infundibulum; mc, middle commis- sure; si, septum lucidum; vi, velum interpositum. — {Mihalkovicz.) 428 THE DEVELOPMENT OF THE HUMAN BODY. hemispheres begin to enlarge — that is to say, at about the fourth week — a slight furrow, which appears on the ven- tral surface of each anteriorly, marks off an area which, continuing to enlarge with the hemispheres, gradually becomes constricted off from them to form a distinct lobe-like structure, the olfactory lobe (Fig. 217, VI 3). In most of the lower mammalia these lobes reach a very considerable size, and consequently have been regarded as constituting an additional division of the brain, known as the rhinencephalon, but in man they remain smaller, and although they are at first hollow, containing pro- longations from the lateral ventricles, the cavities later on disappear and the lobes become solid. Each lobe becomes differentiated into two portions, its terminal por- tion becoming converted into the club-shaped structure, the olfactory bulb and stalk, while its proximal portion gives rise to the olfactory tracts, the trigone, and the anterior perforated space. Histogenesis of the Cerebral Cortex. — A satisfactory study of the histogenesis of the cortex has not yet been made. In embryos of three months a marginal velum is present and probably gives rise to the stratum zonale of the adult brain ; beneath this is a cellular layer, perhaps represent- ing the mantle layer; beneath this, again, a layer of nerve- fibers is beginning to appear, representing the white sub- stance of the pallium ; and, finally, lining the ventricle is an ependymal layer. In embryos of the fifth month toward the innermost part of the second layer cells are beginning to differentiate into the large pyramid cells, but almost nothing is known as to the origin of the other layers recognizable in the adult cortex, nor is it known whether any migration, similar to what occurs in the cere- bellar cortex, takes place. The fibers of the white sub- stance do not begin to acquire their myelin sheaths until THE SPINAL NERVES. 429 toward the end of the ninth month, and the process is not completed until some time after birth (Flechsig), while the fibers of the cortex continue to undergo myelination until comparatively late in life (Kaes) . The Development of the Spinal Nerves. — It has already been seen that there is a fundamental difference in the mode of development of the two roots of which the typical spinal nerves are composed, the ventral root being formed by axis-cylinders which arise from neuroblasts situated within the substance of the spinal cord, while the dorsal roots arise from the cells of the neural crests, their axis- cylinders growing into the substance of the cord while their dendrites become prolonged peripherally to form the sensory fibers of the nerves. Throughout the thoracic, lumbar and sacral regions of the cord the fibers which grow out from the anterior horn cells converge to form a single nerve-root in each segment, but in the cervical region the fibers which arise from the more laterally situ- ated neuroblasts make their exit from the cord inde- pendently of the more ventral neuroblasts and form the roots of the spinal accessory nerve (see p. 438). In the cervical region there are accordingly three sets of nerve- roots, the dorsal, lateral, and ventral sets, the last being not quite' equivalent to the similarly named roots of the more posterior nerves. In a typical spinal nerve, such as one of the thoracic series, the dorsal roots as they grow peripherally pass downward as well as outward, so that they quickly come into contact with the ventral roots with whose fibers they mingle, and the mixed nerve so formed soon after divides into two trunks, a dorsal one, which is distributed to the dorsal musculature and integument, and a larger ventral one. The ventral division as it continues its outward growth soon reaches the dorsal angle of the pleuro-peri- 430 THE DEVELOPMENT OF THE HUMAN BODY. toneal cavity, where it divides, one branch passing into the tissue of the body- wall while the other passes into the splanchnic mesoderm. The former branch, continuing its onward course in the body-wall; again divides, one branch becoming the lateral cutaneous nerve, while the other continues inward to terminate in the median ven- tral portion of the body as the anterior cutaneous nerve. The splanchnic branch forms a ramus communicans to the sympathetic system and will be considered more fully later on. The conditions just described are those which obtain throughout the greater part of the thoracic region. Else- where the fibers of the ventral divisions of the nerves as they grow outward tend to separate from one another and to become associated with the fibers of adjacent nerves, giving rise to plexuses. In the regions where the limbs occur the formation of the plexuses is also associated with a shifting of the parts to which the nerves are supplied, a factor in plexus formation which is, however, much more evident from comparative anatomical than from embry- logical studies. The Development of the Cranial Nerves. — During the last thirty years the cranial nerves have received a great deal of attention in connection with the idea that an accurate knowledge of their development would afford a clue to a most vexed problem of vertebrate morphology, the metamerism of the head. That the metamerism which was so pronounced should extend into the head was a natural supposition, strengthened by the discovery of head-cavities in the lower vertebrates and by the indica- tions of metamerism seen in the branchial arches, and the problem which presented itself was the correlation of the various structures belonging to each metamere and the determination of the modifications which they had under- gone during the evolution of the head. THE CRANIAL NERVES. 43 I In the trunk region a nerve forms a conspicuous ele- ment of each metamere and is composed, according to what is known as Bell's law, of a ventral or efferent and a dorsal or afferent root. Until comparatively recently the study of the cranial nerves has been dominated by the idea that it was possible to extend the application of Bell's law to them and to recognize in the cranial region a num- ber of nerve pairs serially homologous with the spinal nerves, some of them, however, having lost their afferent roots, while in others a dislocation, as it were, of the two roots had occurred. The results obtained from investigation along this line have not, however, proved entirely satisfactory, and facts have been elucidated which seem to show that it is not possible to extend Bell's law, in its original form at least, to the cranial nerves. It has been found that it is not sufficient to recognize simply afferent and efferent roots, but these must be analyzed into further components, and when this is done it is found that in the series of cranial nerves certain components occur which are not repre- sented in the nerves of the spinal series. Before proceeding to a description of these components it will be well to call attention to a matter already alluded to in a previous chapter (p. 127) in connection with the segmentation of the mesoderm of the head. It has been pointed out that while there exist "head-cavities" which are serially homologous with the mesodermal somites of the trunk, there has been imposed upon this primary cranial metamerism a secondary metamerism represented by the branchiomeres associated with the branchial arches, and, it may be added,'this secondary metamerism has become the more prominent of the two, the primary one, as it developed, gradually slipping into the back- ground until, in the higher vertebrates, it has become to 432 THE DEVELOPMENT OF THE HUMAN BODY. a very considerable extent rudimentary. In accordance with this double metamerism it is necessary to recognize two sets of cranial muscles, one derived from the cranial myotomes and represented by the muscles of the eyeball, and one derived from the branchiomeric mesoderm, and it is necessary also to recognize for these two sets of mus- cles two sets of motor nerves, so that, with the dorsal or Fig. 230. — Transverse Section through the Medulla Oblongata of an Embryo of 10 mm., showing the Nuclei of Origin of the Vagus (X) and Hypoglossal (XII) Nerves. — (His.) sensory nerve-roots,, there are altogether three sets of nerve-roots in the cranial region instead of only two, as in the spinal region. These three sets of roots are readily recognizable both in the embryonic and in the adult brain, especially if at- tention be directed to the cell groups or nuclei with which they are associated (Fig. 230). Thus there can be recog- THE CRANIAL NERVES. 433 nized : (i ) a series of nuclei from which nerve-fibers arise, situated in the floor of the fourth ventricle and iter close to the median line and termed the ventral motor nuclei; (2) a second series of nuclei of origin, situated more lat- erally and in the substance of the formatio reticularis, and known as the lateral motor nuclei; and (3) a series of nuclei in which afferent nerve-fibers terminate, situated still more laterally in the floor of the ventricle and forming the dorsal or sensory nuclei. None of the twelve cranial nerves usually recognized in the text-books contain fibers associated with all three of these nuclei; the fibers from the lateral motor nuclei almost invariably unite with sen- sory fibers to form a mixed nerve, but those from all the motor nuclei form independent roots, while the olfactory and auditory nerves alone, of all the sensory roots (omit- ting for the present the optic nerve), do not contain fibers from either of the series of motor nuclei. The relations of the various cranial nerves to the nuclei may be seen from the following table, in which the + sign indicates the presence and the — sign the absence of fibers from the nuclear series under which it stands : Ventral Lateral Number. Name. Motor. Motor. Sensory. I. Olfactory. — — + III. Oculomotor. + — — IV. Trochlear. + — — V. Trigeminus. + + VI. Abducens. + — — VII. Facial. + + VIII. Auditory. — ~r IX. Glossopharyngeal. — + + X. XI. Vagus. 1 Spinal Accessory. / — + + Two nerves — namely, the second and twelfth— have been omitted from the above table. Of these, the second or optic nerve undoubtedly belongs to an entirely differ- 434 TH E DEVELOPMENT OF THE HUMAN BODY. ent category from the other peripheral nerves, and will be considered in the following chapter in connection with the sense-organ with which it is associated (see especially p. 489). The twelfth or hypoglossal nerve, on the other hand, really belongs to the spinal series and has only sec- ondarily been taken up into the cranial region in the higher vertebrates. It has already been seen (p. 192 ) that the bodies of four vertebrae are included in the basioccipi- tal bone, and that three of the nerves corresponding to these vertebrae are represented in the adult by the hypo- glossal and the fourth by the first cervical or suboccipital nerve. The dorsal roots of the hypoglossal nerves seem to have almost disappeared, although a ganglion has been observed in embryos of 7 and 10 mm. in the posterior part of the hypoglossal region (His), and probably repre- sents the dorsal root of the most posterior portion of the hypoglossal nerve. This ganglion disappears, as a rule, in later stages, and it is interesting to note that the ganglion of the suboccipital nerve is also occasionally wanting in the adult condition. The hypoglossal roots are to be re- garded, then, as equivalent to the ventral roots of the cervical spinal nerves, and the nuclei from which they arise lie in series with the cranial ventral motor roots, a fact which indicates the equivalency of these latter with the fibers which arise from the neuroblasts of the anterior horns of the spinal cord. The equivalents of the lateral motor roots may more conveniently be considered later on, but it may be pointed out here that these are the fibers which are distributed to the muscles of the branchiomeres. In the case of the sensory nerves a further analysis is necessary before their equivalents in the spinal series can be determined. For this the studies which have been made in recent years of the components entering into the cranial nerves of the THE CRANIAL NERVES. 435 amphibia (Strong) and fishes (Herrick) must supply a basis, since as yet a direct analysis of the mammalian nerves has not been made. In the forms named it has been found that three different components enter into the formation of the dorsal roots of the cranial nerves: (i) fibers belonging to a general cutaneous or somatic sensory system, distributed to the skin without being connected with any special sense-organs; (2) fibers belonging to what is termed the communis or viscero-sensory system, distributed to the walls of the mouth and pharyngeal region and to special organs found in the skin of the same character as those occurring in the mouth; and (3) fibers belonging to a special set of cutaneous sense-organs largely developed in the fishes and known as the organs of the lateral line. The fibers of the somatic sensory system converge to a group of cells, situated in the lateral part of the floor of the fourth ventricle, and forming what is termed the tri- geminal lobe, and also extend posteriorly in the substance of the medulla (Fig. 231), forming what has been termed the ascending root of the trigeminus and terminating in a column of cells which represents the forward continuation of the posterior horn of the cord. In the fishes and am- phibia fibers belonging to this system are to be found in the fifth, seventh, and tenth nerves, but in the mamma- lia their distribution has apparently become more limited, being confined almost exclusively to the trigeminus, of whose sensory divisions they form a very considerable part. Since the cells around which the fibers of the ascending root of the trigeminus terminate are the forward continua- tions of the posterior horns of the cord, it seems probable that the fibers of this system are the cranial representa- tives of the posterior roots of the spinal nerves, which, it may be noted, are also somatic in their]distribution. 436 THE DEVELOPMENT OF THE HUMAN BODY. The fibers of the viscerosensory system are found in the lower forms principally in the ninth and tenth nerves (see Fig. 231), although groups of them are also incorpor- ated in the seventh and fifth. They converge to a mass of cells, known as the lobus vagi, and like the first set are also continued down the medulla to form a tract rL&L cc rix Fig. 231. — Diagram showing the Sensory Components of the Cranial Nerves op a Fish (Menidia). The somatic sensory system is unshaded, the viseero-sensory is cross- hatched, and the lateral line system is black, asc.v, Ascending root of trigeminus; brx, branchial branches of vagus; ol, olfactory bulb; op, optic nerve; rc.x, cutaneous branch of the vagus; rix, intestinal branch of vagus ; rl, lateral line nerve ; rl.acc, accessory lateral line nerve; ros, superficial ophthalmic; rp, ramus palatinus of the facial; thy, hyomandibular branch of the facial; t.inf, infraorbital nerve. — (Herrick.) known as the fasciculus solitarius or fasciculus communis . In the mammalia the system is represented by the sensory fibers of the glossopharyngeo- vagus set of nerves, of which it represents practically the entire mass; by the sensory fibers of the facial arising from the geniculate ganglion and included in the chorda tympani and probably also the THE CRANIAL NERVES. 437 great superficial petrosal ; and also, probably, by the lin- gual branch of the trigeminus. Furthermore, since the mucous membrane of the palate is supplied by branches from the trigeminus which pass by way of the spheno- palatine (Meckel's) ganglion, and the same region is sup- plied in lower forms by a palatine branch from the facial, it seems probable that the palatine nerves of the mam- malia are also to be assigned to this system.* If this be the case, a very evident clue is afforded to the homologies of the system in the spinal nerves, for since the spheno- palatine ganglion is to be regarded as part of the sympa- thetic system, the sensory fibers which pass from the vis- cera to the spinal cord by way of the sympathetic system (p. 443) present relations practically identical with those of the palatine nerves. Finally, with regard to the system of the lateral line, there seems but little doubt that it has no representation whatsoever in the spinal nerves. It is associated with a peculiar system of cutaneous sense-organs found only in aquatic or marine animals, and also with the auditory and possibly the olfactory organs, the former of which are certainly and the latter possibly primarily parts of the lateral line system of organs. The organs are principally confined to the head, although they also extend upon the trunk, where they are followed by a branch from the vagus nerve, the entire system being accordingly supplied by cranial nerves. In the fishes, in which the develop- ment of the organs is at a maximum, fibers belonging to the system are found in all the branchiomeric nerves and * The fact that the palatine branches are associated with the tri- geminus in the Mammalia and with the facial in the Amphibia is readily- explained by the fact that in the latter the Gasserian and geniculate ganglia are not always separated, so that it is possible for fibers origi- nating from the compound ganglion to pass into either nerve. 438 THE DEVELOPMENT OF THE HUMAN BODY. all converge to a portion of the medulla known as the tuberculum acusticum. In the Mammalia, with the disap- pearance of the lateral line organs there has been a disap- pearance of the associated nerves, and the only represen- tatives of the system which persist are the auditory and olfactory nerves. The table given on page 433 may now be expanded as follows, though it must be recognized that such an analy- sis of the mammalian nerves is merely a deduction from what has been observed in lower forms, and may require some modifications when the components have been sub- jected to actual observation : Nerve. Ventral Motor. Lateral Motor. Somatic Sensory. Visceral Sensory. Lateral Line. I. + III. + — — — IV. + . — — . — — V. VI. + .+ + + • — VII. VIII. + — + + IX.) &) — + + — XII. + — — Spinal. + (?) + + — An additional word is necessary concerning the spinal accessory nerve, for it presents certain interesting rela- tions which possibly furnish a clue to the spinal equiva- lents of the lateral motor roots. In the first place, the neuroblasts which give rise to those fibers of the nerve which come from the spinal cord are situated in the dorsal part of the ventral zones and in the adult in the lateral horn of the cord. As the nuclei of origin are traced ante- riorly they will be found to change their position some- THE CRANIAL NERVES. 439 what as the medulla is reached and eventually come to lie in the reticular formation, the most anterior of them being practically continuous with the motor nucleus of the vagus. Indeed, it seems probable that certain nerve- roots belonging to the vagus set, which occur in the lower vertebrates immediately behind the motor roots of the vagus and are termed the spino-occipital nerves (Fur- bringer), are incorporated in the spinal accessory of higher forms and constitute the portion of that nerve which sup- plies the sterno-mastoid and trapezius muscles. It is believed that the white rami communicantes which pass from the spinal cord to the thoracic and upper lumbar sympathetic ganglia arise from cells situated in the dorso-lateral portions of the ventral horns, and since these rami are lacking in the region in which the spinal ac- cessory occurs, it would seem that this nerve may represent the white rami of the cervical segments. The temptation is great to carry this line of homology to its conclusion, and to regard the cranial lateral motor roots as equivalent to the white rami of the cord, and the temptation is intensi- fied when it is recalled that there are both embryological and topographical reasons for regarding the branchiomeric muscles, to which the cranial lateral motor nerves are supplied, as equivalent to the visceral muscles of the trunk. But in view of the fact that a sympathetic neu- rone is always interposed between a white ramus fiber and the visceral musculature, while the lateral motor fibers connect directly with the branchiomeric musculature, it seems advisable to await further studies before yielding to the temptation. As regards the actual development of the cranial nerves, they follow the general law which obtains for the spinal nerves, the motor fibers being outgrowths from neuro- blasts situated in the walls of the neural tube, while the 44-0 THE DEVELOPMENT OF THE HUMAN BODY. sensory nerves are outgrowths from the cells of ganglia situated without the tube. In the lower vertebrates a series of ganglia, known as the suprabranchial ganglia, are developed from the ectoderm along a line corresponding with the level of the auditory invagination, while on a line corresponding with the upper extremities of the branchial clefts another series occurs which has been termed that of the epibranchial ganglia, and with both of these sets the cranial nerves are in connection. In the mammalia these structures have not yet been sufficiently studied, but from the general relationship of the suprabranchial ganglia it seems probable that they are associated with the lateral line nerves and are consequently represented in the mam- malia only by the ganglia of the auditory nerve. From what has been said above it is clear that the usual ar- rangement of the cranial nerves in twelve pairs does not repre- sent their true relationships with one another. The various pairs are serially homologous neither with one another nor with the typical spinal nerves, nor can they be regarded as repre- senting twelve cranial segments. Indeed, it would seem that comparatively little information with regard to the number of myotomic segments which have fused together to form the head is to be derived from the cranial nerves, for while there are only four of these nerves which are associated with structures equiv- alent to the mesodermic somites of the trunk, a much greater number of head cavities or mesodermic somites has been ob- served in the cranial region of the embryos of the lower verte- brates, Dohrn, for instance, having found nineteen and Killian eighteen in the cranial region of Torpedo. Furthermore, it is not possible to say at present whether the branchiomeres and their associated nerves correspond with one or several of the cranial mesodermic somites, or whether, indeed, any corre- spondence whatever exists. In early stages of development a series of constrictions have been observed in the cranial portion of the neural tube and have been regarded as indicating a primitive segmentation of that structure. The neuromeres, as the intervals between successive constrictions have been termed, seem to correspond with the cranial nerves as usually recognized and hence cannot be re- THE SYMPATHETIC SYSTEM. 44 1 garded as primitive segmental structures. They are more probably secondary and due to the arrangement of the neuro- blasts corresponding to the various nerves. The Development of the Sympathetic Nervous System. — From the embryological standpoint the distinction which has been generally recognized between the sympathetic and central nervous systems does not exist, the former having been found to be an outgrowth from the periph- eral ganglia of the latter. This mode of origin has been observed with especial clearness in the embryos of some of the lower vertebrates, in which masses of cells have been seen to separate from the posterior root ganglia to form the ganglia of the ganglionated cord (Fig. 232). In the mammalia, including man, the relations of the two sets of ganglia to one another is by no means so apparent, since the sympathetic cells, instead of being separated from the posterior root ganglion en masse, migrate from it singly or in groups, and are therefore less readily distinguishable from the surrounding mesodermal tissues. To understand the development of the sympathetic system it must be remembered that it consists typically of three sets of ganglia. One of these is constituted by the ganglia of the ganglionated cord (Fig. 233, GC), the second is represented by the ganglia of the prevertebral plexuses (PVG), such as the cardiac, solar, hypogastric, amd pelvic, while the third or peripheral set (PG) is formed by the cells which occur throughout the tissues of proba- bly most of the visceral organs, either in small groups or scattered through plexuses such as the Auerbach and Meissner plexuses of the intestine. Each cell in these various ganglia stands in direct contact with the axis- cylinder of a cell situated in the central nervous system, probably in the lateral horn of the spinal cord or the cor- responding region of the brain, so that each cell forms the 37 I 4 : -"',--^f- ft ^ • ^ Fig. 232. — Transverse Section through an Embryo Shark (Scyllium) OF 15 MM., SHOWING THE ORIGIN OF A SYMPATHETIC GANGLION. Ch, Notochord; E, ectoderm; G, posterior root ganglion; Gs, sympathetic ganglion; M, spinal cord. — (Onodi.) 442 THE SYMPATHETIC SYSTEM. 443 terminal link of a chain whose first link is a neurone belonging to the central system (Huber). Throughout the thoracic and upper lumbar regions of the body the central system neurones form distinct cords known as the white rami communicantes (Fig. 233, WR), which pass from the spinal nerves to the adjacent ganglia of the gan- glionated cord, some of them terminating around the cells of these ganglia, others passing on to the cells of the pre- vertebral ganglia, and others to those of the peripheral Fig. 233. — Diagram showing the Arrangement of the Neurones of the Sympathetic System. The fibers from the posterior root ganglia are represented by the broken black lines; those from the anterior horn cells by the solid black; the white rami by red; and the sympathetic neurones by blue. DR, Dorsal ramus of spinal nerve ; GC, ganglionated cord ; GR, gray ramus communicans; PG, peripheral ganglion; PVG, prevertebral ganglion ; VR, ventral ramus of spinal nerve ; WR, white ramus com- municans. — (Adapted from Huber.) plexuses. In the cervical, lower lumbar and sacral regions white rami are wanting, the central neurones in the first- named region probably making their way to the sympa- thetic cells largely by way of the spinal accessory nerves, while in the lower regions they may pass down the gan- glionated cord from higher regions or may join the pre- vertebral and peripheral ganglia directly without passing through the proximal ganglia. In addition to these white 444 THE DEVELOPMENT OF THE HUMAN BODY. rami, what are known as gray rami also extend between the proximal ganglia and the spinal nerves; these are composed of fibers, arising from sympathetic cells, which join the spinal nerves in order to pass with them to their ultimate distribution. The brief description here given applies especially to the sympathetic system of the neck and trunk. Represen- tatives of the system are also found in the head, in the form of a series of ganglia connected with the trigeminus and facial nerves and known as the ciliary (lenticular), spheno-palatine, otic, and submaxillary ganglia; and, as will be seen later, there are probably some sympathetic cells which owe their origin to the root ganglia of the pneumogastric and glossopharyngeal nerves. There is nothing, however, in the head region corresponding to the longitudinal bundles of fibers which unite the various proximal ganglia of the trunk to form the ganglionated cord. The first indications of the sympathetic system are to be seen in a human embryo of about 7 mm. As the spinal nerves reach the level of the dorsal edge of the body- cavity, they branch, one of the branches continuing ven- trally in the body- wall, while the other (Fig. 234, wr) passes mesially toward the aorta, some of its fibers reaching that structure, while others bend so as to assume a longitudinal direction. These mesial branches represent the white rami communicantes, but as yet no ganglion cells can be seen in their course. The cells of the posterior root ganglia have already, for the most part, assumed their bipolar form, but among them there may still be found a number of cells in the neuroblast condition, and these (Fig. 234, s), wandering out from the ganglia, give rise to a column of cells standing in relation to the white rami. At first there is no indication of a segmental arrangement THE SYMPATHETIC SYSTEM. 445 of the cells of the column (Fig. 235), but at about the seventh week such an arrangement makes its appearance in the cervical region, and later, extends posteriorly, until the column assumes the form of the ganglionated cord. Before, however, the segmentation becomes marked, Fig. 234. — Transverse Section through the Spinal Cord of an Em- bryo op 7 MM. c, Notochord; g, posterior root ganglion; m, spinal cord; s, sympathetic cell migrating from the posterior root ganglion ; wr, white ramus. — (His.) thickenings appear at certain regions of the cell column, and from these, bundles of fibers may be seen extending ventrally toward the viscera. The thickenings represent certain of the prevertebral ganglia, and later cells wander out from them and take a position in front of the aorta. 446 THE DEVELOPMENT OF THE HUMAN BODY. In an embryo of 10.2 mm. two ganglionic masses (Fig. 2 35. P c ) occur in the vicinity of the origin of the omphalo- mesenteric artery {am), one lying above and the other below that vessel; these masses represent the ganglia of the solar plexus and have separated somewhat from the ganglionated cord, the fiber bundles which unite the upper mass with the cord representing the greater and lesser splanchnic nerves (sp), while that connected with the lower mass represents the connection of the cord with the superior mesenteric ganglion. Lower down, in the neigh- borhood of the umbilical arteries, is another enlargement of the cord (bg), which probably represents the. inferior mesenteric and hypogastric ganglia which have not yet separated from the cell column. In the cervical region a similar origin of the ganglion cells of the cardiac plexus from the cell column seems to obtain. In embryos of about 7 mm. fibers may be seen ex- tending from the column toward the heart, and, entering into close relationship with descending branches from the vagus, they form a plexus, the ganglia of which are com- posed of cells which have wandered from the cell column. The elongated courses of the cardiac sympathetic and splanchnic nerves in the adult receive an explanation from the recession of the heart and diaphragm (see p. 259 and 342), the latter process forcing downward the solar plexus, which origi- nally occupied a position opposite the region of the ganglio- nated cord from which the splanchnic nerves arise. The cells which occur in the peripheral plexuses have, in a similar manner, wandered out from their original position in the cell column. In 10 mm. embryos groups of such cells have been observed both in the lesser and greater curvatures of the stomach (Fig. 235, *), where they become connected with a plexus formed by fibers from the vagus nerves (rv). The wandering of sympa- THE SYMPATHETIC SYSTEM. 447 thetic cells into the walls of the intestine has also been observed, and they form at first a single layer in the meso- derm of the intestinal wall, only later, on the differentia- tion of the muscle layers, becoming separated into the two Fig. 235. — Reconstruction op the Sympathetic System of an Em- bryo op 10.2 MM. am, Omphalomesenteric vein; ao, aorta; au, umbilical artery; bg, gan- glionic mass representing the pelvic plexus ; d, intestine ; oe, oesopha- gus ; pc, ganglia of the coeliac plexus ; ph, pharynx ; rv, right vagus nerve; sp, splanchnic nerves; sy, ganglionated cord; /, trachea; *, per- ipheral sympathetic ganglia in the walls of the stomach. — {His, Jr.) 448 THE DEVELOPMENT OF THE HUMAN BODY. layers which constitute the plexuses of Auerbach and Meissner. Similarly cells reach the heart by wandering in some cases along fibers of the vagus, although they really come from the cervical region of the ganglionated cord, and, having in their wandering met with fibers of the vagus, make use of them as paths by which they may reach their destination. As regards the cephalic sympathetic ganglia, the ob- servations of Remak on the chick and Kolliker on the rabbit show that the ciliary, sphenopalatine, and otic ganglia arise by the separation of cells from the Gasserian ganglion, and from their adult relations it may be sup- posed that the cells of the submaxillary and sublingual ganglia have similarly arisen from the geniculate ganglion of the facial nerve. Evidence has also been obtained from human embryos that sympathetic cells are derived from the ganglia of the vagus and glossopharyngeal nerves, but, instead of forming distinct ganglia in the adult, these, in all probability, associate themselves with the first cervical ganglia of the ganglionated cord. Accessory Organs of the Sympathetic System. — In addi- tion to the various sets of ganglia which clearly belong to the sympathetic system, there occur throughout the body, in various regions, certain peculiar organs which are closely associated with the same system both in their origin and in their adult relations, but whose exact phys- iological significance is as yet problematical. The Ganglia Intercarotica. — These structures, which are frequently though incorrectly termed carotid glands, are small bodies about 5 mm. in length, which lie usually to the mesial side of the upper ends of the common carotid arteries. They possess a very rich arterial supply and stand in intimate relation with the branches of an inter- ACCESSORY SYMPATHETIC ORGANS. 449 carotid sympathetic plexus, and, furthermore, they are characterized by possessing as their specific constituents markedly chromaffine cells (see p. 392), among which are scattered stellate cells resembling the cells of the sympa- thetic ganglia. They have been found to arise in pig embryos of 44 mm. by the separation of cells from the ganglionic masses scat- Fig. 236. — Section of a Cell Ball from the Intercarotid Ganglion of Man. be, Blood capillaries; ev, efferent vein; S, connective-tissue septum; /, trabecular. — {From Bbhm and Davidoff, after Schaper.) tered throughout the intercarotid sympathetic plexuses. These cells, which become the chromaffine cells, arrange themselves in round masses termed cell balls, many of which unite to form each ganglion, and in man each cell ball becomes broken up into trabecular by the blood- vessels (Fig. 236) which penetrate its substance, and the 38 450 THE DEVELOPMENT OF THE HUMAN BODY. individual balls are separated from one another by con- siderable quantities of connective tissue. Some confusion has existed in the past as to the origin of this structure. The mesial wall of the proximal part of the internal carotid artery becomes considerably thickened during the early stages of development and the thickening is traversed by numer- ous blood lacunae which communicate with the lumen of the vessel. This condition is perhaps a relic of the branchial capil- laries which in the lower gill-breathing vertebrates represent, the proximal portion of the internal carotid and has nothing to do with the formation of the intercarotid ganglion, although it has been believed by some authors (Schaper) that the ganglion was derived from the thickening of the wall of the vessel. The fact that in some animals, such as the rat and the dog, the gan- glion stands in relation with the external carotid and receives its blood-supply from that vessel is of importance in this con- nection. The thickening of the internal carotid disappears in the higher vertebrates almost entirely, but in the Amphibia it persists throughout life, the lumen of the proximal part of the vessel being converted into a fine meshwork by the numerous tra- becular which traverse it. This carotid labyrinth has been termed the carotid gland, a circumstance which has probably assisted in producing confusion as to the real significance of the intercarotid ganglion. The Organs of Zuckerkandl. — In embryos of 14.5 mm. there have been found, in front of the abdominal aorta, closely packed groups of cells which resemble in appear- ance the cells, composing the ganglionated cord, two of these groups, which extend downward along the side of the aorta to below the point of origin of the inferior mesen- teric artery, being especially distinct. These cell groups give rise to the ganglia of the praevertebral sympathetic plexuses and also to peculiar bodies which, from their discoverer, may be termed the organs of Zuckerkandl. Each body stands in intimate relation with the fibers of the sympathetic plexuses and has a rich blood-supply, ACCESSORY SYMPATHETIC ORGANS. 451 resembling in these respects the intercarotid ganglia, and the resemblance is further increased by the fact that the specific cells of the organ are markedly chromaffine. Fig. 237. — Accessory Sympathetic Organs op Zuckerkandl from a New-born Child. a, Aorta; ci, inferior vena cava; i.c, common iliac artery; mi, inferior mesenteric artery; n.l and n.r, left and right accessory organs; pl.a, aortic plexus; u, ureter; v.r.s, left renal vein. — {Zuckerkandl.) At birth the bodies situated in the upper portion of the abdominal cavity have broken up into small masses, but the two lower ones, mentioned above, are still well defined (Fig. 237). Even these, however, seem to disappear later 452 THE DEVELOPMENT OF THE HUMAN BODY. on and no traces of them have as yet been found in the adult. The Coccygeal or Luschka's Ganglion. — In embryos of about 1 5 cm. there is to be found on the ventral surface of the apex of the coccyx a small oval group of polygonal cells, clearly separated from the surrounding tissue by a mesenchymal capsule. Later, connective-tissue trabe- culae make their way into the mass, which thus becomes divided into lobules, and, at the same time, a rich vascu- lar supply, derived principally from branches of the arteria sacra media, penetrates the body which thus as- sumes the adult condition, in which it presents a general resemblance to the intercarotid ganglion. There are as yet no direct observations determining the origin of the specific cells of this coccygeal gland, but the evidence available points to their derivation from the sympathetic system. They appear in the position which should be occupied by the terminal portion of the sympa- thetic cord, and from the time when they first become recognizable onward they are connected with sympathetic fibers. The probability is that, like the cells of the other organs described above, they are derived from sympa- thetic ganglia. LITERATURE. W. His : " Zur Geschichte des menschlichen Riickenmarkes und der Ner- venwurzeln," Abhandl. der konigl. Sachsischen Gesellsch., Math.- Physik. Classe, xin, 1886. W. His: "Zur Geschichte des Gehirns sowie der centralen und peripher- ischen Nervenbahnen beim menschlichen Embryo," Abhandl. der konigl. Sachsischen Gesellsch., Math.-Physih. Classe, xiv, 1888. W. His: "Die Formentwickelung des menschlichen Vorderhirns vom Ende des ersten bis zum Beginn des dritten Monats," Abhandl. der konigl. Sachsischen Gesellsch., Math.-Physik. Classe, xv, 1889. W. His: "Histogenese und Zusammenhang der Nervenelemente," Archiv fur Anat. und Physiol., Anat. Abth., Supplement, 1890. LITERATURE. 453 W. His, Jr.: "Die Entwickelung des Herznervensystems bei Wirbel- thieren," Abhandl. der konigl. Sachsischen Gesellsch., Math.-Physik. Classe, xviii, 1893 W. His, Jr. : " Ueber die Entwickelung des Bauchsympathicus beim Hiihn- chen und Menschen," Archiv fur Anat. und Physiol., Anat. Abth., Supplement, 1897. C. J. Hbrrick: "The Cranial and First Spinal Nerves of Menidia: A Con- tribution upon the Nerve Components of the Bony Fishes," Journ. of Comp. Neurol., ix, 1899. C. J. Hbrrick: "The Cranial Nerves and Cutaneous Sense-organs of the North American Siluroid Fishes," Journ. of Comp. Neurol., xi, 1901. G. C. Huber: "Four Lectures on the Sympathetic Nervous System," Journ. of Comp. Neurol., vn, 1897. J. H. Jakobsson: "Beitrage zur Kenntniss der fotalen Enlwicklung der Steissdruse," Archiv fur mikrosk. Anat., Mil, 1899. A. Kohn: "Ueber den Bau und die Entwickelung der sog. Carotisdriise," Archil), fur mikrosk. Anat., vn, 1900. M. von LEnhossEk: "Die Entwickelung der Ganglienanlagen bei dem menschlichen Embryo," Archiv fur Anat. und Physiol., Anat. Abth., 1891. F. Marchand: "Ueber die Entwickelung des Balkens im menschlichen Gehirn," Archiv fur mikrosk. Anat., xxxvn, 1891. V. von Mihalkovicz: " Entwickelungsgeschichte des Gehirns," Leipzig, 1877. A. D. Onodi: "Ueber die Entwickelung des sympatfrischen Nervensys- tems," Archiv fur mikrosk. Anat., xxvn, 1886. G. Retzius: " Das Menschenhirn," Stockholm, 1896. A. SchapER: " Die fruhesten Differenzirungsvorgange im Centralnerven- system," Archiv fur Entwicklungsmechanik, v, 1897. O. S. Strong: " The Cranial Nerves of Amphibia," Journal of Mor- phol., x, 1895. R. Wlassak: " Die Herkunft des Myelins," Archiv fur Entwicklungsme- ehanik, vi, 1898. E Zuckerkandl : " Ueber Nebenorgane des Sympathicus im Retroperi- tonealraum des Menschen," Verhandl. Anat. Gesellsch., xv, 1901. CHAPTER XV. THE DEVELOPMENT OF THE ORGANS OF SPECIAL SENSE. Like the cells of the central nervous system, the sensory cells are all of ectodermal origin, and in lower animals, such as the earthworm, for instance, they retain their orig- inal position in the ectodermal epithelium throughout life. In the vertebrates, however, the majority of the sen- sory cells relinquish their superficial position and sink more or less deeply into the subjacent tissues, being repre- sented by the posterior root ganglion cells and by the sen- sory cells of the special sense-organs, and it is only in the olfactory organ that the original condition is retained. Those cells which have withdrawn from the surface re- ceive stimuli only through an overlying cell or cells, and in certain cases these transmitting cells are not specially differentiated, the terminal branches of the sensory den- drites ending among ordinary epithelial cells or in such structures as the Pacinian bodies or the end-bulbs of Krause situated beneath undifferentiated epithelium. In other cases, however, certain specially modified super- ficial cells serve to transmit the stimuli to the peripheral sensory neurones, forming such structures as the hair-cells of the auditory epithelium or of the taste-buds. Thus three degrees of differentiation of the special sen- sory cells may be recognized and a classification of the sense-organs may be made upon this basis. One organ, however, the eye, cannot be brought into such a classifica- tion, since its sensory cells present certain developmental 454 THE OLFACTORY NERVE. 455 peculiarities which distinguish them from those of all other sense-organs. Embryologically the retina is a portion of the central nervous system and not a peripheral organ, and hence it will be convenient to arrange the other sense- organs according to the classification indicated and to discuss the history of the eye at the close of the chapter. The Development of the Olfactory Organ. — The general development of the nasal fossa, the epithelium of which contains the olfactory sense cells, has already been de- scribed (pp. 97 and 104), as has also the development of the olfactory lobes of the brain (p. 427), and it remains to consider here merely the formation of the olfactory nerve and the development of the rudimentary organ of Jacob- son. The Olfactory Nerve. — Very diverse results have been obtained by various observers of the development of the olfactory nerve, it having been held at different times that it was formed by the outgrowth of fibers from the olfac- tory lobes (Marshall), from fibers which arise partly from the olfactory lobes and partly from the olfactory epithe- lium (Beard), from the cells of an olfactory ganglion origi- nally derived from the olfactory epithelium but later separating from it (His), and, finally, that it was composed of the prolongations of certain cells situated and, for the most part at least, remaining permanently in the olfactory epithelium (Disse). The most recent observations on the structure of the olfactory epithelium and nerve indicate a greater amount of probability in the last result than in the others, and the description which follows will be based upon the observations of His, modified in conformity with the results obtained by Disse from chick embryos. In human embryos of the fourth week the cells lining the upper part of the olfactory pits show a distinction into ordinary epithelial and sensory cells, the latter, when fully 456 THE DEVELOPMENT OF THE HUMAN BODY. formed, being elongated cells prolonged peripherally into a short but narrow process which reaches the surface of the epithelium and proximally gives rise to an axis- cylinder process which extends up toward and penetrates Fig. 238. — Diagram Illustrating the Relations of the Fibers of the Olfactory Nerve. Ep, Epithelium of the olfactory pit ; C, cribriform plate of the ethmoid ; G, glomerulus of the olfactory bulb; M, mitral cell. — {Van Gehuchten.) the tip of the olfactory lobe to come into contact with the dendrites of the first central neurones of the olfactory tract (Fig. 238). These cells constitute a neuro-epithelium and in later stages of development retain their epithelial THE ORGAN OF JACOBSON. 457 position for the most part, a few of them, however, with- drawing into the subjacent mesenchyme and becoming bipolar, their peripheral prolongations ending freely among the cells of the olfactory epithelium. These bi- polar cells resemble closely in form and relations the cells of the embryonic posterior root ganglia, and thus form an interesting transition between these and the neuroepithe- lial cells. The Organ of Jacobson. — In embryos of three or four months a small pouch-like invagination of the epithelium covering the lower anterior portion of the median septum of the nose can readily be seen. This becomes converted into a slender pouch, 3 to 5 mm. long, ending blindly at its posterior extremity and opening at its other end into the nasal cavity. Its lining epithelium resembles that of the respiratory portion of the nasal cavity, and there is devel- oped in the connective tissue beneath its floor a slender plate of cartilage, distinct from that forming the septum of the nose. This organ, which may apparently undergo degenera- tion in the adult, and in some cases completely disap- pears, appears to be the representative of what is known as Jacobson's organ, a structure which reaches a much more extensive degree of development in many of the lower mammals, and in these contains in its epithelium sensory cells whose axis-cylinder processes pass with those of the olfactory sense cells to the olfactory bulbs. In man, how- ever, it seems to be a rudimentary organ, and no satisfac- tory explanation of its function has as yet been advanced. The olfactory neuro-epithelium, considered from a comparative standpoint, seems to have been derived from the system of lateral line organs so highly developed in the lower vertebrates. In higher forms the system, which is cutaneous in character, has disappeared except in two 458 THE DEVELOPMENT OF THE HUMAN BODY. regions where it has become highly specialized. In one of these regions it has given rise to the olfactory sense cells and in the other to the similar cells of the auditory appara- tus. The Organs of Touch and Taste. — Nothing is yet known concerning the development of the various forms of tactile organs, which belong to the second class of sensory organs described above. The Organs of Taste. — The remaining organs of special sense belong to the third class, and of these the organs of taste present in many respects the simplest condition. They are developed principally in connection with the B Fig. 239. — Diagrams Representing the Development op a Circum- vallate Papilla. a, Valley surrounding the papilla; b, von Ebner's gland. — (Graberg.) circumvallate and foliate papillae of the tongue, and of the former one of the earliest observed stages has been found in embryos of 9 cm. in the form of two ridges of epidermis, lying toward the back part of the tongue and inclined to one another in such a manner as to form a V with the apex directed backward. From these ridges solid down- growths of epidermis into the subjacent tissue occur, each downgrowth having the form of a hollow truncated cone with its basal edge continuous with the superficial epider- mis (Fig. 239, A). In later stages lateral outgrowths de- velop from the deeper edges of the cone, and about the same time clefts appear in the substance of the original THE ORGANS OF TASTE. 459 downgrowths (Fig. 239, B) and, uniting together, finally- open to the surface, forming a trench surrounding a pa- pilla (Fig. 239, C). The lateral outgrowths, which are at first solid, also undergo an axial degeneration and become converted into the glands of Ebrier (b), which open into the trench near its floor. The various papillae which occur in the adult do not develop simultaneously, but their num- ber increases with the age of the fetus, and there is, more- over, considerable variation in the time of their develop- ment. The taste-buds are formed by a differentiation of the epithelium which covers the papillae, and this differentia- tion appears to stand in intimate relation with the pene- tration of fibers of the glossopharyngeal nerve into the pa- pillae. The buds form at various places upon the papillae, and at one period are especially abundant upon their free surfaces, but in the later weeks of intrauterine life these surface buds undergo degeneration and only those upon the sides of the trench persist, as a rule. The foliate papillae do not seem to be developed until some time after the circumvallate, being entirely wanting in embryos of four and a half and five months, although plainly recognizable at the seventh month. The Development of the Ear. — It is customary to de- scribe the mammalian ear as consisting of three parts, known as the inner, middle, and outer ears, and this divi- sion is, to a certain extent at least, confirmed by the em- bryonic development. The inner ear, which is the sen- sory portion proper, is fundamentally an ectodermal structure, secondarily becoming deeply seated in the mesodermal tissue of the head, while the middle and outer ears, which provide the apparatus necessary for the con- duction of the sound-waves to the inner ear, are modified portions of the anterior branchial arches. It will be con- 460 THE DEVELOPMENT OF THE HUMAN BODY. venient, accordingly, in the description of the ear, to ac- cept the usually recognized divisions and to consider first of all the development of the inner ear, or, as it is better termed, the otocyst. The Development of the Otocyst. — In an embryo of 2.4 mm. a pair of pits occur upon the surface of the body about opposite the middle portion of the hind-brain (Fig. 240, A). The ectoderm lining the pits is somewhat thicker than is the neighboring ectoderm of the surface of the body, and, from analogy with what occurs in other vertebrates, it seems probable that the pits are formed by the invagination of localized thickenings of the ectoderm. Fig. 240. — Transverse Section Passing through the Otocyst (ot) of Embryos of (A) 2.4 mm. and (B) 4 mm. — (His.) The mouth of each pit gradually becomes smaller, until finally the invagination is converted into a closed sac (Fig. 240, B), which separates from the surface ectoderm and becomes enclosed within the subjacent mesoderm. This sac is the otocyst, and in the stage just described, found in embryos of 4 mm., it has an oval or more or less spheri- cal form. Soon, however, in embryos of 6.9 mm., a pro- longation arises from its dorsal portion and the sac as- sumes the form shown in Fig. 241, A; this prolongation represents the ductus endolymphaticus, and, increasing in length, it soon becomes a strong club-shaped process, pro- jecting considerably beyond the remaining portions of the THE INTERNAL EAR. 461 otocyst (Fig. 241, B). In embryos of about 10.2 mm. the sac begins to show certain other irregularities of shape (Fig. 241, B, sc). Thus, about opposite the point of origin of the ductus endolymphaticus three folds make their appearance, representing the semicircular canals, and as Fig. 241. — Reconstructions of the Otocysts of Embryos of (A) 6.9 MM- and (D) 10.2 MM. de, Endolymphatic duct; gc, ganglion cochleare; gg, ganglion genicula- tum ; gv, ganglion vestibulare ; sc, horizontal semicircular canal. — (His, Jr.) they increase in size the opposite walls of the central por- tion of each fold come together, fuse, and finally become absorbed, leaving the free edge of the fold as a crescentic canal, at one end of which an enlargement appears to form the ampulla. The transformation of the folds into canals takes place somewhat earlier in the cases of the two 462 THE DEVELOPMENT OF THE HUMAN BODY. vertical than in that of the horizontal canal, as may be seen from Fig. 242, which represents the condition oc- curring in an embryo of 13.5 mm. A short distance below the level at which the canals communicate with the re- maining portion of the oto- cyst a constriction appears, indicating a separation of the otocyst into a more dorsal portion, which becomes the utriculus, and a more ventral one. Later, the ventral por- tion of the latter begins to be prolonged into a flattened canal which, as it elongates, becomes coiled upon itself and also becomes separated by a constriction from the portion of the otocyst from which it arises. The latter is the representative of the adult sacculus (Fig. 243, s), while the coiled canal (co) forms the scala media of the cochlea and the constricted portion of the otocyst, which unites the scala and the sac- culus, becomes the canalis reuniens. The constriction which marks the line of sep- aration of the utriculus (ut) and sacculus is converted into a narrow canal with which the ductus endolymph- aticus connects, and hence it is that, in the adult, the connection between these two portions of the otocyst Fig. 242. — Reconstruction op the Otocyst of an Embryo of 13.5 MM. co, Cochlea; de, endolymphatic duct; sc, semicircular canal. —(.His, Jr.) THE INTERNAL EAR. 463 seems to be formed by the ductus dividing proximally into two limbs, one of which is connected with the utri- cle and the other with the saccule. When first observed in the human embryo the auditory ganglion is closely associated with the geniculate ganglion of the seventh nerve (Fig. 241, B), the two, usually spoken of as the acustico-facialis ganglion, forming a mass Fig. 243. — Reconstruction of the Otocyst of an Embryo of 22 mm. co, Cochlea ; de, endolymphatic duct ; s, sacculus ; ut, utriculus. — (His, Jr.) of cells lying in close contact with the anterior wall of the otocyst. The origin of the ganglionic mass has not yet been traced in the mammalia, but it has been observed that in cow embryos the geniculate ganglion is connected with the ectoderm at the dorsal end of the first branchial cleft (Froriep), and it may perhaps be regarded as one of 464 THE DEVELOPMENT OF THE HUMAN BODY. the epibranchial ganglia (see p. 440), and in the lower vertebrates a union of the ganglion with a suprabranchial ganglion has been observed (Kupfer), this union indicat- ing the origin of the auditory ganglion from one or more of the ganglia of the lateral line system. At an early stage in the human embryo the auditory ganglion shows indications of a division into two portions, a more dorsal one, which represents the future ganglion vestibulare, and a ventral one, the ganglion cochleare. The ganglion cells become bipolar, in which condition they remain throughout life, never reaching the T-shaped condition found in most of the other peripheral cerebro- spinal ganglia. One of the prolongations of each cell is directed centrally to form a fiber of the auditory nerve while the other penetrates the wall of the otocyst to enter into relations with certain specially modified cells which differentiate from its lining epithelium. In the earliest stages the ectodermal lining of the oto- cyst is formed of similar columnar cells, but later over the greater part of the surface the cells flatten down, only a few, aggregated together to form patches, retaining the high columnar form and developing hair-like processes upon their free surfaces. These are the sensory cells of the ear. In the human ear there are in all six patches of these sensory cells, an elongated patch {crista acustica) in the ampulla of each semicircular canal (Fig. 244, cr), a round patch {macula acustica, mu) in the utriculus and another {ms) in the sacculus, and, finally, an elongated patch which extends the entire length of the scala media of the cochlea and forms the sensory cells of the organ of Corti. In connection with this last patch certain adjacent cells also retain their columnar form and undergo various modi- fications, giving rise to a rather complicated structure THE INTERNAL EAR. 465 whose development has been traced in the rabbit. Along the whole length of the seala media the cells resting upon that half of the basilar membrane which is nearest the axis of the cochlea, and may be termed the inner half, retain Fig. 244. — The Right Internal Ear of an Embryo of Six Months ca, ce, and cp, Anterior, external, and posterior semicircular canals; cr, crista acustica ; de, endolymphatic duct; Is, spiral ligament; mb, basilar membrane ; ms and nut, macula acustica sacculi and utri- culi; rb, basilar branches of the cochlear nerve. — (Retzius.) their columnar shape, forming two ridges projecting slightly into the cavity of the scala (Fig. 245). The cells of the inner ridge, much the larger of the two, give rise to the membrana tectoria, either as a cuticular secre- 39 466 THE DEVELOPMENT OF THE HUMAN BODY. tion or by the artificial adhesion of long hair-like processes which project from their free surfaces (Ayers). The cells of the outer ridge are arranged in six longitudinal rows (Fig. 245, 1-6); those of the innermost row (1) develop hairs upon their free surfaces and form the inner hair cells, those of the next two rows (2 and 3) gradually become transformed on their adjacent surfaces into chitinous sub- * a, . tr * ■ Fig. 245. — Section of the Scala Media of the Cochlea of a Rabbit Embryo of 55 mm. a, Mesenchyme; b to e, epithelium of scala media; M.t, membrana tec- toria; V.s.p, vein; 1 to 7, organ of Corti. — {Baginsky.) stance and form the rods of Corti, while the three outer rows (4 to 6) develop into the outer hair cells. It is in connection with the hair cells that the peripheral pro- longations of the cells of the cochlear ganglion terminate, and since these hair cells are arranged in rows extending the entire length of the scala media, the ganglion also is THE INTERNAL EAR. 467 drawn out into a spiral following the coils of the cochlea, and hence is sometimes termed the spiral ganglion. While the various changes described above have been taking place in the otocyst, the mesoderm surrounding it has also been undergoing development. At first this tissue is quite uniform in character, but later the cells immediately surrounding the otocyst condense to give rise to a fibrous layer (Fig. 246, ep) while more peripherally they become more loosely arranged and form a some- what gelatinous layer {$), and still more peripher- ally a second fibrous layer is differentiated and the remainder of the tissue assumes a charac- ter which indicates an approaching conversion into cartilage. The fur- ther history of these va- rious layers is as follows. The inner fibrous layer gives rise to the connect- ive-tissue wall which sup- ports the ectodermal lin- ing of the various por- tions of the otocyst; the gelatinous layer undergoes a degeneration to form a lymph-like fluid known as the perilymph, the space occupied by the fluid being the peri- lymphatic space; the outer fibrous layer becomes peri- chondrium and later periosteum; and the precartilage undergoes chondrification and later ossifies to form the petrous portion of the temporal bone. The gelatinous layer completely surrounds most of the otocyst structures, which thus come to lie free in the peri- Fig. 246. — Transverse Section THROUGH A SEMICIRCULAR CaNAL of a Rabbit Embryo of Twenty- four Days. c, Periotic cartilage ; ep, fibrous mem- brane beneath the epithelium of the canal; p, perichondrium; s, spongy tissue. — (Von Kblliker.) 468 THE DEVELOPMENT OF THE HUMAN BODY. lymphatic space, but in the cochlear region the conditions are somewhat different. In this region the gelatinous layer is interrupted along two lines, an outer broad one where the connective-tissue wall of the scala media is directly continuous with the perichondrium layer, and an inner narrow one, along which a similar fusion takes place with the perichondrium of a shelf -like process of the car- tilage, which later ossifies to form the lamina spiralis. Fig. 247. — Diagrammatic Transverse Section* through a Coil of the Cochlea, showing the Relations of the Scales. c, Organ of Corti ; co, ganglion cochleare ; Is, lamina spiralis ; SM, scala media; ST, scala tympani; SV, scala vestibuli. — (From Gerlach.) Consequently throughout the cochlear region the peri- lymphatic space is divided into two compartments which communicate at the apex of the cochlea, while below one, known as the scala vestibuli, communicates with the space surrounding the saccule and utricle, and the other, the scala tympani, abuts upon a membrane which separates it from the cavity of the middle ear and represents a portion THE MIDDLE EAR. 469 of the outer wall of the petrous bone where chondrification and ossification have failed to occur. This membrane closes what appears in the dried skull to be an opening in the inner wall of the middle ear, known from its shape as the fenestra rotunda; another similar opening, also closed by membrane in the fresh skull, occurs in the bony wall opposite the utricular portion of the otocyst and is known as the fenestra ovalis. The Development of the Middle Ear. — The middle ear develops from the upper part of the pharyngeal groove which represents the endodermal portion of the first branchial cleft. This becomes prolonged dorsally and at its dorsal end enlarges to form the tympanic cavity, while the narrower portion intervening between this and the pharyngeal cavity represents the Eustachian tube. To correctly understand the development of the tym- panic cavity it is necessary to recall the structures which form its boundaries. Anteriorly to the upper end of the first branchial pouch there is the upper end of the first arch, and behind it the corresponding part of the second arch, the two fusing together dorsal to the tympanic cavity and forming its roof. Internally the cavity is bounded by the outer wall of the cartilaginous investment of the otocyst, while externally it is separated from the upper part of the ectodermal groove of the first branchial cleft by the thin membrane which forms the floor of the groove. It has been seen in an earlier chapter that the axial mesoderm of each branchial arch gives rise to skeletal structures and muscles. The axial cartilage of the ventral portion of the first arch is what is known as Meckel's cartilage, but in that portion of the arch which forms the roof and anterior wall of the tympanic cavity, the car- tilage becomes constricted to form two masses which later 47° THE DEVELOPMENT OF THE HUMAN BODY. ossify to form the malleus and incus (Fig. 248, m and i), while the muscular tissue of this dorsal portion of the arch gives rise to the tensor tympani. Similarly, in the case of the second arch there is to be found, dorsal to the extrem- ity of the cartilage which forms the styloid process of the adult, a narrow plate of cartilage which forms an invest- ment for the facial nerve (Fig. 248, VII), and dorsal to Fig. 248. — Semi-diagrammatic View of the Auditory Ossicles of an Embryo of Six Weeks. i, Incus; /, jugular vein; m, malleus; mc, Meckel's cartilage; oc, capsule of otocyst ; R, cartilage of the second branchial arch ; st, stapes ; VII, facial nerve. — (Siebenmann.) this a ring of cartilage (st) which surrounds a small artery and represents the stapes, in connection with which a muscle, termed the stapedius, develops. Since, as has already been stated, the two arches meet dorsally above the primitive tympanic cavity, the struc- tures just mentioned lie embedded in the mesenchyme forming the roof of the cavity, as does also the chorda THE MIDDLE EAR. 471 , ' .' ■ v __ _/ \M '■M tympani, a branch of the seventh nerve, as it passes into the substance of the first arch on the way to its destina- tion. The mesenchyme in which these various structures are embedded is rather voluminous (Fig. 250), and after the end of the seventh month it becomes converted into a peculiar spongy tissue, which, toward the end of fetal life, gradually degenerates, the tympanic cavity at the same time expanding and wrapping itself around the ossicles and the muscles attached to them (Fig. 249). The bones and their muscles, consequently, while appearing in the adult to traverse the tympanic cavity, are really completely enclosed within a layer of epi- thelium continuous with that lining the wall of the cavity, while the handle of the mal- leus and the chorda tympani lie between the epithelium of the outer wall of the cavity and the fibrous mesoderm which forms the tympanic membrane. The extension of the tym- panic cavity does not, how- ever, cease with its replacement of the degenerated spongy mesenchyme, but toward the end of fetal life it begins to invade the substance of the temporal bone by a process similar to that which produces the ethmoidal cells and the ":;r : .py y ■-' c Fig. 249. — Diagrams Illus- trating the Mode of Ex- tension op the Tympanic Cavity Around the Audi- tory Ossicles. M, Malleus; m, spongy mesen- chyme ; p, inner surface of the periotic capsule; T, tympanic cavity. The broken line rep- resents the epithelial lining of the tympanic cavity. 472 THE DEVELOPMENT OF THE HUMAN BODY. other osseous sinuses in connection with the nasal cavities (see p. 199). This process continues for some years after birth and results in the formation in the mastoid portion of the bone of the so-called mastoid cells, which communi- cate with the tympanic cavity and have an epithelial lining continuous with that of the cavity. The lower portion of the diverticulum from the first pharyngeal groove which gives rise to the tympanic cavity becomes converted into the Eustachian tube. During development the lumen of the tube disappears for a time, probably owing to a proliferation of its lining epithelium, but it is re-established before birth. In the account of the development of the ear-bones given above it is held that the malleus and incus are derivatives of the first branchial (mandibular) arch and the stapes of the second. This view represents the general consensus of recent workers on the difficult question of the origin of these bones, but it should be mentioned that nearly all possible modes of origin have been at one time or other suggested. The malleus has very generally been accepted as coming from the first arch, and the same is true of the incus, although some earlier authors have assigned it to the second arch. But with regard to the stapes the opin- ions have been very varied. It has been held to be derived from the first arch, from the second arch, from neither one nor the other, but from the cartilaginous investment of the otocyst, or, finally, it has been held to have a compound origin, its arch being a product of the second arch while its basal plate was a part of the otocyst investment. Recent observations seem to place its independence of the otocyst investment beyond doubt, in which case its origin from the second arch seems fairly certain. The Development of the Tympanic Membrane and of the Outer Ear. — Just as the tympanic cavity is formed from the endodermal groove of the first branchial cleft, so the outer ear owes its origin to the ectodermal groove of the. same cleft and to the neighboring arches. The dorsal and most ventral portions of the groove flatten out and THE EXTERNAL EAR. 473 disappear, but the median portion deepens to form at about the end of the second month, a funnel-shaped cavity which corresponds to the outer portion of the ex- ternal auditory meatus. From the inner end of this a 3 — me ' ':■''-■ Fig. 250. — Horizontal, Section Passing through the Dorsal Wall of the External Auditory Meatus in an Embryo of 4.5 cm. c, Cochlea ; de, endolymphatic duct ; i, incus ; Is, lateral sinus ; m, malleus ; me, meatus auditorius externus ; me', cavity of the meatus ; s, sac- culus; sc, horizontal semicircular canal; sc', posterior semicircular canal; st, stapes; t, tympanic cavity; u, utriculus; 7, facial nerve. — (Siebenmann.) solid ingrowth of ectoderm takes place, and this, enlarging at its inner end to form a disk-like mass, comes into rela- tion with the gelatinous mesoderm which surrounds the malleus and chorda tympani. At about the seventh 4 o 474 THE DEVELOPMENT OF THE HUMAN BODY. month a split occurs in the disk-like mass (Fig. 250), separating it into an outer and an inner layer, the latter of which becomes the outer epithelium of the tympanic membrane. Later, the split extends outward in the sub- stance of the ectodermal ingrowth and eventually unites with the funnel-shaped cavity to complete the external meatus. The tympanic membrane is formed in considerable part from the substance of the first branchial arch, the area in which it occurs not being primarily part of the wall of the tympanic cavity, but being brought into it secondarily by the expansion of the cavity. The membrane itself is mesodermal in origin and is lined on its outer surface by an ectodermal and on the inner by an endodermal epi- thelium. The pinna owes its origin to the portions of the first and second arches which bound the entrance of the external meatus. Upon the posterior edge of the first arch there appear about the end of the fourth week two transverse furrows which mark off three tubercles (Fig. 251, A, 1-3) and on the anterior edge of the second arch a correspond- ing number of tubercles (4-6) is formed, while, in addition, a longitudinal furrow, running down the middle of the arch, marks off a ridge (c) lying posterior to the tubercles. From these six tubercles and the ridge are developed the various parts of the pinna, as may be seen from Fig. 251. The most ventral tubercle of the first arch (1) gives rise to the tragus, and the middle one (5) of the second arch fur- nishes the antitragus. The middle and dorsal tubercles of the first arch (2 and 3) unite with the ridge (c) to produce the helix, while from the dorsal tubercle of the second arch (4) is produced the antihelix and from the ventral one (6) the lobule. It is noteworthy that at about the third month of development the upper and posterior portion of THE EXTERNAL EAR. 475 the helix is bent forward so as to conceal the antihelix ; it is at just about a corresponding stage that the pointed form of the ear seen in the lower mammals makes its appearance, and it is evident that, were it not for the for- ward bending, the human ear would also be assuming at Fig. 251. — Stages in the Development of the Pinna. A, Embryo of 1 1 mm. ; B, of 13.6 mm. ; C, of 15 mm. ; D, at the beginning of the third month; E, fetus of 8.5 cm.; F, fetus at term. — (His.) this stage a more or less pointed form. Indeed, there is usually to be found upon the incurved edge of the helix, some distance below the upper border of the pinna, a more or less distinct tubercle, known as Darwin's tubercle, which seems to represent the point of the typical mammalian 476 THE DEVELOPMENT OF THE HUMAN BODY. ear, and is, accordingly, the morphological apex of the pinna. There seems to be little room for doubt that the otocyst be- longs primarily to the system of lateral line sense-organs, but a discussion of this interesting question would necessitate a con- sideration of details concerning the development of the lower vertebrates which would be foreign to the general plan of this book. It may be recalled, however, that the analysis of the components of the cranial nerves described on page 437 refers the auditory nerve to the lateral line system. The Development of the Eye. — The first indications of the development of the eye are to be found in a pair of hollow outgrowths from the side of the first primary brain vesicle, at a level which corresponds to the junction of the dorsal and ventral zones. Each evagination is directed at first upward and backward, and, enlarging at its extrem- ity, it soon shows a differentiation into a terminal bulb and a stalk connecting the bulb with the brain (Fig. 216). At an early stage the bulb comes into apposition with the ectoderm of the side of the head, and this, over the area of contact, becomes thickened and then depressed to form the beginning of the future lens (Fig. 252). As the result of the depression of the lens ectoderm, the outer wall of the optic bulb becomes pushed inward to- ward the inner wall, and this invagination continuing until the two walls come into contact, the bulb is transformed into a double-walled cup, the optic cup, in the mouth of which lies the lens (Fig. 254). The cup is not perfect, however, since the invagination affects not only the optic bulb, but also extends inward on the posterior surface of the stalk, forming upon this a longitudinal groove and pro- ducing a defect of the ventral wall of the cup, known as the chorioidal fissure (Fig. 253). The groove and fissure become occupied by mesodermal tissue, and in this, at THE EYE. 477 about the fifth week, a blood-vessel develops which tra- verses the cavity of the cup to reach the lens and is known as the arteria hyaloidea. Fig. 252. — Early Stage in the Development of the Lens in a Rabbit Embryo. The nucleated layer to the left is the ectoderm and the thicker lens epithelium, below which is the outer wall of the optic evagination; above and below between the two is mesenchyme. — (Rabl.) In the mean time further changes have been taking place in the lens. The ectodermal depression which represents 478 THE DEVELOPMENT OF THE HUMAN BODY. it gradually deepens to form a cup, the lips of which ap- proximate and finally meet, so that the cup is converted into a vesicle which finally separates completely from the ectoderm (Fig. 254), much in the same way as the otocyst does. As the lens vesicle is constricted off, the surround- ing mesodermal tissue grows in to form a layer between it and the overlying ectoderm, and a split appearing in the layer divides it into an outer thicker portion, which rep- resents the cornea, and an inner thinner portion, which Fig. 253. — Reconstruction of the Brain of an Embryo of Four Weeks, showing the Chorioid Fissure. — (His.) covers the outer surface of the lens and becomes highly vascular. The cavity between these two portions repre- sents the anterior chamber of the eye. The cavity of the optic cup has also become filled by a peculiar tissue which represents the vitreous humor, while the mesodermal tissue surrounding the cup condenses to form a strong invest- ment for it, which is externally continuous with the cornea, and at about the sixth week shows a differentia- tion into an inner vascular layer, the chorioid coat, and an outer denser one, which becomes the sclerotic coat. THE LENS. 479 The various processes resulting in the formation of the eye, which have thus been rapidly sketched, may now be considered in greater detail. The Development of the Lens. — When the lens vesicle is complete, it forms a more or less spherical sac lying be- Fig. 254. — Horizontal Section through the; Eye of an Embryo Pig of 7 MM. Br, Thalamencephalon; Ec, ectoderm; /, lens; P, pigment, and R, retinal layers of the retina. neath the superficial ectoderm and containing in its cavity a few cells, either scattered or in groups (Fig. 254). These cells, which have wandered into the cavity of the vesicle from its walls, take no part in the further development of the lens, but early undergo complete degeneration, and 480 THE DEVELOPMENT OF THE HUMAN BODY. the first'change which is concerned with the actual forma- tion of the lens is an increase in the height of the cells forming its inner wall and a thinning out of its outer wall / (Fig. 255, A). These changes continuing, the outer half, of the vesicle becomes converted into a single layer of; somewhat flat cells which persist in the adult condition to form the anterior epithelium of the lens, while the cells of the posterior wall form a marked projection into the cav- ity of the vesicle and eventually completely obliterate it, coming into contact with the inner surface of the anterior epithelium (Fig. 255, B). These posterior elongated cells form, then, the principal mass of the lens, and constitute what are known as the lens fibers. At first those situated at the center of the pos- terior wall are the longest, the more peripheral ones gradu- ally diminishing in length until at the equator of the lens they become continuous with and pass into the anterior epithelium. As the lens increases in size, however, the most centrally situated cells fail to elongate as rapidly as the more peripheral ones and are pushed in toward the center of the lens, the more peripheral fibers meeting be- low them along a line passing across the inner surface of the lens. The disparity of growth continuing, a similar sutural line appears in the outer surface beneath the ante- rior epithelium, and the fibers become arranged in con- centric layers around a central core composed of the shorter fibers. In the human eye the line of suture of the peripheral fibers becomes bent so as to consist of two limbs which meet at an angle, and from the angle a new suturing line develops during embryonic life, so that the suture assumes the form of a three-rayed star. In later life the stars become more complicated, being either six-rayed or more usually nine-rayed in the adult condition (Fig. 256). /■-££/ v^ifllllffilfff mmmttmmm x -v / -■' : -' j -^LiliiMs Fig. 255.— vSections through the Lens ( A\ no h,™,., c WV TO T H IRT v-0 NE DA VS f N ^ 0^PIG F F H M U B X O E kTI M .1 F 481 48: THE DEVELOPMENT OF THE HUMAN BODY. As early as the second month of development the lens vesicle becomes completely inverted by mesodermal tissue in which blood-vessels are developed in considerable num- bers, whence the investment is termed the tunica vascu- Fig. 256. — Posterior (Inner) Surface of the Lens from an Adult SHOWING THE SUTURAL LINES. — (Rabl.) losa lentis (Fig. 264, tv). The arteries of the tunic are in connection principally with the hyaloid artery of the vitreous humor (Fig. 262), and consist of numerous fine branches which envelop the lens and terminate in loops THE OPTIC CUP. 483 almost at the center of its outer surface. This tunic un- dergoes degeneration after the seventh month of develop- ment, by which time the lens has completed its period of most active growth, and, as a rule, completely disappears before birth. Occasionally, however, it may persist to a greater or less extent, the persistence of the portion cover- ing the outer surface of the lens, known as the membrana pupillaris, causing the malformation known as congenital atresia of the pupil. In addition to the vascular tunic, the lens is surrounded by a non-cellular membrane termed the capsule. The origin of this structure is still in doubt, some observers maintaining that it is a product of the investing meso- derm, while others hold it to be a product of the lens epi- thelium. The Development of the Optic Cup. — When the invagina- tion of the outer wall of the optic bulb is completed, the margins of the resulting cup are opposite the sides of the lens vesicle (Fig. 254), but with the enlargement of the lens and cup the margins of the latter gradually come to lie in front of — that is to say, upon the outer surface of — the lens, forming the boundary of the opening known as the pupil. The lens, consequently, is brought to lie within the mouth of the optic cup, and that portion of the latter which covers the lens takes part in the formation of the iris and the adjacent ciliary body, while its posterior portion gives rise to the retina. The chorioidal fissure normally disappears during the sixth or seventh week of development by a fusion of its lips, and not until this is accomplished does the term cup truly describe the form assumed by the optic bulb after the invagination of its outer wall. In certain cases the lips of the fissure fail to unite perfectly, producing the de- fect of the eye known as coloboma; this may vary in its 484 THE DEVELOPMENT OF THE HUMAN BODY. extent, sometimes affecting both the iris and the retina and forming what is termed coloboma iridis, and at others being confined to the retinal portion of the cup, in which case it is termed coloboma chorioideae. Up to a certain stage the differentiation of the two layers which form the optic cup proceeds along similar lines, in both the ciliary and retinal regions. That layer which represents the original internal portion of the bulb becomes thinner as the cup increases in size, and becomes also the seat of a deposition of dark pigment, whence it may be termed the pigment layer of the cup; while the other layer — that formed by the invagination of the outer portion of the bulb, and which may be termed the retinal layer — remains much thicker (Fig. 254) and in its proxi- mal portions even increases in thickness. Later, however the development of the ciliary and retinal portions of the retinal layers differs, and it will be convenient to consider first the history of the ciliary portion. The Development of the Iris and Ciliary Body. — The first change noticeable in the ciliary portion of the retinal layer is its thinning out, a process which continues until the layer consists, like the pigment layer, of but a single layer of cells (Fig. 257), the transition of which to the thicker retinal portion of the layer is somewhat abrupt and corre- sponds to what is termed the ora serrata in adult anatomy. In embryos of 10.2 cm. the retinal layer throughout its entire extent is readily distinguishable from the pigment layer by the absence in it of all pigmentation, but in older forms this distinction gradually diminishes in the iris re- gion, the retinal layer there acquiring pigment and form- ing the uvea. When the anterior chamber of the eye is formed by the splitting of the mesoderm which has grown in between the superficial ectoderm and the outer surface of the lens, the THE IRIS AND CILIARY BODY. 4 8 S peripheral portions of its posterior (inner) wall are in rela- tion with the ciliary portion of the optic cup and give rise to the stroma of the ciliary body and of the iris (Fig. 257) this latter being continuous with the tunica vasculosa lentis so long as that structure persists (Fig. 264). In embryos of about 14.5 cm. the ciliary portion of the cup I.Str Fig. 257. — Radial Section through the Iris of an Embryo op 19 cm. AE, Pigment layer; CC, ciliary folds; IE, retinal layer; I.Str, iris stroma; Pm, pupillary membrane; Rs, marginal sinus; Sph, sphinc- ter iridis. — (Szili.) becomes thrown into radiating folds (Fig. 257), as if by a too rapid growth, and into the folds lamella? of mesoderm project from the stroma. These folds occur not only throughout the region of the ciliary body, but also extend into the iris region, where, however, they are but tem- porary structures, disappearing entirely by the end of the 486 THE DEVELOPMENT OF THE HUMAN BODY. fifth month. The folds in the region of the corpus ciliare persist and produce the ciliary processes of the adult eye. Embedded in the substance of the iris stroma in the adult are non-striped muscle-fibers, which constitute the sphincter and dilatator iridis. It has long been supposed that these fibers were differentiated from the stroma of the iris, but recent observations have shown that they arise from the cells of the pigment layer of the optic cup, the sphincter appearing near the pupillary border (Fig. 257, sph) while the dilatator is more peripheral. The Development of the Retina. — Throughout the retinal region of the cup the pigment layer, undergoing the same changes as in the ciliary region forms the pigment layer of the retina (Fig. 258, p). The retinal layer increases in thickness and early becomes differentiated into two strata (Fig. 254), a thicker one lying next the pigment layer and containing numerous nuclei, and a thinner one containing no nuclei. The thinner layer, from its position and structure, suggests an homology with the marginal velum of the central nervous system, and probably be- comes converted into the nerve-fiber layer of the adult retina, the axis-cylinder processes of the ganglion cells passing into it on their way to the optic nerve. The thicker layer similarly suggests a comparison with the mantle layer of the cord and brain, and in embryos of 38 mm. it becomes differentiated into two secondary layers (Fig. 258), that nearest the pigment layer (r) consisting of smaller and more deeply staining nuclei, probably representing the rod and cone and bipolar cells of the adult retina, while the inner layer, that nearest the marginal velum, has larger nuclei and is presumably composed of the ganglion cells. Little is as yet known concerning the further differentia- tion of the nervous elements of the human retina, but the THE RETINA. 487 history of some of them has been traced in the cat, in which, as in other mammals, the histogenetic processes take place at a relatively later period than in man. Of the histogenesis of the inner layer the information is rather scant, but it may be stated that the ganglion cells are the earliest of all the elements of the retina to become recog- 00 o 00 o %6V o Fig. 258. — Portion of a Transverse .Section of the Retina of a New-born Rabbit. ch, Chorioid coat ; g, ganglion-cell layer ; r, outer layer of nuclei ; p, pig- ment layer. — (Falchi.) nizable. The rod and cone cells, when first distinguish- able, are unipolar cells (Fig. 259, a and c), their single processes extending outward from the cell-bodies to the external limiting membrane which bounds the outer sur- face of the retinal layer. Even at an early stage the cone cells (a) are distinguishable from the rod cells (c) by their 488 THE DEVELOPMENT OF THE HUMAN BODY. more decided reaction to silver salts, and at first both kinds of cells are scattered throughout the thickness of the layer from which they arise. Later, a fine process grows out from the inner end of each cell, which thus as- sumes a bipolar form (Fig. 259, b and d), and, later still, the cells gradually migrate toward the external limiting Fig. 259. — Diagram showing the Development of the Retinal Elements. a, Cone cell in the unipolar, and b, in the bipolar stage ; c, rod cells in the unipolar, and d, in the bipolar stage ; e, bipolar cells; f and i, ama- crin cells; g, horizontal cells; /*, ganglion cells; k, Miiller's fiber; /, external limiting membrane. — (Kallius, after Cajal.) membrane, beneath which they form a definite layer in the adult. In the mean time there appears opposite the outer end of each cell a rounded eminence projecting from the outer surface of the external limiting membrane into the pigment layer. The eminences over the cone cells are larger than those over the rod cells, and later, as both in- THE OPTIC NERVE. 489 crease in length, they become recognizable by their shape as the rods and cones. The bipolar cells are not easily distinguishable in the early stages of their differentiation from the other cells with which they are mingled, but it is believed that they are represented by cells which are bipolar when the rod and cone cells are still in a unipolar condition (Pig. 259, e). If this identification be correct, then it is noteworthy that at first their outer processes extend as far as the external limiting membrane and must later shorten or fail to elon- gate until their outer ends lie in what is termed the outer granular layer of the retina, where they stand in relation to the inner ends of the rod and cone cell processes. Of the development of the amacrine(/, i) and horizontal cells (g) of the retina little is known. From their position in new-born kittens it seems probable that the. former are derived from cells of the same layer as the ganglion cells, while the horizontal cells may belong to the outer layer. In addition to the various nerve-elements mentioned above, the retina also contains neuroglial elements known as Mutter's fibers (Fig. 259, K), which traverse the entire thickness of the retina. The development of these cells has not yet been thoroughly traced, but they resemble closely the ependymal cells observable in early stages of the spinal cord. The Development of the Optic Nerve. — The observations on the development of the retina have shown very clearly that the great majority of the fibers of the optic nerve are axis-cylinders of the ganglion cells of the retina and grow from these cells along the optic stalk toward the brain. Their embryonic history has been traced most thor- oughly in rat embryos (Robinson), and what follows is based upon what has been observed in that animal. The optic stalk, being an outgrowth from the brain, is at 41 49© THE DEVELOPMENT OF THE HUMAN BODY. first a hollow structure, its cavity communicating with that of the third ventricle at one end and with that of the optic bulb at the other. When the chorioid fissure is de- veloped, it extends, as has already been described, for some distance along the posterior surface of the stalk and has lying in it a portion of the hyaloid artery. Later, when the lips of the fissure fuse, the artery becomes en- closed within the stalk to form the arteria centralis retina of the adult (Fig. 262). By the formation of the fissure the original cavity of the distal portion of the stalk becomes obliterated, and at the same time the ventral and posterior walls of the stalk are brought into continuity with the retinal layer of the optic cup, and so opportunity is given for the passage of the axis-cylinders of the ganglion cells along those walls (Fig. 260). At an early stage a section of the proximal portion of the optic stalk (Fig. 261, A) shows the central cavity surrounded by a number of nu- clei representing the mantle layer, and surrounding these a non-nucleated layer resembling the marginal velum and continuous distally with the similar layer of the retina. When the ganglion cells of the latter begin to send out their axis-cylinder processes, these pass into the retinal marginal velum and converge in this layer toward the bottom of the ciliary fissure, so reaching the ventral wall of the optic stalk, in the velum of which they may be distinguished in rat embryos of 4 mm., and still more Ah Fig. 260. — Diagrammatic Longitudinal Section of the Optic Cup and Stalk passing through the Chorioid Fissure. Ah, Hyaloid artery; L, lens; On, fibers of the optic nerve ; Os, optic stalk ; PI, pigment layer, and R, re tinal layer of the retina. THE OPTIC NERVE. 49 1 clearly in those of 9 mm. (Fig. 261, A). Later, as the fibers become more numerous, they gradually invade the lateral and finally the dorsal walls of the stalk, and, at the same time the mantle cells of the stalk become more scat- tered and assume the form of connective- tissue (neurog- lia) cells, while the original cavity of the stalk is gradu- ally obliterated (Fig. 26 1 , B ) . Finally, the stalk becomes a solid mass of nerve-fibers, among which the altered mantle cells are scattered. / lfc|f y Fig. 261. — Transverse Sections through the Proximal Part op the Optic Stalk op Rat Embryos of (A) 9 mm. and (B) 11 mm. — (Robinson.) From what has been stated above it will be seen that the sensory cells of the eye belong to a somewhat different category from those of the other sense-organs. Embryologically they are a specialized portion of the mantle layer of the medullary canal, whereas in the other organs they are peripheral structures either representing or being associated with representatives of posterior root ganglion cells. Viewed from this standpoint, and taking into consideration the fact that the sensory portion of the retina is formed from the invaginated part of the optic bulb, some light is thrown upon the inverted arrangement of the retinal elements, the rods and cones being directed away from the source of light. The normal relations of the mantle layer and marginal velum are retained in the retina, and the latter 492 THE DEVELOPMENT OF THE HUMAN BODY. serving as a conducting layer for the axis-cylinders of the mantle layer (ganglion) cells, the layer of nerve-fibers becomes inter- posed between the source of light and- the sensory cells. Fur- thermore, it may be pointed out that if the differentiation of the retina be imagined to take place before the closure of the medul- lary canal,^a condition which is indicated in some of the lower vertebrates, — there would be then no inversion of the elements, this peculiarity being due to the conversion of the medullary plate into a tube, and more especially to the fact that the retina develops from the outer wall of the optic cup. In certain reptiles in which an eye is developed in connection with the epi- physial outgrowths of the diencephalon, the retinal portion of this pineal eye is formed from the inner layer of the bulb, and in this case there is no inversion of the elements. A justification of the exclusion of the optic nerve from the category which includes the other cranial nerves has now been presented. For if the retina be regarded as a portion of the central nervous system, it is clear that the nerve is not a nerve at all in the strict sense of that word, but is a tract, confined throughout its entire extent within the central nervous system and comparable to such groups of fibers as the direct cerebellar or fillet tracts of that system. The Development of the Vitreous Humor. — It has already been pointed out (p. 477) that a blood-vessel, the hyaloid artery, accompanied by some mesodermal tissue makes its way into the cavity of the optic cup through the chorioid fissure. On the closure of the fissure the artery becomes enclosed within the optic stalk and appears to penetrate the retina, upon the surface of which its branches ramify. In the embryo the artery does not, however, terminate in these branches as it does in the adult, but is continued on through the cavity of the optic cup (Fig. 262) to reach the lens, around which it sends branches to form the tunica vasculosa lentis. According to some authors, the formation of the vitre- ous humor is closely associated with the development of this artery, the humor being merely a transudate from it, while others have maintained that it is a derivative of the THE VITREOUS HUMOR. 493 mesoderm which accompanies the vessel, and is therefore to be regarded as a peculiar gelatinous form of connective tissue. In the mammalian eye it is difficult to determine the relative merits of these two views, but the fact that in the lower vertebrates — the birds, for example — the vitreous humor forms at a time when the optic cup con- tains neither mesoderm cells nor blood-vessels indicates a probability that neither of them is quite sufficient to ex- plain the observed phenomena. Recently it has been suggested that it is to the retinal cells that one must look Fig. 262. — Reconstruction of a Portion of the Eye of an Embryo of 13.8 MM. ah, Hyaloid artery; ch, chorioid coat; I, lens; r, retina. — (His.) for the formation of the humor (Rabl), and further ob- servations along this line are desirable. Over the surface of the vitreous humor a structureless membrane, known as the hyaloid membrane, is formed, apparently by a condensation of the vitreous humor or as a secretion of the retinal cells, and in the more anterior portions of the humor fibers appear, extending across from the ciliary processes to become continuous with the capsule of the lens (Fig. 263, si). These fibers increase in number in later stages and represent the suspensory liga- ment of the lens {zonula Zinnii), and spaces which occur 494 THE DEVELOPMENT OF THE HUMAN BODY. between the fibers enlarge to produce a cavity traversed by scattered fibers and known as the canal of Petit. After about the third month the portion of the hyaloid artery which traverses the vitreous humor begins to un- dergo degeneration, and during the last month of develop- ment it disappears altogether, the only trace of its exist- ence at birth being a more fluid consistency of the axis of ~ - - " J - — — .. - -■ - •■-. - - . . ■— ' ~-^s - -_ —,~-~ """ ' - ~ :, "i' ~%- -"":--" C J j^fe^ CO mc '.;>^ ■ as- Zz&ip^*%£ i rl s—Sfci&J .' .'• , '.*.' «* _ , . ****■ si Fig. 263. — Transverse Section through the Ciliary Region of a Chick Embryo of Sixteen Days. ac, Anterior chamber of the eye; cj, conjunctiva; co, cornea; i, iris; /, lens ; mc, ciliary muscle ; rl, retinal layer of optic cup ; sf, spaces of Fontana ; si, suspensory ligament of the lens ; v, vitreous humor. — (Angelucci.) the vitreous humor, this more fluid portion representing the space originally occupied by the artery and forming what is termed the hyaloid canal (canal of Cloquet). The Development of the Outer Coat of the Eye, of the Cornea, and of the Anterior Chamber. — Soon after the THE CORNEA. 495 formation of the optic bulb a condensation of the meso- derm cells around it occurs, forming a capsule. Over the inner portions of the optic cup the further differentiation of this capsule is comparatively simple, resulting in the formation of two layers, an inner vascular and an outer denser and fibrous, the former becoming the chorioid coat of the adult eye and the latter the sclerotic. More externally, however, the processes are more complicated. After the lens has separated from the sur- face ectoderm a thin layer of mesoderm grows in between the two structures and later gives place to a layer of homo- geneous substance in which a few cells, more numerous laterally than at the center, are embedded. Still later cells from the adjacent mesenchyme grow into the layer, which increases considerably in thickness, and blood- vessels also grow into that portion of it which is in contact with the outer surface of the lens. At this stage the in- terval between the surface ectoderm and the lens is occu- pied by a solid mass of mesodermal tissue (Fig. 264, co and tv), but as development proceeds, small spaces filled with fluid begin to appear toward the inner portion of the mass (ac), and these, increasing in number and size, eventually fuse together to form a single cavity which divides the mass into an inner and an outer portion. The cavity is the anterior chamber of the eye, and it has served to sepa- rate the cornea (co) from the tunica vasculosa lentis (tv), and, extending laterally in all directions, it also separates from the cornea the mesenchyme which rests upon the marginal portion of the optic cup and constitutes the stroma of the iris. Cells arrange themselves on the cor- neal surface of the cavity to form a continuous endothelial layer, and the mesenchyme which forms the peripheral boundary of the cavity assumes a fibrous character and forms the ligamentum pectinatum iridis, among the fibers 496 THE DEVELOPMENT OF THE HUMAN BODY. of which cavities, known as the spaces of Fontana (Fig. 263, sf ), appear. Beyond the margins of the cavity the corneal tissue is directly continuous with the sclerotic, beneath the margin of which is a distinctly thickened portion of mesenchyme resting upon the ciliary processes and forming the stroma of the ciliary body, as well as etc ec- Fig. 264. — Transverse Section through the Ciliary Region of a Pig Embryo of 23 mm. ac, Anterior chamber of the eye; co, cornea; ec, ectoderm; /, lens; mc, ciliary muscle; p, pigment layer of the optic cup; r, retinal layer; tv, tunica vasculosa lentis. — (Angelucci.) giving rise to the muscle tissue which constitutes the ciliary muscle (Figs. 263 and 264, vie). The ectoderm which covers the outer surface of the eye does not proceed beyond the stage when it consists of several layers of cells, and never develops a stratum cor- neum. In the corneal region it rests directly upon the corneal tissue, which is thickened slightly upon its outer THE EYELIDS. 497 surface to form the membrane of Bowman; more periph- erally, however, a quantity of loose mesodermal tissue lies between it and the outer surface of the sclerotic, and, together with the ectoderm, forms the conjunctiva (Fig. 263, cj). The Development of the Accessory Apparatus of the Eye. — The eyelids make their appearance at an early stage as two folds of skin, one a short distance above and the other below the cornea. The center of the folds is at first occu- pied by indifferent mesodermal tissue, which later be- comes modified to form the connective tissue of the lids and the tarsal cartilage, the muscle tissue probably sec- ondarily growing into the lids as a result of the spreading of the platysma over the face, the orbicularis palpe- brarum apparently being a derivative of that sheet of muscle tissue. At about the beginning of the third month the lids have become sufficiently large to meet one another, where- upon the thickened epithelium which has formed upon their edges unites and the lids fuse together, in which condition they remain until shortly before birth. During the stage of fusion the eyelashes (Fig. 265, h) develop at the edges of the lids, having the same developmental his- tory as ordinary hairs, and from the fused epithelium of each lid there grow upward or downward, as the case may be, into the mesodermic tissue, solid rods of ectoderm, certain of which early give off numerous short lateral processes and become recognizable as the Meibomian glands (m), while others retain the simple cylindrical form and represent the glands of Moll. When the eyelids separate, these solid ingrowths become hollow by a break- ing down of their central cells, just as in the sebaceous and sudoriparous glands of the skin, the Meibomian glands being really modifications of the former glands, while the 42 498 THE DEVELOPMENT OF THE HUMAN BODY. glands of Moll are probably to be regarded as specialized sudoriparous glands. A third fold of skin, in addition to the two which pro- duce the eyelids, is also developed in connection with the eye, forming the plica semilunaris. This is a rudimentary mu Fig. 265. — Section through the Margins of the Fused Eyelids in an Embryo of Six Months. h, eyelash; //, lower lid; m, Meibomian gland; mu, muscle bundle; ul, upper lid. — (Schweigger-Seidl.) third eyelid, representing the nictitating membrane which is fairly well developed in many of the lower mammals and especially well in birds. In man a number of glands develop in its substance, forming a small reddish nodule known as the caruncula lachrymalis. The lachrymal gland is developed at about the third THE LACHRYMAL APPARATUS. 499 month as a number of branching outgrowths of the ecto- derm into the adjacent mesoderm along the outer part of the line where the epithelium of the conjunctiva becomes continuous with that covering the inner surface of the upper eyelid. As in the other epidermal glands, the out- growths and their branches are at first solid, later becom- ing hollow by the degeneration of their axial cells. The lachrymal or nasal duct is developed in connection with the groove which, at an early stage in the develop- ment (Fig. 52), extends from the inner corner of the eye to the olfactory pit and is bounded posteriorly by the maxil- lary process of the first visceral arch. The epithelium lying in the floor of this groove thickens toward the begin- ning of the sixth week to form a solid cord, which sinks into the subjacent mesoderm, though retaining connection with the ectoderm at either end; its upper end is con- tinuous with the ectoderm of the edge of the upper eyelid, while the lower one is united with that of the olfactory pit. Later, the solid cord acquires a lumen, and from its pal- pebral end a bud arises which unites with the ectoderm of the edge of the lower eyelid and produces the lower limb of the lachrymal canal. LITERATURE. A. Angelucci: "Ueber Entwickelung und Bau des vorderen Uvealtractus der Vertebraten," Archiv fur mikrosk. Anat., xix, 1881. B. Baginsky: "Zur Entwickelung der Gehorschnecke,' - Archiv fur mik- rosk. Anat., xxviii, 1886. I. Broman: "Die Entwickelungsgeschichte der Gehorknochelchen beim Menschen," Anat. Hefte, xi, 1898. S. Ramon y Cajal: "Nouvelles contributions a l'6tude histologique de la ratine," Journ. de V Anat. et de la Physiol., xxxii, 1896. J. DISSS: "Die erste Entwickelung der Riechnerven," Anat. Hefte, IX, 1897. J. Graberg: " Beitrage zur Genese des Geschmacksorgans der Menschen," Morphol. Arbeiten, vin, 1898. J. A Hammar: "Zur allgemeinen Morphologie der Schlundspalten des 500 THE DEVELOPMENT OF THE HUMAN BODY. Menschen. Zur Entwickelungsgeschichte des Mittelohrraumes, des ausseren Gehorganges und des Paukenfelles beim Menschen," Anat. Anzeiger, xx, 1901 HeERFORdT: "Studien uber den Muse, dilatator pupillse sammt Angabe von gemeinschaftlicher Kennzeichen einiger Falle epithelialer Mus- culatur," Anat. Hejte, xiv. J. HegetschwEilER : " Die embryologische Entwickelung des Steigbugels," Archiu fur Anat. und Physiol., Anat. Abth., 1898. W. His, Jr. : " Die Entwickelungsgeschichte des Acustico-Facialisgebietes beim Menschen,'' Archiv fur Anat. und Physiol., Anat. Abth., Supple- ment, 1897. V. von Mihalkovicz : " Nasenhohle und Jacobsonsches Organ. Eine morphologische Studie," Anat. Hejte, xi, 1898. C. Rabl: "Ueber den Bau und Entwickelung der Linse," Zeitschrift fur ■wissensch. Zoologie, lxii and ixv, 1898; lxvii, 1899. A. Robinson : ' ' On the Formation and Structure of the Optic Nerve and Its Relation to the Optic Stalk," Journal of Anat. and Physiol., xxx, 1896. SiEbEnmann: "Die ersten Anlagen vom Mittelohrraum und Gehorknoch- elchen des menschlichen Embryo in der 4 bis 6 Woche," Archiv jiir Anat. und Physiol., Anat. Abth., 1894. A. Szili: "Zur Anatomie und Entwickelungsgeschichte der hinteren, Irisschichten, mit besonderer Beriicksichtigung des Musculus sphincter iridis des Menschen," Anat. Anzeiger, xx, 1901. F. Tuckerman: "On the Development of the Taste Organs in Man," Journal of Anat. and Physiol., xxiv, 1889 CHAPTER XVI. POST-NATAL DEVELOPMENT. In the preceding pages attention has been directed principally to the changes which take place in the various organs during the period before birth, for, with a few ex- ceptions, notably that of the liver, the general form and histological peculiarities of the various organs are ac- quired before that epoch. Development does not, how- ever, cease with birth, and a few statements regarding the changes which take place in the interval between birth and maturity will not be out of place, in a work of this kind. The conditions which obtain during embryonic life are so different from those to which the body must later adapt itself, that arrangements, such as those connected with the placental circulation, which are of fundamen- tal importance during the life in utero, become of little or no use, while the relative importance of others is greatly diminished, and these changes react more or less profoundly on all parts of the body. Hence, al- though the post-natal development consists chiefly in the growth of the structures formed during earlier stages, yet the growth is not equally rapid in all parts, and indeed in some organs there may even be a relative decrease in size. That this is true can be seen from the annexed figure (Fig. 266), which represents the body of a child and that of an adult man drawn to the same scale. The greater relative size of the head and upper part of the body in the child is very marked, and the central point of the height of the 501 502 THE DEVELOPMENT OF THE HUMAN BODY. child is situated at about the level of the umbilicus, while in the man it is at the symphysis pubis. This excessive development of the upper portions of the body of the child is largely due to the nature of the blood-supply during fetal life, when, as may be seen by reference to Fig. 152, the blood passing to the head, neck, arms and upper por- Fig. 266 —Child and Man Drawn to the Same Scale. — (Longer, from the "Growth of the Brain," Contemporary Science Series, by permission of Charles Scribner's Sons.) tions of the thorax leaves the aorta before the ductus arteriosus opens into it, and is therefore practically un- mixed with venous blood, while throughout the rest of the body the supply is largely diluted with blood from the right side of the heart. That there is a distinct change in the geometric form of POST-NATAL DEVELOPMENT. S03 the body during growth is also well shown by the follow- ing consideration (Thoma). Taking the average height of a new-born male as 500 mm., and that of a man of thirty years of age as 1686 mm., the height of the body will have increased from birth to adolescence \ 6 -^ = 3.37 times. The child will weigh 3.1 kilos and the man 66.1 kilos, and if the specific gravity of the body with the in- cluded gases be taken in the one case as 0.90 and in the other as 0.93, then the volume of the child's body will be 3.44 liters and that of the man's 71.08 liters, and the in- crease in volume will be —^ = 20.66. If, now, the in- crease in volume had taken place without any alteration in the geometric form of the body, it should be equal to the cube of the increase in height; this, however, is 3.37 s = 38.27, a number well-nigh twice as large as the actual increase. But in addition to these changes, which are largely dependent upon differences in the supply of nutrition, there are others associated with alterations in the general ' metabolism of the body. Up to adult life the construc- tive metabolism or anabolism is in excess of the destruc- tive metabolism or katabolism, but the amount of the excess is much greater during the earlier periods of devel- opment and gradually diminishes as the adult condition is approached. That this is true during intrauterine life is shown by the following figures, compiled by Donaldson : Age in Weeks. Weight in Grams. Age in Weeks. Weight in Grams. (ovum) 0.0006 24 635 4 — 28 1220 8 4 32 1700 12 20 36 2240 16 120 40 (birth) 3250 20 285 So 4 THE DEVELOPMENT OF THE HUMAN BODY. From this table it may be seen that the embryo of eight weeks is six thousand six hundred and sixty-seven times as heavy as the ovum from which it started, and if the increase of growth for each of the succeeding periods of four weeks be represented as percentages, it will be seen that the rate of increase undergoes a rapid diminution after the sixteenth week, and from that on diminishes gradually but less rapidly, the figures being as follows : Periods of Weeks. Percentage Increase. Periods of Weeks. Percentage Increase. 8-12 12-16 16-20 20-24 400 500 137 123 24-28 28-32 32-36 36-40 92 39 32 45 That the sapie is true in a general way of the growth after birth maybe seen from the table on page 505, repre- senting the average weight of the body in English males at different years from birth up to twenty- three (Roberts), and also the percentage rate of increase. Certain interesting peculiarities in post-natal growth become apparent from an examination of this table. For while there is a general diminution in the rate of growth, yet there are marked irregularities, the most noticeable being (1) a rather marked diminution during the eleventh and twelfth years, followed by (2) a rapid acceleration which reaches its maximum at about the sixteenth year and then very rapidly diminishes. These irregularities may be more clearly seen from the following charts, which represent the curves obtained by plotting the annual increase of weight in boys (Chart I) and girls (Chart II). The diminution and acceleration of growth referred to POST-NATAL DEVELOPMENT. 505 above are clearly observable, and it is interesting to note that they occur at earlier periods in girls than in boys, the diminution occurring in girls at the eighth and ninth years and the acceleration reaching its maximum at the thirteenth year. Year. Number of Cases. Weight in Kilograms. Percentage Increase. 451 3.2 1 — (10.8) (238) 2 2 14.7* (36)* 3 41 15.4 4.8* 4 102 16.9 9.7 5 193 18.1 7.1 6 224 20.1 11. 7 246 22.6 12.4 8 820 24.9 10.2 9 1425 27.4 10. 10 1464 30.6 11.5 11 1599 32.6 6.5 12 1786 34.9 7. 13 2443 37.6 7.7 14 2952 41.7 10.9 15 3118 46.6 11.7 16 2235 53.9 15.7 17 2496 59.3 10. 18 2150 62.2 4.9 19 1438 63.4 1.9 20 851 64.9 2.5 21 738 65.7 1.2 22 542 67.0 1.9 23 551 67.0 0. Considering, now, merely the general diminution in the rate of growth which occurs from birth to adult life, it * From a comparison with other similar tables there is little doubt but that the weight given above for the second year is too high to be accepted as a good average. Consequently the percentage increase for the second year is too high and that for the third year too low. It may be mentioned that the weights in the original table are expressed in pounds avoirdupois and have been here converted into kilograms, and further the figures representing the percentage increase have been added. 506 THE DEVELOPMENT OF THE HUMAN BODY. becomes interesting to note to what extent the organs which are more immediately associated with the meta- bolic activities of the body undergo a relative reduction in weight. The most important of these organs is un- I Age J » * 7 8 B IO II 12 13 14- 15 16 17 18 Lbsl6 / \ " 14 s M '» ■-' 1;] ', " 10 i ,> ,1 i \\ ' 8 '/ \ \\ 1 1 » / <\ - / ^p , / ^s - 4 \ ,- ■" &. », ,' ' " ~ J - '• 2 Aoe LbsM " 12 ■• JO ■■ 8 « 6 " # " Z II 2 3 4-5 6 7 8 9 10 11 12 13 14- IS 16 17 18 . \ ^*-^ -1 s v 4< **■ 1 ^U '55v ^ ^>~2 '^ V ^^ " b*3 "^ <±*.t ^ s *-...-- $ X!^/ %,_ Fig. 267.— Curves Showing the Annual Increase in Weight in (I) Boys and (II) Girls. The faint line represents the curve from British statistics, the dotted line that from American (Bowditch), and the heavy line the aver- age of the two. Before the sixth year the data are unreliable. — (Stephenson.) doubtedly the liver, but with it there must also be con- sidered the thyreoid and thymus glands, and probably the suprarenal bodies. In all these organs there is a marked POST-NATAL DEVELOPMENT. S07 diminution in size as compared with the weight of the body, as will be seen from the following table (H. Vier- ordt), 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. Supraren- al Bodies. Spleen. Heart. Kid- neys. Brain. Spinal Cord. 141.7 1819.0 4.85 33.8 8.15 26.9 7.05 7.4 10.6 163.0 23.6 300.6 23.3 305.9 381.0 1430.9 5.5 39.15 PERCENTAGE WEIGHT OF ENTIRE BODY New-born and Adult. Liver. Thy- reoid^ Thy- mus. Supraren- al Bodies. Spleen. Heart. Kid- neys. Brain. Spinal Cord. 4.57 2.75 0.16 0.05 0.26 0.04 0.23 0.01 0.34 0.25 0.76 0.46 0.75 0.46 12.29 2.16 0.18 0.06 On the other hand, the remaining organs, when com- pared with the weight of the body, either show an increase or remain practically the same. ABSOLUTE WEIGHT IN GRAMS. New-born and Adult. Skin and Subcu- taneous Tis- sues. Skeleton. Muscula- ture. S T O M A CH and Intes- tines. Pancreas. Lungs. 611.75 11765.0 425.5 11575.0 776.5 28732.0 65 1364 3.5 97.6 54.1 994.9 5o8 THE DEVELOPMENT OF THE HUMAN BODY. PERCENTAGE OF BODY-WEIGHT. New-born and Adult. Skin and Subcu- taneous Tis- sues. Skeleton. Muscula- ture. Stomach and Intes- tines. Pancreas. Lungs. 19.73 17.77 13.7 17.48 25.05 43.40 2.1 2.06 0.11 0.15 1.75 1.50 From this table it will be seen that the greatest incre- ment of weight is that furnished by the muscles, the per- centage 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 differentiation 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 increase, and in that of the skin and subcutaneous tissue a slight diminution. The latter is readily understood when it is remembered 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 the period under POST-NATAL DEVELOPMENT. SO9 consideration, and attention may be drawn to some of the more important of these changes. In the spinal column one of the most noticeable pecu- liarities observable in the new-born child is the absence of the curves so characteristic of the adult. These curves Fig. 268. — Longitudinal Section through the Sacrum of a New- born Female Child. — (Fehling.) 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 muscles, 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 5io THE DEVELOPMENT OF THE HUMAN BODY. marked in the adult, is but slight in the new-born child, as may be seen from Fig. 268, in which the ventral surfaces of the first and second sacral vertebrae look more ventrally than posteriorly, so that there is no distinct promontory. 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 vertebrae becoming quite different, as may be seen from the following table (Aeby) : LENGTHS OF THE VERTEBRAL REGIONS EXPRESSED AS PERCENTAGES OF THE ENTIRE COLUMN. New-born child, Male 2 years, . " 5 " " 11 " " adult Cervical. Thoracic. 25.6 47.5 23.3 46.7 20.3 45.6 19.7 47.2 22.1 46.6 Lumbar. 26.8 30.0 34.2 33.1 31.-6 The cervical region diminishes in length, while the lum- bar gains, the thoracic remaining approximately the same. It may be noticed, furthermore, that the difference be- tween the two variable regions is greater during youth than in the adult, a condition possibly associated with the general more rapid development of the lower portion of the body made necessary by its imperfect development during fetal life. The difference is due to changes in the vertebrae, the intervertebral disks retaining approxi- mately 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 coni- cal, the base of the cone being below. The difference POST-NATAL DEVELOPMENT. 5 I I depends upon slight differences in the form and articula- tions of the ribs, these being more horizontal in the child and the opening of the thorax directed more directly up- ward than in the adult. As regards the skull, the processes of growth are very complicated. 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 membrane bones which, at 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 details, it may be stated that the principal general changes which the skull under- goes in its post-natal development are (i) a relative elongation of its anterior portion and (2) an increase in the relative height of the superior maxillae. If a line be drawn between the central points of the oc- cipital condyles, it will divide the base of the skull into two portions, which in the child'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 be- hind, 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 corre- sponding increase in the dorso-ventral dimensions of the superior maxillae. These bones, indeed, play a very important part in determining the proportions of the skull at different periods. They are so intimately asso- ciated with the cranial portions of the skull that their 512 THE DEVELOPMENT OF THE HUMAN BODY. increase necessitates a corresponding increase in the ante- rior part of the cranium, and their increase in this direc- tion stands in relation to the development of the teeth, the eight teeth which are developed in each maxilla (in- cluding the premaxilla) in the adult requiring a longer bone than do the five teeth of the primary dentition, these again requiring a greater length when completely devel- oped 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 Fig. 269. — Skull op a New-born Child and of an Adult Man, Drawn to Approximately the Same Scale. — (Henke.) regions (Fig. 269). It has been estimated that the vol- umes of the two portions have a ratio of 8 : 1 in the new- born child, 4: 1 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 superior maxillae. As with the increase in length, the increase now under consideration is, to a certain extent at least, asso- ciated with the development of the teeth, these structures calling into existence the alveolar processes which are practically wanting in the child at birth. But a more POST-NATAL DEVELOPMENT. 513 important factor is the development in the maxillae of the antra of Highmore, the practically solid bodies of the bones becoming transformed 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 con- siderable strain to which they would otherwise be sub- jected. These changes in the proportions of the skull have, of course, much to do with the changes in the general pro- portions of the face. But the changes which take place in the mandible are also important 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 develop- ment of the teeth of the primary dentition, and later of the three molars, necessitates an elongation of the hori- zontal ramus equivalent to that occurring in the maxillae, and, at the same time, the separation of the alveolar bor- ders of the two bones requires an elongation of the vertical ramus if the condyle is to preserve its contact with the glenoid fossa, and this, again, demands a diminution 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 epiphysial centers play an important part in the ossifica- tion, and in few are these centers developed prior to birth, while the union of the epiphyses to the main por- tions of the bones takes place only toward maturity. 43 Si4 THE DEVELOPMENT OF THE HUMAN BODY. The dates at which the various primary and secondary centers appear, and the time at which they unite, may be seen from the following table : UPPER EXTREMITY. Bone. Appearance of Primary Cen- ter. Appearance of Secondary Centers. Fusion of Cen- ters. Clavicle, .... 6th week. (At sternal end) 17th year. 20th year. Scapula, .... ( 2 acromial 15th year. ) Body, 8th week -J 2 on vertebral border 16th [■ 20th year. Coracoid, . . 1st year. year. Head 1st year. J 15th year. "1 Great tuberosity 3d year. Y 20th year. Lesser tuberosity 5th year. i Humerus, .... Sth week. Inner condyle 5th year. Capitellum 3d year. "1 Trochlea 10th year. Y 17th year. Outer condyle 14th year. J Ulna, 8th week. Olecranon 10th year. 16th year. Distal epiphysis 4th year. 18th year. Radius, 8th week. Proximal epiphysis 5th year. 17 th year. Distal epiphysis 2d year. 20th year. Os magnum, . 1st year. Unciform, . . . 2d year. Cuneiform, . . 3d year. Semilunar, . . 4th year. Trapezium, . . 5 th year. Scaphoid, . . . 6th year. Trapezoid, . . . 8th year. Pisiform, .... 12 th year. Metacarpals, . 8th week. 3d year. 20th year. Phalanges, . . 8th-l0th week. 3d-5th years. 17th-18th year. The dates in italics are before birth. POST-NATAL DEVELOPMENT. 515 LOWER EXTREMITY. Bone. Appearance of Primary Cen- Appearance of Secondary Fusion of Cen- ter. Centers. ters. Ilium 3d month. Crest 15 th year. Anterior inferior spine -I 15th year. - 22d year. Ischium, .... 3d-4th month. Tuberosity 15 th year 4th month. Crest 18th year. Patella, Cartilage appears at 4th month, ossification in 3d year. f Head 1st year. 20th year. Great trochanter 4th year. 19th year. 7th week. Lesser trochanter 13 th- 14th year. 18th year. Condyle 9th month. 21st year. Tibia, 8th week. 1 Head end of 9th month. Condyle 9th month. 21st-25th year. 21st year. Distal end 2d year. 18th year. Fibula 8th week. 1 Upper epiphysis 5th year. 21st year. Lower epiphysis 2d year. 20th year. Astragalus, . . 1th month. Calcaneum, . . 6th month. 10th year. 1 6th year. Cuboid, A few days after birth. Scaphoid, . . . 4th year. Cuneiform, . . 1st year. Metatarsals, . 8th week. 3d year. 20th year. Phalanges, . . 8th-Wth week. 4th-8th years. The dates in italics are before birth. So far as actual changes in the form of the appendicular bones are concerned, these are most marked in the case of the lower limb. The ossa innominata alter somewhat in their proportions after birth, a fact which may con- veniently be demonstrated by considering 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 comparison, the antero-posterior (dorso- ventral) and transverse diameters of the child and adult have the following proportions (Fehling) : 5 i6 THE DEVELOPMENT OF THE HUMAN BODY. Diameter. New-born Female. Adult Female. New-born Male. Adult Male. . ( Conjugata vera, o (Transverse, 1.00 1.19 0.96 1.01 0.91 0.83 1.00 1.292 1.19 1.151 1.05 1.154 1.00 1.20 0.91 0.99 0.78 0.84 1.00 1.294 >, ("Antero-posterior, 1.18 (3 (.Transverse, 1.14 ~ f Antero-posterior, O (.Transverse, 1.07 1.153 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 from what obtains in the adult. Furthermore, it is interesting to note that sexual differ- ences in the form of the pelvis are clearly distinguishable at birth; indeed, according to Fehling's observations, they become noticeable during the fourth month of intra- uterine development. 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. 270). 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 tro- chanter and forming the neck of the bone. The acetabu- lum is shallower at birth than in the adult and cannot contain more than half the head of the femur; conse- quently the articular portion of the head is much less extensive than in the adult. POST-NATAL DEVELOPMENT. 517 It is a well-known fact that the new-born child habitu- ally holds the feet with the soles directed toward one an- other, a position only reached in the adult with some difficulty, 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. 107), it being difficult to flex the child's foot beyond a line at right angles with the axis of the leg. These conditions are due appar- ently to the extensor and tibialis muscles being relatively r * Fig. 270. — Longitudinal Sections op the Head of the Femur of (A) New-born Child and (B) a Later Stage of Development. ep, Epiphysial center for the head; /;, head; /.trochanter. — (Henke.) shorter and the opposing muscles relatively longer than in the adult, and with the elongation 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, espe- cially of the astragalus. In the child the articular carti- lage of the trochlear surface of this bone is continued on- ward to a considerable extent upon the neck of the bone, which comes into contact with the tibia in the extreme 5 18 THE DEVELOPMENT OF THE HUMAN BODY. 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 child brings the astragalus in close contact with the inner suface of the os calcis and with the sustentaculum tali; with the alteration of position a growth of these por- tions of the calcaneum occurs, the sustentaculum becom- ing 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 astragalus comes into contact with the outer malleolus, with the result that the articular surface is considerably increased on that portion of the bone. Marked changes in the form of the astragalo-scaphoid articulation also occur, but their con- sideration would lead somewhat further than seems desirable. LITERATURE.- C. Aeby: "Die Altersverschiedeiilieiten der menschlichen Wirbelsaule," Archiv. fur Anat. und Physiol., Anat. Abth., 1879. W. CamerER: " Untersuchungen fiber Massenwachsthum und Langen- wachsthum der Kinder,'' Jahrbuch fur 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 Beziehung zu der beim Erwachsenen," Archiv fur Gynakol., x, 1876. W. HenkE: "Anatomie des Kindersalters," Handbuch der Kinderkrank- heiten (Gerhardt), Tubingen, 1881 C. Hennig: "Das kindliche Becken," Archiv fur Anat. und Physiol., Anat. Abth., 1880. C Huter: "Anatomisehe Studien an den Extremitatengelenken Neuge- borener und Erwachsener," Archiv fur patholog. Anat. und Physiol., xxv, 1862. W. Stephenson: "On the Relation of Weight to Height and the Rate of Growth in Man," The Lancet, n, 1888. R. Thoma : " Untersuchungen fiber die Grosse und das Gewicht der anato- mischen Bestandtheile des menschlichen Korpers," Leipzig, 1882. H. ViErordt: "Anatomisehe, Physiologische und Physikalische Daten und Tabellen," Jena, 1893. H. Welcker: "Untersuchungen fiber Wachsthum und Bau des mensch- lichen Schadels," Leipzig, 1862. INDEX A. After-birth, 159 After-brain, 404 Agger nasi, 199 Allantois, 130, 135 Alveolo-hngual glands, 310 groove, 306 Amitotic division, 24 Amnion, 129 Amniotic cavity, 71 Amphiarthroses, 213 Amphiaster, 22 Annulus of Vieussens, 253 Anterior commissure, 426 Antihelix, 474 Antitragus, 474 Antrum of Highmore, 199 Anus, 298 Aortic arch, 264 bulb, 248 septum, 255 Appendicular skeleton, 181, 206 Archenteron, 65, 296 Archoplasm, 20 Arcuate fibers, 409 Areas of Langhans, 332 Arrectores pilorum, 168 Arteries, 261 allantoidean, 262 anastomotica magna, 276 anterior tibial, 274, 276 aorta, 262 brachiocephalic, 265 branchial, 262 carotid, 263 centralis retinae, 490 cceliac axis, 267 dorsalis indicis, 272 pedis, 274 pollicis, 272 epigastric, 271 external iliac, 275 facial, 263 femoral, 276 hyaloid, 476 Arteries: hypogastric, 268 iliac, 266 inferior mesenteric, 267 innominate, 265 intercostal, 266 internal mammary, 271 internal maxillary, 263 interosseous, 272 lingual, 263 lumbar, 266 median, 272 median sacral, 266 omphalo-mesenteric, 242 peroneal, 276 popliteal, 274 posterior tibial, 276 radial, 272 saphenous, 275 sciatic, 274 subclavian, 265, 266 superior intercostal, 271 mesenteric, 262 vesical, 268 temporal, 263 ulnar, 272 umbilical, 262, 267 vertebral, 271 vitelline, 242 Arytenoid cartilages, 357 Aster, 21 Atresia of duodenum, 325 of pupil, 483 Auditory ganglion, 464 Auerbach, plexus of, 448 Auricular septum, 252 Auriculo-ventricular valves, 258 Axial skeleton, 181 Axis-cylinder, 396 B. Bartholin, glands of, 384 Belly-stalk, 85, 135 Bile-capillaries, 327 5'9 520 INDEX. Bladder, 381 Blastoderm, 59 Blastopore, 65 Blastula, 55 Blood, 242 Blood-islands, 241 Blood-vessels, 240 Body-cavity, 65 Bone, cartilage, 176 development of, 176 growth of, 178 membrane, 176 Bone-marrow, 177 Bones : alisphenoid, 197 atlas, 184 axis 185 basioccipital, 195 carpal, 208 clavicle, 206 coccyx, 188 coracoid, 207 ectethmoid, 197 ethmoid, 197 femur, 211,517 fibula, 211 frontal, 201 humerus, 208 hyoid, 204 ilium, 210 incus, 203, 470, 472 innominate, 210, 515 interparietal, 196 ischium, 210 lachrymal, 201 lingular, 197 malar, 202 malleus, 203, 470, 472 mandible, 204 maxilla, 203 mesethmoid, 198 metacarpal, 209 metatarsal, 212 nasal, 201 occipital, 195 orbitosphenoids, 197 palatine, 203 parietal, 201 patella, 211 phalanges, 209, 212 precoracoid, 214 premaxilla, 203 presphenoid, 197 pubis, 210 radius, 208 Bones : ribs, 183, 185 sacrum, 188, 509 scapula, 207 sphenoid, 196 squamosal, 200 stapes, 204, 470, 472 sternum, 188 supraoccipital, 196 suprasternal, 189 tarsal, 211, 517 temporal, 200 tibia, 211 turbinated, 199 tympanic, 200 ulna, 208 vertebrae, 181, 510 vomer, 198 Bowman, membrane of, 497 Brain, 403 Branchial arch skeleton, 202 clefts, 91, 101 epithelial bodies, 312 fistula, 94 Branchiomeres, 123 Burdach, column of, 403 C. Caecum, 323 Calcar, 423 Calcarine fissure, 423 Callosal fissure, 427 Calloso-marginal fissure, 424 Canalis reuniens, 462 Carotid gland, 448 Cartilage bone, 177 Caruncula lachrymalis, 495 Cauda equina, 401 Cavernous sinus, 277 Cell, 17 Cell-theory, 17 Centrosome, 20 Cerebellum, 410 Cerebral convolutions, 422 cortex, 428 hemispheres, 408, 418 Chin ridge, 105 Chondrocranium, 192, 195 Chorda dorsalis, 115 endoderm, 115 Chordae tendineae, 258 Chorioid coat of eye, 478, 495 plexus, 407, 416, 421 Chorioidal fissure, 421, 476 INDEX. 521 Chorion, 84, 142 frondosum, 145 keve, 145 Chromaffine cells, 392 Chromatin, 20 Chromosomes, 22 reduction of, 32 Ciliary body, 485 ganglion, 444, 448 Circumvallate papillae, 458 Cleft palate, 203 sternum, 190 Clitoris, 385 Cloaca, 296 Cloacal membrane, 297 Cloquet, canal of, 494 Coccygeal ganglion, 452 Cochlea, 462, 467 Ccelom, 65 Collateral eminence, 425 fissure, 425 Coloboma:, 483 Colon, 321 Columnse cornea?, 258 Concrescence, 75 , Conjunctiva, 497 Connective tissue, 174 Cornea, 478, 495 Corniculae laryngis, 357 Corona radiata, 36, 376 Coronary sinus, 252 Corpora albicantia, 417 quadrigemina, 414 Corpus albicans, 40 callosum, 426 luteum, 40 striatum, 420 Corti, organ of, 464 Cotyledons, 145 Cowper, glands of, 384 Cricoid cartilage, 357 Cristae acusticae, 464 Crura cerebri, 413 Cuneiform cartilages, 357 Cutis plate, 122 Cytoplasm, 20 Darwin's tubercle, 475 Decidua reflexa, 152 serotina, 153 vera, 150 Decidual, 128, 147, 159 44 Dendrites, 396 Dental groove, 300 papillae, 300 shelf, 300 Dentate gyrus, 423, 427 Dentine, 304 Dermatome, 122, 164 Diaphragm, 338 Diaphysis, 178 Diarthrosis, 213 Diencephalon, 404, 415 Discus proligerus, 35, 376 Dorsal flexure, 91 zone, 400 Duct of Santorini, 332 of Stenson, 309 of Wharton, 309 of Wirsung, 332 Ductus arteriosus, 264 Botalli, 264 communis choledochus, 325 Cuvieri, 277 ejaculatorius, 377 venosus, 281 Duodenum, 320 Ear, 459 Ebner, glands of, 459 Ectoderm, 64 Embryonic disc, 71 Enamel, 301 Endocardium, 248 Endoderm, 65 Endolymphatic duct, 460 Enveloping layer, 59 Ependymal cells, 395 Epiblast, 64 Epibranchial ganglia, 440 Epidermis, 161 Epididymis, 377 Epiglottis, 356 Epiphyses, 178 Epiphysis cerebri, 415 Episternal cartilages, 189 Epitrichium, 161 Eponychium, 166 Epoophoron, 379 Erythroblasts, 245 Erythrocytes, 241 Erythroplastids, 245 Eustachian tube, 472 valve, 253 522 INDEX. Extrauterine pregnancy, 38 Eye, 476 Eyelids, 497 Fallopian tubes, 379 Fasciculus communis, 436 solitarius, 426 Fenestra ovalis, 469 rotunda, 469 Fertilization of ovum, 47 Fetal circulation, 288 Fifth ventricle, 427 Filum terminate, 401 Fimbria ovarica, 379 Flocculus, 411 Floor-plate, 400 Foliate papillae, 459 Fontana, spaces of, 496 Foramen caecum, 306 incisivum, 300 of Winslow, 343 ovale, 253 Fore-brain, 404 Formatio reticularis, 409 Fornix, 426 Fossa supra tonsillaris, 312 Frontal sinuses, 199 Furcula, 311 G. Gall-bladder, 325 Ganglionated cord, 445 Gartner, canals of, 379 Gastral mesoderm, 67 Gastrula, 64 Geniculate bodies, 417 Genital folds, 384 ridge, 360, 371 swellings, 385 tubercle, 384 Germ cells, 24 plasma, 25 Germinal layers, 64, 78 Giant cells, 247 Giraldes, organ of, 377 Goll, column of, 403 Graafian follicle, 34, 375 Gray rami, 444 Growth of body, 502 Gubernaculum testis, 371 Gynecomastia, 173 Gyrus fornicatus, 424 marginalis, 424 H. Haematopoietic organs, 244 Hair, 167 Harelip, 105 Haversian canals, 180 Head bend, 94 cavities, 120, 440 process, 74, 76 Heart, 248 Helix, 474 Hensen's node, 74 Hermaphroditism, 387 Highmore, antrum of, 199 Hind-brain, 404 Hippocampal fissure, 423 Hippocampus, 423 minor, 423 Holoblastic segmentation, 57 Hyaloid canal, 494 Hydatid of Morgagni, 378 stalked, 381 Hymen, 380 Hyperthelia, 173 Hypertrichosis, 169 Hypoblast, 65 Hypochordal bar, 183 Hypophysis cerebri, 418 Hypospadias, 387 I. Infundibulum, 420 Inguinal canal, 390 Insula, 424 Interarticular cartilages, 214 Intercarotid ganglia, 448 Intermediate cell mass, 119 Intermuscular septa, 182 Intervertebral discs, 184 Intestine, 319 Intraparietal fissure, 424 Iris, 485 Isthmus, 404, 413 Iter, 405 J. Jacobson, organ of, 457 Joints, 212 INDEX. 523 K. Karyokinesis, 24 Karyoplasm, 20 Kidney (see Metanephros), 366 Labia majora, 385 minora, 385 Lachrymal duct, 499 gland, 498 Lamina spiralis, 468 terminalis, 418 Lancisi, striae of, 427 Langhans, areas of, 332 cells of, 145 Lanugo, 168 Larynx, 355 Lateral sinus, 277 thyreoids, 314 Lens, 476, 479 Lenticular ganglion, 444 Leukocytes, 243 Ligaments : broad, 371 capsular, 213 coronary, 340 external lateral, of knee, 22 1 great sacro-sciatic, 221 infraspinous, 184 inguinal, 388 intervertebral, 184 ovarian, 371 pectinatum iridis, 495 round, of liver, 290 spheno-mandibular, 204 subflavan, 184 supraspinous, 184 suspensory, of lens, 493 suspensory, of liver, 340 teres, of ovary, 371 Limbs, 105 Lip ridge, 105 Lips, 299 Liquor amnii, 133 Liver, 325 Lungs, 352 Lunula, 166 Luschka's ganglion, 452 Lymph hearts, 291 nodes, 294 Lymphatics, 291 Lymphocytes, 246, 291 M. Macula acusticse, 464 Mammary glands, 170 Mandibular process, 97 Mantle layer, 395 Marchand, accessory suprarenals of, 391 Mastoid cells, 472 process, 200 Maturation of ovum, 43 Maxillary process, 97 Meatus auditorius externus, 473 Meckel's cartilage, 194 diverticulum, 135, 323 Mediastina, 341 Medulla oblongata, 404 Medullary canal, 114 folds, 86, 112 groove, 112 sheath, 399 Megacaryocytes, 247 Meibomian glands, 497 Meissner, plexus of, 448 Membrana pupillaris, 483 reuniens, 123 tectoria, 465 Membrane bone, 176 Menstruation, 38 Meroblastic segmentation, 57 Mesencephalon, 404, 414 Mesenchyme, 80 Mesenteriole, 347 Mesentery, 342 Mesocardium, 334 Mesocolon, 345 Mesoderm, 65 Mesodermic somites, 89, 118 Mesogastrium, 342 Mesonephros, 363 Mesorchium, 371, 389 Mesothelium, 80 Mesovarium, 371 Metamere, 124 Metanephros, 366 Metencephalon, 404, 410 Metopic suture, 201 Midbrain, 404 Middle commissure, 416 Milk ridge, 170 Mitosis, 24 Moderator bands, 258 Moll, glands of, 497 Monro, foramen of, 420 sulcus of, 415 524 INDEX. Monstrosities, 63 Montgomery's glands, 172 Morgagni, hydatid of, 378 Morula, 59 Mouth cavity, 299 Miillerian duct, 369 Muscle plate, 122 Muscles : biceps femoris, 221 branchiomeric, 225 chondroglossus, 231 ciliary, 496 coccygeus, 225 constrictores pharyngis, 229, 231 cranial, 227 curvator coccygis, 225 digastric, 229 dilatator iridis, 486 dorsal, 223 erector spinas, 220 external rectus, 228 gastrocnemius, 237 geniohyoglossus, 224 geniohyoid, 224 hyoglossus, 224 hyposkeletal, 224 intercostal, 220, 224 laryngeal, 229 latissimus dorsi, 219 levator ani, 225 limb, 231 longus colli, 224 masseter, 229 mylohyoid, 229 obliqui abdominis, 220, 224 occipito-frontalis,. 221, 229 omohyoid, 220 palatoglossus, 231 perineal, 227 peroneus longus, 221 platysma, 229 psoas, 224 pterygoid, 229 pyramidalis, 224 rectus abdominis, 220, 224 scaleni, 224 serrati postici, 221 serratus magnus, 220 skeletal, 218 soleus, 237 sphincter ani, 225 sphincter cloacae, 225 sphincter iridis, 486 stapedius, 229, 470 Muscles : sterno-mastoid, 220, 224, 231 styloglossus, 224 stylohyoid, 229 stylopharyngeus, 229 superior oblique, 227 temporal, 229 tensor palati, 229 tensor tympani, 229, 470 transversus abdominis, 220, 224 trapezius, 220, 224, 231 triangularis sterni, 224 Muscular tissue, 216 Musculi papillares, 258 Myelencephalon, 404, 407 Myelin, 399 Myocardium, 248 Myotome, 122 N. Nail fold, 165 Nails, 164 Nasal duct, 499 fossae, 97 process, 104 Neck bend, 94 depression, 98 Nephrostome, 362 Nephrotome, 120 Nerve roots, 397 Nerves: cranial, 430 hypoglossal, 434 olfactory, 455 optic, 489 recurrent laryngeal, 358 spinal, 429 accessory, 429, 438 spino-occipital, 439 splanchnic, 446 superior laryngeal, 358 Nervous system, 394 Neural arch, 183 ridge, 397 Neurenteric canal, 86, 112 Neuroblasts, 395 Neuroglia, 395 Neuromeres, 440 Neurone theory, 399 Non-sexual reproduction, 25 Notochord, 115 Nuck, canal of, 388 Nucleoli, 20 Nucleus, 19 INDEX. 525 Occipital depression, 98 Odontoblasts, 304 (Esophagus, 317 Olfactory lobes, 427 Olivary body, 409 Omentum, greater, 343, 347 lesser, 343 Oocyte, 43 Optic cup, 476, 483 thalami, 416 Ova serrata, 484 Oval fossa, 90, 103 Osteoblasts, 176 Osteoclasts, 180, 247 Otic ganglion, 444, 448 Otocyst, 460, 476 Ovaries, descent of, 387 Ovary, 374 Ovulation, 37 Ovum, 33, 376 fertilization of, 47 maturation of, 43 segmentation of, 53 Palate, 299 Pancreas, 331 Paradidymis, 377 Paraphysis, 416 Parathyreoids, 314 Parietal cavity, 335 Parieto-occipital fissure, 423 Paroophoron, 379 Parovarium, 379 Parthenogenesis, 25 Penis, 385 Pericardial cavity, 338 Perilymph, 467 Perineal body, 384 Perionyx, 166 Periosteum, 176 Periotic capsule, 192, 200 Peritoneum, 342 Petit, canal of, 494 Petrosal sinus, 277 Pfliiger's cords, 375 Pharyngeal bursa, 312 membrane, 297 tonsil, 311 Pharnyx, 310 Pineal body, 415 Pinna, 474 Pituitary body, 419 Placenta, 155 totalis, 155 praevia, 155 uterina, 155 Pleural cavities, 341 Pleuro-peritoneal cavity, 120, 338 Plica semilunaris, 498 Polar globules, 43 Polycaryocytes, 247 Polymastia, 173 Polyspermy, 49 Post-anal gut, 297 Post-branchial bodies, 316 Post-central fissure, 424 Posterior root ganglia, 397 Precentral fissure, 424 Prepuce, 386 Primitive streak, 67, 68, 74 Processus globularis, 104 Pronephric duct, 361 Pronephros, 361 Pronuclei, 49 Prostate gland, 384 Prostomial mesoderm, 67 Protoplasm, 18 Protovertebra, 118 Pulvinar, 417 Rathke's pouch, 300 Rauber's covering layer, 62 Receptaculum chyli, 293 Recessus parietales, 335 Rectum, 297 Red nucleus, 414 Reil, island of, 424 Restiform body, 410 Rete ovarii, 376 testis, 374 Retina, 486 Rhinencephalon, 428 Rolando, fissure of, 424 Roof-plate, 400 Rosenmiiller, groove of , 3 1 2 organ of, 379 S. Sacral bend, 94 Salivary glands, 309 Santorini, cartilages of, 357 duct of, 332 526 INDEX. Sarcode, 18 Sclerotic coat, 478, 495 Sclerotome, 122 Scrotum, 386 Sebaceous glands, 168 Segmentation nucleus, 49 of ovum, 54 Semicircular canals, 461 Semilunar valves, 259 Seminiferous tubules, 374 Septum lucidum, 426 transversum, 336 Sertoli cells, 30 Sexual reproduction, 25 Sinus pocularis, 379 praecervicalis, 101 terminalis, 241 venosus, 248 Situs inversus viscerum, 63 Skeleton, 181 Skin, 101 Skull, 191, 511 Socia parotidis, 309 Soft commissure, 416 Solar plexus, 446 Sole plate, 165 Solitary fasciculus, 408 Somatic cells, 24 mesoderm, 120 Spermatic cord, 390 Spermatid, 30 Spermatocyte, 30 Spermatogenesis, 29 Spermatogonia, 30 Spermatozoa, 27 Sphenoidal cells, 219 Sphenopalatine ganglion, 444, 448 Spinal cord, 400 Splanchnic mesoderm, 120 Spleen, 349 Stenson's duct, 309 Sternum, cleft, 190 Stomach, 318 Stratum granulosum, 35, 376 Sublingual ganglion, 448 gland, 310 Submaxillary ganglion, 444, 448 gland, 309 Substance islands, 241 Subthalamic region, 417 Sudoriparous glands, 169 Sulcus of Monro, 415 Superfetation, 52 Superior longitudinal sinus, 277 Suprabranchial ganglia, 440 Suprarenal bodies, 390 Suprarenals, accessory, 391 Suture, 212 Sylvian fissure, 424 fossa, 423 Sympathetic system, 441 Synchondrosis, 212 T. Tail filament, 98 Taste, organs of, 458 Teeth, 300 Tegmentum, 413 Telencephalon, 404, 418 Temporal fissures, 424 lobe, 421 Testes, descent of, 388 Testis, 372 Thalamencephalon, 404 Thebesian valve, 253 Thoracic duct, 291 Thymus gland, 315 Thyreo-glossal duct, 314 Thyreoid body, 313 cartilage, 356 Tongue, 305 Tonsils, 312 Touch, organs of, 458 Trachea, 355 Tragus, 474 Trophoblast, 72 Tuber cinereum, 417 Tuberculum impar, 305 Tubuli recti testis, 374 Tunica albuginea, 372 vaginalis, 389 vasculosa lentis, 482 'Tween-brain, 404 Twins, 63 Tympanic cavity, 469 membrane, 474 U. Umbilical cord t 97, 139 Umbilicus, 87 Urachus, 138, 382 Ureter, 366 Urethra, 383 Urinogenital system, 360 Urogenital sinus, 382 Uterus, 379 masculinus, 379 INDEX. 527 Utriculus, 462 Uvea, 484 Vagina, 379 Vaginal process, 388 Vas aberrans, 377 deferens, 377 Veins: anterior tibial, 288 ascending lumbar, 286 azygos, 286 basilic, 287 cardinal, 280 cephalic, 287 emissary, 280 external jugular, 280 facial, 280 hemiazygos, 286 hepatic, 283 inferior cava, 284 innominate, 279 internal jugular, 276 jugulo-cephalic, 288 omphalo-mesenteric, 242, 281 ovarian, 285 portal, 282 renal, 285 sciatic, 288 spermatic, 285 subcardinal, 284 superior cava, 279 suprarenal, 284 umbilical, 281 vitelline, 242 Velum, anterior, 413 interpositum, 416 marginal, 395 posterior, 407 Ventral zone, 400 Ventricle, fourth, 405 lateral, 405 third, 405 Ventricular septum, 254 Vermiform appendix, 324 Vermis, 411 Vernix caseosa, 134, 168 Veru montanum, 380 Vesiculae seminales, 377 Vieussens, annulus of, 253 valve of, 413 Villi, chorionic, 143 intestinal, 324 Vitreous humor, 492 Vocal cords, 356 Vulva, 385 W. Wharton's duct, 309 jelly, 141 White rami, 443 Wirsung's duct, 332 Witch milk, 173 Wolffian body, 361 duct, 361 ridge, 360 Wrisberg, cartilages of, 357 Yolk-sac, 83, 130, 134 Yolk-stalk, 87, 130 Yolk-vesicle, 87 Z. Zona, pellucida, 36 Zonula Zinnii, 493 Zuckerkandl, organs of, 450 MEDICAL BOOKS There have been sold more than 140,000 copies of Gould's Dictionaries See Page 12 P. Blakiston's So*n & Company PUBLISHERS OF MEDICAL AND SCIENTIFIC BOOKS 1012 WALNUT STREET, PHILADELPHIA Montgomery's Gynecology A PRACTICAL TEXT-BOOK A modern comprehensive Text-Book. By Edward E. Montgomery, m.d., Professor of Gynecology in Jefferson Medical College, Philadelphia; Gynecologist to the Jefferson and St. Joseph's Hospitals, etc. 527 Illustrations, many of which are from original sources. 800 pages. Octavo. Cloth, $5.00; Leather, $6.00 *#* This is a systematic modern treatise on Diseases of Women. The author's aim has been to produce a book that will be thorough and practical in every particular. 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It will be found wanting in none of these respects. OERTEL Medical Microscopy NEARLY READY A GUIDE TO DIAGNOSIS, ELEMEN- TARY LABORATORY METHODS, AND MICROSCOPIC TECHNIC By T. E, Oertel, M.D., Professor of Pathology and Clinical Microscopy, Medical Depart- ment, University of Georgia. WITH 120 ILLUSTRATIONS 27 JACOBSON'S Operations of Surgery The Operations of Surgery. By W. H. A. Jacobson, f.r.c.s., Surgeon to Guy's Hospital; Consulting Surgeon Royal Hospital for Children and Women; Member Court of Examiners Royal College of Surgeons; Joint Editor Annals of Sur- gery; and F. J. Steward, f.r.c.s., Assistant Surgeon Guy's Hospital and to the Hospital for Sick Children. Fourth Edition, Revised, En- larged and Improved. 550 Illustrations. Two Volumes, Octavo, 1524 pages. Cloth, $10.00 Sheep, $12.00 PRESS NOTICES OF FORMER EDITIONS " The author proves himself a judicious operator, as shown by his choice of methods and by the emphasis with which he refers to the different dangers and complications which may arise to mar success or jeopardize life." — A'ew York Medical Record. " The important anatomical points are clearly set forth, the conditions indicating or contraindicating operative inter- ference are given, the details of the operations themselves are brought forward prominently, and frequently the after- treatment is considered. Herein is one of the strong points of the book." — New York Medical Journal. 28 The Pocket Cyclopedia, of Medicine and Surgery Full Limp Leather, Round Corners, Gilt Edges, $1.00 With Thumb Index, $1.25 Uniform ivith " Gould's Pocket Dictionary " A concise practical volume of nearly 600 pages, containing a vast amount of infor- mation on all medical subjects, including Diagnosis and Treatment of Disease, with Formulas and Prescriptions, Emer- gencies, Poisons, Drugs and Their Uses, Nursing, Surgical Procedures, Dose List in both English and Metric Systems, etc. By Drs. Gould and Pyle Based upon their large "Cyclopedia of Medicine and Surgery." 0* <£ £ *£* This is a new book which will prove of the greatest value to students. It is to the broad field of general medi- cal information what "Gould's Pocket Dictionary" is to the more special one of definition and pronunciation of words. The articles are concise but thorough, and arranged in shape for quick reference. In no other book can be found so much exact detailed knowledge so conveniently classified, so evenly distributed, so methodically grouped. It is Multum in Parvo. 29 A NEW EDITION Crocker on the Skin The Diseases of the Skin. Their Description, Pathology, Diagnosis, and Treatment, with Special Reference to the Skin Eruptions of Children. By H-. Radcliffe Crocker, m.d. , Physician to the Department of Skin Diseases, Uni- versity College Hospital, London. With new Illustrations. Third Edition, Rewritten and Enlarged NEARLY READY, CLOTH, $5.00 * # * This new edition will easily hold the high position given the previous printings. The author is a member of American, English, French, German, and Italian Dermato- logical Societies, and a recognized authority the world over. STURG1S— MANUAL OF VENEREAL DISEASES By F. R. Sturgis, m.d., Sometime Clinical Professor of Venereal Diseases in the Medical Department of the Uni- versity of the City of New York. Seventh Edition, Revised and in Part Rewritten by the Author and Follen Cabot, M.D., Instructor in Genito-Urinary and Venereal Diseases in the Cornell University , Medical College. l2mo. 216 pages. Cloth, ^1.25 *#* This manual was originally written for students' use, and is as concise and as practical as possible. It pre- sents a careful, condensed description of the commoner forms of venereal diseases which occur in the practice of the general physician, together with the most approved remedies. FOR THE DISSECTING ROOM Holden's Anatomy — Seventh Edition 320 Illustrations A Manual of the Dissections of the Human Body. By John Langton, f.r.c.s. Carefully Revised by A. Hewson, m.d., Demonstrator of Anatomy, Jefferson Medical College, Phila- delphia, etc. 320 Illustrations. Two small compact vol- umes. i2mo. Vol. I. Scalp, Face, Orbit, Neck, Throat, Thorax, Upper Extremity. 435 pages. 153 Illustrations. Oil Cloth, $1.50 Vol. II. Abdomen, Perineum, Lower Extremity, Brain, Eye, Ear, Mammary Gland, Scrotum, Testes. 445 pages. 167 Illustrations. Oil Cloth, JS1.50 Each volume sold separately. Hughes a_nd Keith — Dissections Illustrated A Manual of Dissections by Alfred W. Hughes, m.b., m.r.C.s. (Edin. ), late Professor of Anatomy and Dean of Medical Faculty, King's College, London, etc., and Arthur Keith, M.D., Joint Lecturer on Anatomy, London Hospital Medical College, etc. In three parts. With 527 Colored and other Illustrations. I. Upper and Lower Extremity. 38 Plates, 116 other Illustrations. Cloth, $3.00 II. Abdomen. Thorax. 4 Plates, 149 other Illus- trations. Cloth, $3.00 III. Head, Neck, and Central Nervous System. 16 Plates, 204 other Illustrations. Cloth, #3.00 Each volume sold separately. *** The student will find it of great advantage to have a "Dissector" to supplement his regular text-book on anatomy. These books meet all requirements, and as they can be purchased in parts as wanted, the outlay is small. 31 "ir i rii.rjjj p tj.j-jnijrj: EDGAR'S OBSTETRICS A NEW TEXT -BOOK The Illustrations in Edgar's Ob- stetrics surpass in number, in artistic beauty, and in practical worth those in any book of similar character. They are largely from original sources, are made to a scale, and have been drawn by artists of long experience in this class, of medical work. The Text has been prepared with great care. The author's extensive ex- perience in hospital and private prac- tice and as a teacher, his cosmopolitan knowledge of literature and methods, and an excellent judgment based upon these particularly fit him to prepare what must be a standard work. IN PRESS