Talk:Book - A Laboratory Manual and Text-book of Embryology 10

CHAPTER X

Histogenesis

The primitive cells of the embryo are alike in structure. The protoplasm of each exhibits the fundamental properties of irritability, contractility, reproduction, and metabolism (the absorption, digestion, and assimilation of nutritive substances and the excretion of waste products, processes through which growth and reproduction are made possible). As development proceeds, there is a gradual diflferentiation of the cells into tissues, each tissue being composed of like cells, the structure of which has been adapted to the performance of a certain spedal function. In other words, there is division of labor and adaptation of cell structure to the function which each cell performs. The diflferentiation of tissue cells from the primitive cells of the embryo is known as histogenesis. On page 54 the derivatives of the germ layers are given. We shall take up briefly the histogenesis of the tissues derived from the entoderm, mesoderm, and ectoderm in the order named.

The Histogenesis of the Entodermal Epithelium

The cells of the entoderm are little modified from their primitive structure. From the first they are concerned with the processes of absorption, digestion, 'assimilation, and excretion. They form always epithelial layers, lining the digestive and respiratory canals and the glandular derivatives of these. In the pharynx, esophagus, and trachea the cells are early of columnar form and ciliated. The epithelium of the pharynx and esophagus becomes stratified and the surface layers flatten to form squamous cells. The stratified epithelium is developed from a basal germinal layer like the epidermis of the integument (see p. 294). Throughout the rest of the digestive canal the simple columnar epithelium of the embryo persists. At the free ends of the majority of the cells a cuticular membrane develops. Other cells are converted into unicellular mucous glands or gohlet cells. As outgrowths of the intestinal epithelium, are developed the simple tubular glands of the stomach and intestine, and the liver and pancreas.

In the respiratory tract the entoderm forms at first a simple columnar epithelium. Later, in the trachea and bronchi this is diflferentiated into a pseudo++++stratified, ciliated epithelium. The columnar epithelium of the alveoli and alveolar ducts of the lungs is omverted into the flattened re^Hratory ciitheHum. The development of the thymus and thyreoid ^ands, liver and pancreas has been described in Chapter VII.

Histogenesis of the Mesodermal Tissues

The differentiation of the mesoderm has been described on p. 51, Fig. 53. It ^ves rise to the mesodermal segments, intermediate cell masses, somatic and splanchnic layers, all of which are epitheiia, and to the diffuse mesenckyme. The somatic and splanchnic layers oj the mesoderm fonn on their codomic suifaces a single layer of squamous cells termed the mesothdium. This is the covering layer of the pericard um pleurae peritoneum mesentenes serous layer of the viscera, and lining of the vaginal sac in the scrotum From this mesothelium is derived the spleen and also the epitbeha of the gemtal glands and the Mulleiian ducts.

Fig. 290. — Transverse sectioD of a 4 5 mm hirnian embr> o showing the develi^unent of the ■denrtomM (KoUmann) X about 300

The intern ediate cell masses or nephrotomes are the anlages of the pronephros, mesonephros metanephros and their ducLs fp 195)

The Sclerotomes and Mesenchyme

The cavities of the mesodermal s^ ments become filled with diffuse sp ndle shaped cells denved from the adjacent walls; their med in wills ire next converted into similar tissue and the whole migrates mesall) to\ards the neural tube and notochord, and eventually surrounds these structures (Figs. 290 and 323). This diffuse tissue is mesenckyme (see p. 53) , and that derived from a single mesodermal segment constitutes a sclerotome.

The sclerotomes ultimately are converted into connective tissue, into the vertebrae, and into the basal portion of the cranium. The persisting lateral plate of the mesodermal segment becomes a dermo-niyotome, from which the voluntary muscle is diflferentiated and probably the corium of the integument.

In the head region, cranial to the otocysts, no mesodermal segments are formed, but the primitive mesoderm is converted directly into mesenchyme. Mesenchyme is derived also from the somatic and splanchnic mesoderm and from the primitive streak tissue. From the mesenchyme a number of tissues are developed (see p. 54). The origin of the blood and primitive blood vessels and lymphatics has been described; it remains to trace the development of the supporting tissues (connective tissue, fat, cartilage, and bone) and of the muscle fibers.

The Supporting Tissues

The supporting tissues are peculiar in that during their development from the mesenchyme a fibrous, hyaline, or calcified matrix is formed which becomes greater in amount than the persisting cellular elements of the tissue.

Connective Tissue. — Diflferent views are held as to the differentiation of connective tissue fibers. According to Laguess and Merkel, the fibers arise in an intercellular malrix derived from the cytoplasm of mesenchymal cells. Szily holds that fibers are first formed as processes of epithelial cells and that into this fibrous network mesenchymal cells later migrate. The view generally accepted, that of Fleming, Mall, Spalteholz, and Meves, is that the primitive connective tissue fibers are developed as part of the cell, i. e,y are intracellular in origin.

The mesench)mie is at first compact, the cell nuclei predominating. Soon a syncytium is developed, the cytoplasm increasing in amount and forming an open network. Next the cytoplasm is differentiated into a perinuclear granular endo plasm and an outer distinct hyaline layer of ectoplasm (Fig. 291 ^4) (Mall, Amer. Jour. Anat., vol. 1, 1902). In the ectoplasm fibrils appear, derived from coarse filaments known as chandrioconta (Meves, 1910).

Reticular Tissue. — Fine fibers arise in the ectoplasm of the mesenchymal syncytium. The nuclei and endoplasm persist as reticular cells. According to Mall, reticular fibers differ chemically from white connective tissue fibers.

White Fibrous Connective Tissue. — ^The differentiation of this tissue may be divided into two stages: (1) a prefibrous stage during which the ectoplasm is formed rapidly by the endoplasm of the cells, and fibrils resembling those of reticular tissue appear in the ectoplasm (Fig. 291 A)\ (2) the anastomosing fibers take the form of parallel bimdles and are converted through a chemical change into typical white fibers. The spindle-shaped cells are transformed into the connective tissue cells characteristic of the adult. In tendons, the bundles of „ white fibers are arranged in compact parallel fascicles, in

Fig. 291.— The differentiation of Dm suppwting tisnies (after Mail). X 270. A, White float forming in the corium of a 5 cm. pig embryo; B, elastic fibers foimitig in the syncytium of the umbiljcml cord from a 7 cm. embryo; C, developing cartilage from the occipital bone of a 20 nun. pig embtyo.

^^^^^k areolar tissue they are interwoven to form a meshwork. "S^^^^B The cells of the tendons are compressed between the J "" ^^^^^^ bundles of fibers and this accoimts for their peculiar form and arrangement. In the cornea of the eye the cells retain their processes. The corneal tissue is thus embryonic in character and is without elastic fibers or blood vessels. Elastic Tissue. — With the exception of the cornea and tendon, yellow elastic fibers develop in connection with all white fibrous connective tissue. Like the white fibers they are produced in the ectoplasm of the mesenchymal syncytium (Fig. 291 B). They are developed as single fibers, but may coalesce to form the fenestrated membranes of the arteries. According to Ranvier, elastic fibers are produced by the union of ectoplasmic granules, but this view is not supported by cither Mall or Spaltehols:

Fig. 292.— Developing fat cells, the tat blackened ivith osmic acid (after Ranvier). n., Nucleus; g., fat Klobulcs.

-s. the mesenchymal cells give rise not to fibro++++trete within their cytoplasm droplets of fat which influent (Fig. 292). Finally, a single fat globule tills iis and cytoplasm are pressed to the periphery. The us along the course of the blood vessels in areolar con++++r first during the fourth month.

Cartilage

When described as developing in two ways: (!) The mesen*ase in size and form a compact cellular precartilage. Later the is developed be-Jls from their cyto^93 A). The matrix . case be regarded as flasm of the cartilage ^) According to Mall, mesmal cells give rise first to an ^asm in which fibrillar deNext, the cells increase in and are gradually extruded iitil they lie in the spaces of the ?ctoplasmic matri.\ (Figs. 291 C and 293 B). Simultaneously, the ectoplasm is converted into the hyaline matrix peculiar to cartilage, undergoing both a chemical and structural change. About the cartilage cells the endoplasm produces capsules of hyaline substance.

The interstitial growth of cartilage is due: (1) to the direct production of new hyaline matrix; (2) to the formation of capsules about the cells and their transformation into matrix; (3) to the proliferation of the cartilage cells, which may separate or occur in clusters within a single capsule.

Perichondrai growth also takes place about the periphery of the cartilage and is due to the activity of persisting mesenchymal ccUs, which, with an outer sheath of connective tissue, constitute the perichondrium. When cartilage is replaced by bone the perichondrium becomes the periosteum.

In hyaline cartilage t\ie matrix remains hyaline. In fibro-carliiage the fibrillations of the primitive ectoplasm are converted into white fibers. In diistic cartilage yellow elastic fibers are formed in the hyaline malrix,according to Mall; before the hyaline matrix is ditterenliated, according to Spalteholz. Most of the bones of the skeleton are laid down first in the form of cartilage. Later, this is gradually replaced by the development of bone tissue.

Fic. 293. — Diagrams of the development of c: ■fi from mesenchyma (Lewis and Stiihr). A, Bas upon Studnicka's studies of lish; B, upon Mail's stu< of mammals. Ma., mesenchyma.

Bone is a tissue appearing relatively late in the embryo. There are developed two types, the membrane bones of the (ace and craniutn and the cariilage bones which replace the cartilaginous skeleton. Cartilage bones are not simply cartilage transformed into bone by the deposition of caldiun salts, but represent a new tissue which is developed as the cartilage is destroyed.

Membrane Bone. — The flat bones of the face and skull are not preformed as cartilage. The form of a membrane bone is determined by the development of a

Fig. 294. — Two stages in the development of bone. A, Section through the fronts] bone o( ■ 20 mm. pii; embryo (after Mall). X 270. B, Section through the petiosteiun and bone bmellc ai the mandible of > 65 mm. human fetus. X 325.

periosteal membrane from the mesenchyma. The bone matrix is differentiated within the periosteum from enlarged cells, the osteoblasts (bone formers). Osteoblasts appear in clusters and from their cytoplasm is differentiated a fibrillated ectoplasmic matrix like that which precedes the formation of connective tissue and cartilage (Fig. 294 A). This fibrillated matrix, by a chemical change apparently, is converted into a homogeneous bone matrix, which first takes the form of spicules. Others view the fibrillated matrix as an intercellular product and the bone matrix as an interfibrillar deposit. However this may be, the spicules coalesce, form a network of bony plates, and constitute the bone matrix upon the surfaces of which osteoblasts are arranged in a single layer like the cells of an epithelium (Fig. 294 B). These cells may be cuboidal, columnar, or may flatten out as bone formation ceases. As the matrix of the bone is laid down, osteoblasts become engulfed and form bane cells. The bone cells are lodged in spaces termed lacunce. These are connected by microscopic canals, the canaliculi, in which delicate cell processes course and anastomose with those of neighboring cells.

Fig. 295. — A longitudinal section of the two dislal (ihulangrs from ihv fmg^t of n fivc-nHintlis' hull (dus (Sobolta). X 15. Kit, Cartilage shotrin^ calcification and rcsoriiliun; eK, lutdochniiidml bone; M, marrow caiitj-; pK. periodical bone.

The plates of the spongy membrane bone are formed about blood vessels as centers. As the bone grows at the periphery, the bone matrix is resorbed centrally. At this time large multinucleated cells (43 to 91 /i long) appear upon the surfaces of the bone matrix. These cells are known as osteoclasts (bone destroyers). There is, however, no positive evidence that the osteoclasts are active in dissolving the bone. They may be interpreted also as degenerating, fused osteoblasts (Arey, Anat. Rec, vol. 11, 1917). The cavities in which they are frequently lodged are known as Howskip^s lacunce. The bone lamellae of the central portion of the membrane bone are gradually resorbed and this portion of the bone is of a spongy texture. Some time after birth, compact bone lamellae are laid down by the inner osteoblast cells of the periosteum. In the case of flat bones, compact inner and outer plaies or tables are thus developed with spongy bone between them. The spaces in the spongy bone are filled by derivatives of the mesenchyme: reticular tissue, blood vessels, fat cells, and developing blood cells. These together constitute the red bone marrow. The ossification of membrane bone begins at the middle of the bone and proceeds in all directions from this primary center.

Cartilage Bone

The form of the cartilage bone is determined by the preformed cartilage and its surroimding membrane, the perichondrium (Fig. 296). Bone tissue is developed as in membrane bones, save that the cartilage is first destroyed and the new bone tissue develops (1) in, and (2) about it. In the first case, the process is known as endochondral bone formation. In the second case, it is known as perichondral or periosteal bone formation.

Endochondral Bone Formation

The cartilage cells enlarge, become arranged in characteristic rows, and lime is deposited in the matrix (Fig. 295). The perichondrium becomes the periosteimi. From its inner or osteogenic layer, which is densely celltilar, ingrowths invade and resorb the cartilage and fill the primary marrow cavities. The invading osteogenic tissue gives rise to osteoblasts and bone marrow. By the osteoblasts bone is differentiated directly upon persisting portions of the cartilage. As new bone is developed peripherally, it is resorbed centrally to form large marrow spaces. Eventually, all of the cartilage matrix, and probably the cartilage cells as well, are destroyed.

Perichondral Ossification

Compact bone is developed after birth by the osteogenic layer of the periosteum and thus are produced the periasleal lamdkt. In the ribs this is said to be the only method of ossification. The bone lamellie deposited about a blood vessel are concentricaUy arranged and form the conceniric lamellcB of a Haversian system. The Haversian canal of adult bone is merely the space occupied by a blood vessel.

Growth of Cartilage Bones

In cartilage bones there is no interstitial growth as in cartilage. Most of the cartilage bones have more than one center of ossification and growth is due to ■Cartilage ^^ expansion of the interven++++ing cartilage. Flat bones grow at the periphery; ring like bones, such as the vertebrae, have three primary centers of ossification, between which the cartilage continues to grow (Fig. 296 A). In the case of the numerous long bones of the skeleton, the primitive ossification center forms the shaft or diapkysis (Fig. 296 C-JP). The cartilage at either end of the diaphysis grows n^idly and thus the bone increases in length. Eventually, osteogenic tissue invades these cartilages and new ossification centers, the epiphyses, are formed, one at either end. When the growth of the bone in length is completed, the epiphyses, by the ossification of the intervening cartilage, are united to the diaphysis.

The shaft of the long bones grows in diameter by the peripheral deposition of bone lamellae and the central resorption of the bone. In the larger long bones spong}', or cancellated, bone tissue persists at the ends, but in the middle portion a large medullary, or marrow cavity, is developed. This is filled chiefly with fat cells and constitutes the yellow bone marrow.

Fig. 2%. — Diagrams to show the method of growth of Ay a vertebra; By of sacrum; C-F, of a long bone (the tibia).

Regeneration of Bone

If bone is injured or fractured, new bone is developed by osteoblasts derived either from the periosteum or from the bone marrow. The repair of a fracture is usually preceded, by the formation of cartilage which unites the ends of the bones and is later changed to bone. In adults, the i3eriosteum is regarded as esi3ecially important in the regeneration of bone tissue. Macewen (1912), however, rejects this view.

Joints

In joints of the synarthrosis type in which little movement is allowed the mesenchyma between the ends of the bones differentiates into connective tissue or cartilage. This persists in the adult.

In joints of the diartkrosis type the bones are freely movable. The mesenchyma between the bones develops into an open connective tissue in which a cleft appears, the joint cavity. The cells lining this cavity flatten out and form a more or less continuous layer of epithelium, the synovial membrane. From the connective tissue surrounding the joint cavity are developed the various fibrous ligaments typical of the different joints. Ligaments or tendons apparently coursing through the adult joint cavities represent secondary invasions, which are covered with reflexed synovial membrane, and hence are really external to the cavity.

The Histogenesis of Muscle

The muscular system is composed of muscle fibers which form a tissue in which contractility has become the predominating function. The fibers are of three types : (1) smooth muscle cells found principally in the walls of the viscera and blood vessels; (2) striated skeletal muscle, chiefly attached to the elements of the skeleton and producing voluntary movements; (3) striated cardiac muscle, forming the myocardium of the heart. All three types are derived from the mesoderm. The only exceptions are the smooth muscle of the iris, and the smooth muscle of the sweat glands, which are derived from the ectoderm.

Smooth Muscle in general may be said to arise from the mesenchyme, or from embryonal connective tissue. Its development has been studied by McGill (Intemat. Monatschr. f. Anat. u. Physiol., vol. 24, 1907) in the esophagus of pig embryos. The stellate cells of the mesenchyma enlarge, elongate, and their cytoplasm becomes more abundant. The resulting spindle-shaped cells remain attached to each other by cytoplasmic bridges and develop in the superficial layer of their cytoplasm coarse non-contractile myoglia fibrils (Fig. 297) similar to the primitive fibrillar of connective tissue. The myoglia fibrils may extend from cell to cell, thus connecting them. These fibrils are the products of coalesced granules found within the cytoplasm of the myoblasts. In embryos of 30 nmi. fine myofibrillar are differentiated in the cytoplasm of the myoblasts and give it a longitudinally striated appeuance. The cytoidasmlc prooeaat a ai the muscle cells, the cytoplasmic bridges, later give rise to white connective tissue fibers which envelop the muscle fibers and bind them together. Smooth muscle increases in amotmt: (1) by the formatioQ of new fiben from the mesenchyme (>f the embryo; (2) by the transformation into muscle fibers of interstitial

Fig. 297.— Two sUges in tbe development of Unooth muac:e Bben (after UcGHl). A, fnm the csophainis iif a 13 mm. (ng (X 550); coalescing granule! give rise to ccute myo^ik fibriU. S, ftwn tfa« tso[>hafi;us al a 27 mm. pig (X 850); both coarse myoglia fibrils and fine myofibrils are pttMfiL

cells; (3) by the multiplication of their nuclei by mitosis in the more advanced fetal stages.

Striated Skeletal MiAcIe. — All striated voluntary muscle is derived from the mesoderm, cither from the myotomes of the segments (muscles of the trunk) or from the mcsenchyma (muscles of the head). According to Bardeoi (in Keibel and Mall, vol. 1), after the formation of the sclerotome (Fig. 290), which

Vie.. 298. — StBKcs in the histot^nesis of skeletal muscle (after Godlewski). A, from 13 mm. sheep mbryo; li, homugcneous myofibriU in myoblast from 10 mm. guinea pig embryo; C, myoblast from SJ nm. rabbit tmbryo with longitudinally splitting striated myofibrils.

gi\-e5 rise to skeletal tissue, the remaining portion of the primitive segment constitutes the myolome. All the cells of the myotome give rise to myoblasts. TOlliams (Aracr. Jour. Anat., vol. 11, 1910), working on the mesodermal segments of the chick, finds that only the dorsal and mesial cells are myoblasts. By multiplication they form a mesial myolome, while the lateral cells of the original mesodermal segment j)ersist as a dermatome and give rise only to the connective tissue of the corium (Fig. 323). The dermatome lies lateral to the myotome (Fig. 47) and the two together constitute the dermo-myotome (Williams).

As to the origin of the striated voluntary muscle fibers, there is also a difference of opinion. It is generally believed that the myoblasts elongate, and, by the rej)eated mitotic division of their nuclei, become multinucleated. (Godlewski, however, holds that several myoblasts unite to form a single muscle fiber.) The nuclei lie at first centrally, surrounded by the granular sarcoplasm (Fig. 298 A). The sarcoplasmic granules become arranged in rows and constitute the myofibriUce which increase in number by longitudinal splitting (Fig. 298 B, C). The myofibrillae soon differentiate alternating dark and light bands, due to differences in density, and the individual fibrillae become so grouped that their dark and light bands coincide (Fig. 298 C). During development the muscle fibers increase enormously in size, the nuclei migrate to the surface, and the myofibrillae are arranged in bundles or muscle columns (sarcostyles). The fibrils of each column are said to arise by the longitudinal splitting of single primitive myofibrils.

According to Baldwin (Zeitschr. f. allg. Physiol., vol. 14, 1912), the nucleus and perinuclear sarcoplasm is separated from the rest of the muscle fiber by the sarcolemma. With Ap&thy, he would therefore regard the myofibrillae as a differentiated product of the muscle cells and to be homologized with connective tissue fibers. The extrusion of the muscle cell from the muscle fiber may be compared to the extrusion of cartilage cells from the precartilage matrix, as described by Mall (see p. 287).

During the later stages in the development of striated voluntary muscle there is, according to many observers, an active degeneration of the muscle fibers.

While smooth muscle fibers form a syncytium and the enveloping connective tissue is developed directly from the muscle cells, in the case of striated skeletal muscle each fiber is a multinucleated entity which is bound together with others by connective tissue of independent origin.

Striated Cardiac Muscle. — This is developed from the splanchnic mesoderm which forms both the epicardium and the myocardium (Fig. 255). The cells of the myocardium at first form a syncytium in which myofibrillae develop from chondrioconta, or cytoplasmic granules. The myofibrillae are developed at the periphery of the syncytial strands of cytoplasm and extend long distances in the syncytium. They multiply rapidly and form dark and light bands as in skeletal muscle. The syncytial character of cardiac muscle persists in the adult and the nuclei remain central in position. The intercalated discs y typical of adult cardiac muscle, appear relatively late, just before birth in the guinea pig (Jordan and Steele, 1912).

The Histogenesis of the Ectodermal Derivatives

Besides forming the enamel of the teeth and the salivary glands (cf. p. 161), the ectoderm gives rise: (1) to the epidermis and its derivatives (subcutaneous glands, nails, hair, and the lens and conjunctiva of the eye) ; (2) to the nervous system and sensory epithelia; (3) to parts of certain glands producing internal secretions such as the pituitary body, suprarenal glands, and chromaffin bodies. We shall describe here the histogenesis of the epidermis, the development of its derivatives, and the histogenesis of the nervous tissues, reserving for final chajv ters the development of the nervous organs and the glands formed in part from them.

The Epidermis

The single-layered ectoderm of the early embryo by the division of its cells becomes differentiated into a two-layered epidermis composed of an inner layer of cuboidal or columnar cells, the stratum germinativum, and an outer layer of flattened cells, the cpitrichium or periderm (Fig. 299 A).

The stratum germinativum is the reproducing layer of the epidermis. As development proceeds, its cells by division gradually give rise to new layers above it until the epidermis becomes a many-layered or stratified epithelium. The periderm is always the outermost layer of the epidermis. In embryos of 25 to 121 mm. (C R) the epidermis is typically three-layered, the outer flattened layer forming the periderm, a middle layer of polygonal cells, the intermediate layer, and the inner columnar layer, the stratum germinativum (Fig. 299 B). After the fourth month the epidermis becomes many layered. The inner layers of cells now form the stratum germinativum and arc actively dividing cells imited with each other by cytoplasmic bridges. The outer layers of cells become comified, the cornification of the cells proceeding from the stratum germinativum toward the surface. Thus, next the germinal layer are cells containing keratohyalitiy which constitute the double-layered stralum granulosum. A thicker layer above the stratum granulosum shows cells in which drops of a substance called eleidin are formed. These droplets, which are supposed to represent softened keratohyalin, give these cells a clear appearance when examined unstained. Hence the layer is termed the stratum lurMum. In the outer layers of the epidermis the thickened walls of the cells become cornified and in the cells themselves a fatty substance collects. These layers of cells constitute the stratum corneum. The cells of this layer are also greatly flattened, especially at the surface.

When the hairs develop they do not penetrate the outer periderm layer of the epidermis, but, as they grow out, lift it off (sixth month). Hence this layer is known also as the epitrichium (layer upon the hair). Desquamated epitrichiat and epidermal cells mix with the secretion of the sebaceous glands to form the cheesy vernix caseosa which covers the fetal skin. Pigment granules appear soon after birth in the cells of the stratum germinativum. These granules are probably formed in situ. Negro children are quite light in color at birth, but within six weeks their integument has reached the normal degree of pigmentation.

The derma or corium of the integument is developed from mesenchyme, perhaps from that of the dermatomes (Fig. 323) of the mesodermal segments (p. 292). At about the end of the third month a differentiation into the compact corium proper and the areolar subcutaneous tissue occurs. From the corium papilla project into the stratum germinativum.

Fig. 299.— Sections of the integument from a 6S mm human fetus X 440. j1, Section throuKh tlie integument of the neck siiowing ft two-layeied eptdennis and the beginning of a third intermediate layer; B, section from the Integument of the chin in which three la>Trs are well developed in the e]Mdermis.

Anomalies. — Dermoid cysts, resulting from epidermal inclusions, are not infrequent along the lines of fusion of embryonic structures, e. g., branchial clefts, mid-dorsal and midventral body wall.

The Hair

Hairs are derived from thickenings of the epidermis and begin to develop at the end of the second month on the eyebrows, upper tip, and chin. The hair of the general body integument appears at the beginning of the fourth month.

The first evidence of a hair anlage is the elongation of a cluster of epidermal cells in the inner germinal layer (Fig. 300 ^4). The bases of these cells project into the corium, and, above them, cells of the epidermis are arranged parallel to the surface. The elongated cells continue to grow downward until a cylindrical hair anlage is produced (Fig. 300 B, C). This consists of an outer wall formed of a single layer of columnar cells, continuous with the basal layer of the epidermis. This wall bounds a central mass of irregularly polygonal epidermal cells. About the hair anlage the mesenchyma forms a sheath, and at its base a condensation of mesenchyme produces the anlage of the hair papilla, which projects into the enlarged base of the hair anlage. As development proceeds, the hair anlage grows deeper into the corium and its base enlarges to form the iiair bulb (Fig. 300 C). The hair differentiates from the basal epidermal cells surrounding the hair papilla. These cells give rise to a central core which grows toward the surface,

Fig. 300. — Section thrauKh tbc integument of the face o( a 65 nun. human fetus showing three stages in the early development of the hair. X .UO.

distinct from the peripheral cells which form the outer sheath of the hair (Fig. 301). The central core of cells becomes the inner hair sheath and the shaft of the hair. At the sides of the outer hair sheath two swellings appear on the lower side of the obliquely directed hair anlage. The more superficial of these is the anlage of the sebaceous gland (Fig. 301). The deeper swelling is the "epithelial bed." a region where the cells by rapid division contribute to the growth of the hair follicle.

Superficial to the bulb, the cells of the hair shaft become cornified and differentiated into an outer cuticle, middle cortex, and central medulla. The hair grows at the base and is pushed out through the central ca\'ity of the anlage, the cells of which degenerate. When the hair projects above the surface of the epidermis it breaks and carries with it the epilrichial layer. The mesenchymal tissue which surrounds the hair follicle in the neighborhood of the epithelial bed gives rise to the smooth fibers of the arrector pUi muscle. Pigment granules develop in the basal cells of the hair and give it its characteristic color.

Fig. 301.— Loagitudin&l D through a devel<^ing hair from a fetus (after Stfihr). X 220

'half months' human

The first generation of hairs are short-lived, all except those covering the face being cast off soon after birth. The coarser replacing hairs develop, at least in part, from new follicles. Thereafter hair is shed periodically throughout life.

Sweat Glands

The sweat or sudoriparous glands begin to develop in the fourth month from the epidermis of the finger tips, the palms of the hands, and the soles of the feet. They are formed as solid downgrowths from the epidermis, but differ from hair anlages in having no mesenchymal papillae at their bases. During the sixth month the tubular anlages of the gland begin to coil and in the seventh month their lumina appear. The inner layer of cells forms the gland cells, while the outer cells become transformed into smooth mttscU fibers which here arise from the ectoderm. In the axillary region sweat glands occur which are large and branched.

Mammary Glands

The tubular mammary glands peculiar to mammais are regarded as modified sweat glands. In embryos of 9 mm. (Figs. 94 and 1 18) an ectodermal thickening extends ventrolaterally between the bases of the limb buds on either side. This linear epidermal thickening is the milk line. In the future pectoral region of this line, by the thickening and downgrowth of the epidermis there is formed the [Hipilhi-likc anlagc of the mammary gland (Fig. 302 A). From this epithelial aniage buds appear (B) which elongate and form solid cords 15 to 20 in number, the anlages of the milk duels (C). These branch in the mesenchymal tissue of the corium and eventually produce the alveolar end pieces of the mammary glands. In the region where the milk ducts open on the surface the epidermis is evaginated to form the nipple. The glands enlarge rapidly at puberty and are further augmented during pregnancy, while after parturition they become functionally

stages of development of the human marnnuoGroove limiting glandular

The mammary glands are homologised with sweat glands because their development b similar, anil because in the lowtr mammals iheir structure is the same. Rudimentary mammary glands (of Montgomery), which also resemble sweat glands, occur in the areola about the nijiple. In many mammals numerous pairs of mammary glands are developed along the milk line (pig, dog, etc.) ; in some a pair of glands is developed in the pectoral region (primates, eli^phants) ; in others glands are confined to the inguinal region (sheep, cow, horse). In man svipcrnumcrary mammary glands developed along the milk hnc are of not infrequent occur

THE NAILS The anlages of the nails proper are derived from the epidermis and may be reioguizcd in fetuses of 45 mm. (C R). A nail aniage forms on the dorsum of each tli[;itand extends from the tip of the digit almost to the articulation of the terminal phalanx. At the base of the aniage, that is, proximally, the epidermis is folded inward to form the proximal nail fold (posterior nail fold of the adult) (Fig. 303 C). The nail fold also extends laterally on either side of the nail anlage and forms the lateral nail/old of the adult (A, B).

The material of the nail is developed in the lower layer of the proximal nail fold (C). In certain of the epidermal cells, which according to Bowen represent a modified stratum luddum, there are developed keratin or horn fibrils during the fifth month of fetal life. These appear without the previous formation of keratohyalin granules as is the case in the comification of the stratum comeum. The cells flatten and form the plate-like structure of which the solid substance of the nail is composed. Thus the nail substance is formed in the proximal nail fold as far distad as the outer edge of the lunida (the whitish crescent at the base of the adult nai!). The imderiying epidermis distal to the lunula takes no part in the development of the nail substance. The corium throws its surface of contact with the nail into parallel longitudinal folds which produce the longitudinal ridges of the nail. The naU is pushed toward the tip of the digit by the development of new nail substance in the region of the nail fold. The stratum comeum and the epitrichium of the epidermis for a time completely cover the nail matrix and are termed the eponyckium (Fig. 303 C). Later, this is thrown off, but a portion of the stratum comeum persists during life as the curved fold of epidermis which adheres to the base of the adult nail. During life the nail constantly grows at its base (proximally), is shifted distally over the naU bed, and projects at the tip of the digit.

Fig. 303. — Figures showin); the development of the n&il. A, From a 40 mm. humt B, from a 100 mm. fetus (X 13); C, longitudinal section through the nail anlaf{e of 1 (X 24). (Kollmann.) 1 fetus (X 20): 100 nun. fetus

I'hc nails of man are the homologues of the claws and hoofs of other mammals. During ihc ihir.i monlh thickenings of ihc integument over the distal ends of the metacarpals and mil [I tarsals Ijeiome prominent. These correspond to the louck-pads on the feet of clawed mammals. Similar pads are dcvelofwd on the under sides of the distal phalanges.

The Histogenesis of the Nervous Tissue

The primitive anlage of the nervous system consists of the thickened layer of ecKKicrni along the mid-dorsal line of the embryo. This is the neural plate (Fig. 3(H .1 , B) which is folded to form the iieural groove (Figs. 77 A and 78). The edges

Fio. ,5IM.- Kour setiions showing ihe development of the neural tube in human embryos. A, An early -■mbtjo (Kdbel); B, at 2 mm. (Graf Spee); C, at 2 mm. (Mall); D. at 2.7 mm. {Kollmaon).

of the neural plate come together and form the neural tube (Fig. 304 C, D). The cranial portion of this tube enlarges and is constricted into the three primary vesicles of the brain (Fig. 324). Its caudal portion remains tubular and constitutes llie spinal cord. From the cells of this tube, and the ganglion crest connected with it, are differentiated the nervous tissues, \vith the single exception of the nerve cells and fibers of the olfactory epithelium.

The Differentiation of the Neural Tube

The cells of the neural tube differentiate along two lines. There arc formed: (1) nerve cells and fibers, in which irritability and conductivity have become the predominant functions; (2) nettroglia cells and fibers which constitute the supporting or skeletal tissue peculiar to the nervous system. The differeDtiation of these tissues has been studied by Hardesty in pig embryos (Amer, Jour. Anat., vol. 3, 1904). The wall of the neural tube, consisting at first of a single layer of columnar cells, becomes manylayered and finally three zones are differentiated {Fig. 305 A-D). As the wall becomes many-layered the cells lose their sharp outlines and form a compact,

++++Marginal layer Mantle layer Ependymai layer

Marpnol layer 'Ependymai layer Internal limiting membrane

Uetoderm Marginal layer Ependymai layer

1 V 'v'fiU;- i-v^i^!r-^5?js

External limilius mcmb'itnr Manllt laye External limitinf membrane

ng membrane Internal limiting membrane

Mesoderm Marginal layer * Mantle layer Ependymai layer

Fic. J05.—Three stages in the early development of the neural tube showing the origin ol the syncytial framework (after Hardesty). X WO. A, From rabbit before the closure of neural tube; B, from 5 mm. pig after closute of tube; C, from a 7 mm. pig embryo; D, from a 10 mm. pig embryo. *, Boundary between nuclear layer and marginal layer.

cellular syncytium which Is bounded, on its outer and inner surfaces, by an external and internal limiling membrane (B). In a 10 mm. embryo the cellular strands of the syncytium are arranged radially and nearly parallel (Z>). The nuclei are now so grouped that there may be distinguished three layers: (1) an inner ependymai zone with cells abutting on the internal limiting membrane, their processes extending peripherally; (2) a middle mantis or ttudear zotie. and f.1) an outer o marginal zone, non-cellular, into which nerve fibers grow. The cpendymal zone contributes cells for the development of the mantle layer (£>). The cellular mantle layer forms the gray substance of the central ner\'ous system, while the fibrous marginal layer constitutes the while substance if the spinal cord.

The primitive germinal cells of the neural tube divide by mitosis and giw rise to the cpendymal cells of the epcndymal zone and to ifidijferent cells of the mantle layer. From these latter arise spongioblasts and neuroblasts (Fig. 306). The spongioblasts : .u lorm ^ cells and fibers, which form the

supporting tissue of the central n; the neuroblasts are primitive

nerve cells, which, by developing < st^ ire converted into neurones. The

neurones are the structural units of the ne: tissue.

Fig, 306. — Diagrams showing the difTcreDtialion of the cells in the wall of the neural tube and the tl retical derivation of the epcndymal cells, neuroglia cells and neuroblasts (after Schaper).

The Differentiation of the Meuroblasts into Neurones.^The nerve fibers a developed as outgrowths from the neuroblasts, and a nerve cell with all its pro

cesses constitutes a neurone or cellular v. of the nerve fibers as processes of the n^ of the root fibers of the spinal nerves.

The Efferent or Ventral Root Fibers the first month clusters of neuroblasts se^ mt in the mantle layer of the neural tube. The and from the small end of the cell a slender prin and 308). The process becomes the axis i processes may course in the marginal layer nl \ penetrate the marginal layer ventro-latei

)f the nervous system. The ori^nM ts is best seen in the developmelld

e Spinal Nerves. — At the end t

Fig. 307. — ^.Tmuvene sectiau through the spinal cord of a chick embiyo of the third daystiowing neuraxons (F) dtve\ofaag from neuroblasts of the neural tube and from the bipolar ganglion cells, d. B, Neuroblasts from the spinal cord of a seventy-lwo-bour chick. The three to the tight show neuio++++"■"■-" Dne (Cajal).

Fig. 308. — Trans\-erse section of the ^>inal cord from human fetus of Bve weeks showing pearshaped Deuroblasts giving rise to venttml root Gbera (His in Marshall). X 150. NC, Central canal of qiinal cord.

A\>ina\ nrrvMt. SitnnEirly, the cBcrait fibers of the cerebral nerves-grow out fwta UfuriiblastH of the brain wall. Within the cytoplasm of the nerve cells and their [iriniiiry pnKcsscs strands of fine fibrils arc early differentiated. These, the HfUTofihriUit . uri- th« conducting elements of the neurones. The cell bodies of the rrtcn-nt iininincs soon become multipolar by the development of branched semndiiry iinxissL-s, the dtndrUa.

Development of the Spinal Ganglia

After the formation of the neural pitilc tux! ^nM>\i' ii longitudinal ri<lgc of cells appears on each e^de where the ectoderm niul nt'unil plalo arc cimtinuims (Fig. 309 A). This ridge of ectodennal connected at first by bridges of cells which later disappear. In thr hind-brain region certain ganglia of the cerebral ner%-es develop trom the crest but an- ntil segmentally arranged.

The Differentiation of the Afferent Neurones

The cells of the spinal Ranglia differentiate into (1) ganglion cells, and (2) supporting cells, groups which are comparable to the neuroblasts and spongioblasts of the neural tube. The neun»blasts of the ganglia become fusiform and develop a primarj' process at either [xilc; thus these neurones are of the bipolar type {Fig. ii)7 d). The centrally directed processes of the ganglion cells converge and by elongation form the dorsal roots. They penetrate the dorso-lateral wall of the neural tube, bifurcate, and course cranially and caudally in the marginal layer of the spinal cord. By means of branched processes they come in contact with the neurones of the mantle kyer. The peripheral processes of the ganglion cells, as the dorsal spinal roots, join the ventral roots, and, together with them, constitute the trunks of the spinal nerves (Fig. 325).

The Differentiation of the Unipolar Ganglion Cells

At first bipolar, the majority of the ganglion cells become unipolar either by the fusion of the two primar>- processes or by the bifurcation of a single process (Fig. 310). The process of the unipolar ganglion is now T-shaped. Many of the bipolar ganglion cells persist in the adult, while otherii develop several secondary processes and thus become multipolar in form. In addition to forming the ^inal ganglion cells, neuroblasts of tbe ganglion crmi are believed to migrate ventrally and form the sympathetic ganffia (Fig. 325).

The Neurone Theory

The above acaniat of the devdopawDt ot the nnvt 6l>w» {• tbe one generally accepted at the present time. It ucunm that the axi* cylinHer* of all oer^e fibcn are formed a> outgrowths, each from a nd^c cell, an faypolbetu firu prumulfaied by His. The embryological evidence is supported by cxperimenl. It hat Luiif ijixa kiitiwa from tbe work of Waller that if nerves are severed, tbe &ben difit^ tu ibe puini tA tcttiion, and thus isolated from tbeir nerve cells, will degenerate; also, thai regeneration will l«ke place from tbe central stumps o( cut nerves, tbe fibers of which are still conoe«tcd with tbeir cells. More recently Harrison (Amer. Jour. Anat., vol. 5, 1906), experimenting on amphibian larva', has shown: (1) that no peripheral nerves develop if the neural tube and crest are removed; (2) that isolated ganglion cells growing in clotted lymph will give rise to long axis cylindir i)rocesses in the course of four or five hours.

Fig. 310.— A pwtioQ of a iqrfnsl RsnRlion (row fetus of 44 mm. Colfti method (Cajalj.

A second theory, supported by Schwann, Balfour, Dohrn, and Bethe, assumes that the nerve fibers are in part differentiated from a chain of cells, so that the neurone would represent a nuilticellular, not a unicellular structure. Apilhy and O. Schulze modified this cell-chain theory hy assuming that the nerve fibers differentiate in a syncytium which intervenes between the neural tube and the peripheral end organs. Held further modified this theory by assuming that the f)roximal portions of the nerve fibers are derived from the neuroblasts and ganglion cells and that these grow into a syncytium which by differentiation gives rise to the I)eripheral portion of the fiber.

The Differentiation of the Supporting Cells of the Ganglia and Neural Tube

The supporting cells of the spinal ganglia at first form a syncytium in the meshes of which are found the neuroblasts. They differentiate (1) into flattened capsule cells which form capsules about the ganglion cells, and (2) into sheath cells which cnsheath the axis cylinder processes and are continuous with the capsules of the ganglion. It is probable that many of the sheath cells migrate peripherally along with the develoi)ing nerve libers (Harrison). They are at first spindleshaped, and, as primary sheaths, enclose bundles of nerve fibers. Later, by the proliferation of the sheath cells, the bundles are separated into single fibers, each with its sheath (of Schwann), or neurilemma. Each sheath cell forms a segment of the neurilemma, the limits of contiguous sheath cells being indicated by constrictions, the nodes of Ranvier.

The Myelin or Medullary Sheath

During the fourth month an inner myelin sheath ai)pears about many nerve fibers. This consists of a spongy framework of neurokeratin in the interstices of which a fatty substance, myelin, is deposited. The origin of the myeh'n sheath is in doubt. By some (Ranvier) it is believed to be a differentiation of the neurilemma, the myelin being deposited in the substance of the nucleated sheath cell. By others (Kolliker, Bardeen) the myelin is regarded as a direct or indirect product of the axis cylinder. Its integrity is dependent at least ui^on the nerve cell and axis cylinder, for, when a nerve is cut, the myelin very soon shows degenerative changes. Furthermore, it may form where the sheath is absent.

In the central nervous system there is no distinct neurilemma sheath investing the tibers. Sheath cells are said to be present and most numerous during the period whc*n myelin is developed. Ilardesty derives the sheath cells in the central nervous system of the pig from a portion of the supporting cells, or spongioblasts, of the neural tube, and finds that these cells give rise to the myelin of the fibers.

Those fibers which are first functional receive their myelin sheaths first. The myelination of nerve fibers is only completed between the second and third year (Westphal). Many of the peripheral fibers, especially those of the sympathetic system, remain unmyelinated and supplied only with a neurilemma sheath. The myelinated fibers, those with a myelin sheath, have a glistening white appearance and give the characteristic color to the whUt substance of the central nervous system and to the peripheral nerves. Ranson (Amer. Jour, Anat., vol. 12, 1911) has shown that large numbers of unmyelinated fibers occur in the peripheral nerves and spinal cord of adult mammals and man. Those found in the spinal nerves arise from the small cells of the spinal ganglia.

Fig. 311 — Ependymal cellg from the neural tube of chick embryos. A, of first day; B, of third day. Golgi method (Cajal).

The Development of the Supporting Cells. — The spongioblasts of the neural tube (p. 302) difi'erentiate into the supporting tissue of the central nervous system. This includes the ependymal ceUs, which line the neural cavity, forming one of the primary layers of the neural tube, and neuroglia cdls and \hsa fibers.

We have described how the strands of the syncytiimi formed by the spongioblasts become arranged radially in the neural tube of early embryos (Fig. 305 D). As the wall of the neural tube thickens, the strands elongate pari passu and form a radiating branched framework (Fig. 302). The group of spongioblasts which line the neural cavity constitutes the ependymal layer. Processes from these cells radiate and extend through the whole thickness of the neural tube to its l)iTiphcTy. The cell bodies are columnar and persist as the lining of the central canal and ventricles of the spinal cord and brain (Fig. 312).

Xear the median line of the spinal cord, both dorsally and ventrally, the suppiiriing tissue retains its primitive ependymal structure in the adult. Elsewhere the supporting framework is differentiated into neuroglia cells and fibers. The neuroglia cells form part of the spongiublastic syncytium and are scattered through the mantle and marginal layers of the neural tube. By proliferation

Fig. .112. — Ependymal cells or Ihc lumbar corJ from a human fetus of 44 mm. (GoIk! method, Cajal). .1. Floor plate; B, central ranal; C, line of future fusion of walls of neural ca\it,v; E, ependymal cells; *, neurof;lia cells and fibers.

lhf\- increase in number and their form depends upon the pressure of the nerve tells and fibers which develop around them.

SatrogUa fibers arc differentiated (in a manner comparable to the formation of connective tissue fibers, Fig. 291) from the cytoplasm and cytoplasmic processes of the neuroglia cells, and, as the latter primarily form a syncytium, the neuro}rlia fibers may extend from cell to cell. The neuroglia fibers develop late in fetal life and undergo a chemical transformation into neurokeratin, the same mvelinated substance which is found in the sheaths of medullated fibers.