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Part IV - Histogenesis and Morphogenesis of the Organ Systems[edit] Part IV - Histogenesis and Morphogenesis of the Organ Systems: 12. Structure and Development of the Integumentary System | 13. Structure and Development of the Digestive System | 14. Development of the Respiratory-buoyancy System | 15. The Skeletal System | 16. The Muscular System | 17. The Circulatory System | 18. The Excretory and Reproductive System | 19. The Nervous System | 20. The Development of Coelomic Cavities | 21. The Developing Endocrine Glands and Their Possible Relation to Definitive Body Formation and the Differentiation of Sex

Part IV - Histogenesis and Morphogenesis of the Organ Systems[edit] For definitions of cytogenesis, histogenesis, etc., see Chap. 11; for histogenesis and morphogenesis of the organ systems, see Chaps. 12-21. The events described in Chapters 12-21 occur, to a great extent, during the so-called larval period or period of transition. During this period of development, the basic conditions of the various organ-systems which are present at the end of primitive embryonic body formation are transformed into the structural features characteristic of definitive or adult body form. In other words, during this phase of development, the basic, generalized morphological conditions of the various organ-systems of the embryo are rearranged and transformed into the adult form of the systems. As a result, the body as a whole assumes the definitive or adult form.

Tke Integumentary System

A. Introduction

1. Definition and general structure of the vertebrate integument or skin

2. General functions of the skin

3. Basic structure of the vertebrate skin in the embryo

a. Component parts of the developing integument

b. Origin of the component parts of the early integument

1 ) Origin of the epidermal component

2) Origin of the dermal or mesenchymal component

3) Origin of chromatophores

B. Development of the skin in various vertebrates

1. Fishes

a. Anatomical characteristics of the integument of fishes

b. Development of the skin in the embryo of the shark, Squalus acanthias

1 ) Epidermis

2) Dermis

3) Development of scales and glands

c. Development of the skin in the bony ganoid fish, Lepisosteus (Lepidosteus) osseus

d. Development of the skin in the teleost fish

2. Amphibia

a. Characteristics of the amphibian skin

b. Development of the skin in Necturus maculosus

c. Development of the skin in the frog, Rana pipiens

3. Reptiles

a. Characteristics of the reptilian skin

b. Development of the turtle skin

4. Birds

a. Characteristics of the avian skin

1 ) Kinds of feathers

2) General structure of feathers

a) Pluma or contour feather

b) Plumule or down feather

c) Filoplume or hair feather

d) Distribution of feathers on the body

b. Development of the avian skin

1) Development of the epidermis, dermis, and nestling down feather

2) Development of the contour feather

a) Formation of barbs during the primary or early phase of contour-feather formation

b) Secondary phase of contour-feather formation

c) Formation of the barbules and the feather vane

d) Later development of the feather shaft

3) Formation of the after feather

4) Development of the later down and filoplumous feathers

5. Mammals

a. Characteristics of the mammalian skin

b. Development of the skin

1 ) Development of the skin in general

2) Development of accessory structures associated with the skin

a) Development of the hair

b) Structure of the mature hair and the hair follicle

3) Development of nails, claws, and hoofs

4) Development of horns

5) Development of the skin glands

a) Sebaceous glands

b) Sudoriferous glands

c) Mammary glands

C. Coloration and pigmentation of the vertebrate skin and accessory structures

1. Factors concerned with skin color

2. Color patterns

3. Manner of color-pattern production

a. Role of chromatophores in producing skin-color effects

b. Activities of other substances and structures in producing color effects of the skin

c. Genic control of chromatophoric activity

d. Examples of hormonal control of chromatophoric activity

e. Environmental control of chromatophoric activity

A. Introduction

1. Definition and General Structure of the Vertebrate Integument or Skin

The word integument means a cover. The word applies specifically to the external layer of the body which forms a covering for the underlying structures. The integument also includes the associated structures developed therefrom, such as hair, feathers, scales, claws, hoofs, etc. The latter are important features of the body covering. The skin is continuous with the digestive and urogenital tracts by means of mucocutaneous junctions at the lips, anus, and external genitalia.

The integument is composed of two main parts, an outer epidermis and an underlying corium or dermis. Below the latter is a third layer of connective tissue which connects or binds the corium to the underlying body tissues. This third layer forms the superficial fascia (tela subcutanea or hypodermis). The superficial fascia is continuous with the deep fascia or the connective tissue which overlies muscles, bones, and tendinous structures of the body (fig. 272H).

2. General Functions of the Skin

The integument acts as a barrier between other body tissues and the external environment. Modifications of the integument serve also as an external skeleton or exoskeleton in many vertebrates. In warm-blooded forms, the skin is associated intimately with the regulation of body temperature. The hypodermal portion of the skin often serves to store reserve fatty substances. The presence of fat functions as a buffer against mechanical injury from without, as reserve food, and as an aid in temperature regulation in warm-blooded species. Still another and very important function of the skin is its intimate association with the end organs of the peripheral nervous system by means of which the animal becomes acquainted with changes in the external environment. (See Chap. 19.)

. 3. Basic Structure of the Vertebrate Skin in the Embryo a. Component Parts of the Developing Integument

In all vertebrates, the integument arises from a primitive embryonic integument which at first is composed of the cells of the epidermal tube only, i.e., the primitive epidermis. Later this rudimentary condition is supplemented by a condensation of mesenchymal cells below the epidermis. Following this contribution, the primitive skin is composed of two main cellular layers:

(1) a primitive epidermal (ectodermal) layer of one or two cells in thickness and

(2) an underlying mesenchymal layer.

The former gives origin to the epidermis, while the latter is the fundament of the dermis. A little later, chromatophores or pigment cells, presumably of neural crest origin, wander into the primitive dermis and become a conspicuous feature of this layer. In the development of the vertebrate group as a whole, these two basic layers serve as the basis for the later development of the integument. As a result, these two layers undergo characteristic modifications which enable the skin to fulfill its specific role in the various vertebrate species. The marked differences in later development of these two integumentary components in different vertebrate species are associated with the needs and functions of the skin in the adult form.

b. Origin of the Component Parts of the Early Integument

1) Origin of the Epidermal Component. The epidermal component descends directly from the primitive epidermal (ectodermal) organ-forming area of the late blastula, which, as we have seen, becomes greatly extended during gastrulation and, in the post-gastrular period, is tubulated into the elongated, cylinder-like structure. The primitive epidermal tube thus forms the initial skin or outer protective investment of the developing body.

The wall of the primitive epidermal tube at first may be composed of a single layer of cells of one cell in thickness, as in the shark, chick, pig, opossum, or human (figs. 263A; 269A; 272A). However, in teleost fishes and amphibia, the primitive epidermal tube is composed of two layers of cells. For example, in the sea bass, the wall of the primitive epidermal tube is composed of two layers, the outer layer being thin and made up of much -flattened cells and the lower layer being two cells in thickness (fig. 264A, B). In the anurans and urodeles, the wall of the primitive epidermal tube is composed of two layers, each of one cell in thickness (fig. 267 A, D). The lower layer in the frog, salamander, and teleost often is referred to as the inner ectodermal or nervous layer. It is the germinative layer and thus forms the inner or lower portion of the stratum germinativum of the later epidermis (fig. 267 A, D). The outer layer is densely pigmented and forms the periderm.

In the embryo of the shark, chick, and mammal, the single-layered condition of the primitive epidermal tube soon becomes transformed into a doublelayered condition, the outer layer or periderm being composed of muchflattened cells (figs. 263B; 269B; 272B). In all vertebrates, therefore, the

Fig. 263. Developing skin of Squalus acanthias. (A) Section through differentiating somite and epidermis of 10-mm. embryo. (B) Integument of 34-mm. embryo. (C) Section of skin, showing beginning of scale formation in 60-mm. embryo. (D) Scale development in 145-mm. embryo. (E) Later stage of placoid scale, projecting through epidermal layer of skin.

Fig. 264. Diagrams pertaining to the skin of bony fishes. (A and B after H. V. Wilson: Bull. U. S. Fish Commission, Vol. 9, 1889, reprint, 1891; C after Kingsley: Comp. Anat. of Vertebrates, 1912, P. Blakiston’s Son & Co., Phila.; F from Reed; Am. Nat., 41.) (A) Section of ectoderm (primitive epidermis) of 39-hr. embryo of Serranus

atrarius, the sea bass. (B) Epidermis of sea-bass embryo of 59 hrs. (C) Skin of the lungfish, Protopterus. (D) Integument of teleost fish with special reference to scales. (E) Higher power of epidermal and dermal tissue overlying scale in D. (F) Poison gland along pectoral spine of Schilheodes gyriniis.

primitive epidermal layer of the skin eventually is composed of two simple cellular layers, an outer protective periderm, and a lower, actively proliferating stratum germinativum. It is to be observed further that the periderm in the recently hatched frog embryo possesses ciliated cells (fig. 267H, I). These cilia, as in Arnphioxus (fig. 249B), are used for locomotor purposes, and also function to bathe the surface with fresh currents of water. As such, they probably play a part in external respiration.

The periderm forms a protective covering for the actively dividing and differentiating cells below. In the mammals, the periderm occasionally is called the epitrichium, as it eventually comes to rest upon the developing hair. In Arnphioxus, there is no periderm, and the epidermal tube (epidermis) remains as a single layer of one cell in thickness (fig. 250E, F).

2) Origin of the Dermal or Mesenchymal Component. In Arnphioxus, the thin lateral and ventro-lateral walls of the myotome give origin to the dermatome which comes to lie beneath the epidermal wall. From the dermatome arises the dermis or connective-tissue layer of the skin (fig. 250E, F). The origin of the embryonic dermis in the vertebrate group is more obscure than in Amphioxus, for in the vertebrates its origin varies in different regions of the developing body. Moreover, the origin of the dermal mesenchyme is not the same in all species. For example, in the head region of the frog and other amphibia, the dermal portion of the skin is derived in part from wandering mesenchyme of the head area, at least in the anterior extremity of the head and posteriorly to the otic or ear region, while immediately caudal to this area the mesenchyme of the dermis is derived from the dermatomic portion of the somite, together with mesenchymal contributions of the outer wall of the lateral plate mesoderm. In the trunk region of the body, mesenchyme from the dermatomic portion of the somite wanders off to form the embryonic connective-tissue layer of the skin in the dorso-lateral region of the embryo. In the middorsal region, sclerotomic mesenchyme appears to contribute to the dermal area. However, the dermal layer in the latero-ventral region of the body is derived from mesenchymal cells whose origin is the somatopleural layer of the hypomere (lateral plate mesoderm). The dermal layer in the tail arises from the mesenchyme within the developing end bud (tail bud).

The embryonic dermis in the head region of the chick arises from mesenchyme in the head and pharyngeal areas. In the cervico-truncal region, the dermatome of the somite contributes mesenchyme to the forming dermis on the dorso-lateral portion of the body wall (Engert, ’00; Williams, ’10; fig. 269C), whereas latero-ventrally the mesenchyme of the future dermis springs from the lateral wall of the hypomere. That portion of the developing dermis overlying the neural tube appears to receive contributions from the sclerotomic mesenchyme. The mesenchyme which forms the dermal layer of the skin in the tail descends from the mesoderm of the end bud (tail bud).

In the shark embryo, the origin of the embryonic dermis is similar to that of the amphibia. In the mammalian embryo, a small portion of the dermal tissue may arise from the dermatome; however, the greater part arises in the head and pharyngeal area from the mesenchyme within these areas, in the middorsal region of the trunk from sclerotomic mesenchyme, and in the lateroventral region of the trunk from the outer wall of the lateral plate. In the tail region, the tissue of the dermis derives from tail-bud mesoderm. Bardeen (’00) concluded that the dermatome in pig and man gives origin to muscle tissue. However, Williams (’10) doubted this conclusion. The fact remains that the exact fate of the dermatome or cutis plate of the somite in mammals, and even in the lower vertebrates, is not clear.

3) Origin of Chromatophores. Chromatophores or pigment-bearing cells occur in relation to the epidermis and the dermis. Dermal chromatophores are numerous in vertebrates from man down to the fishes. Pigment also appears in the epidermal cells, hair, feathers, and certain epidermal scales. This pigment is derived from melanoblasts or chromatophores which lie in the basal area of the epidermis or in the zone between the epidermis and the dermis (Dushane, ’44). Experimental embryology strongly suggests that these chromatophores are derived from the neural crest cells which in turn take oilgin from the primitive ectoderm in association with the neural tube at the time of neural tube closure. From the neural crests, the mesenchymal cells, which later give origin to chromatophores, migrate extensively throughout the body and to the skin areas (Dushane, ’43, ’44; Eastlich and Wortham, ’46).

B. Development of the Skin in Various Vertebrates

1. Fishes

a. Anatomical Characteristics of the Integument of Fishes

The epidermal layer of the skin of fishes is soft, relatively thin, and composed of stratified squamous epithelium (figs. 263E; 264E; 265). Cornification of the upper layers is absent in most instances. However, in those fishes which come out of the water and spend considerable time exposed to the air, cornification of the surface cells occurs (Harms, ’29). Unicellular mucous glands are abundant, and multicellular glands also arc present (fig. 264C). A slimy mucous covering overlies the external surface of the epidermis. Poison glands may occur in proximity to protective spines or other areas (fig. 264F).

Fig. 265. Development of phosphorescent organ in Porichthys notatus, (From Greene: J. Morphol., 15.) (A) Rudiment, separating from epidermis. (B) Section of ventral organ of free-swimming larva. (C) Section of fully developed ventral organ.

The dermal layer of fishes is a fibrous structure of considerable thickness. The layer of dermal tissue, immediately below the epidermis, is composed of loosely woven, connective-tissue fibers, copiously supplied with blood vessels, mesenchymal cells, and chromatophores. Below this rather narrow region is a thick layer, containing bundles of fibrous connective tissue. Between the latter and the muscle tissue is a thin, less fibrous, subcutaneous layer (fig. 263E).

Scales are present generally throughout the group and are of dermal origin in most species. However, both layers of the skin contribute to scale formation in the shark and ganoid groups of fishes. Scales are absent in some fishes as, for example, in cyclostomes and certain elasmobranchs, such as Torpedo. In certain teleosts, the scales are minute and are embedded in the skin. This condition is found in the family Anguillidae (eels).

Highly specialized, phosphorescent organs are developed in deep-sea fishes as ingrowths of masses of cells from the epidermis. (Consult Green, 1899.) These epidermal ingrowths (fig. 265 A) separate from the epidermal layer and become embedded within the dermis (fig. 265B, C).

b. Development of the Skin in the Embryo of the Shark, Squalus acanthias

1) Epidermis. In shark embryos up to about the 15-mm. stage, the integument consists of an epidermis composed of one layer of cells, one cell in thickness (fig. 263A). The shapes of these cells may vary, depending upon the area of the body. In some areas, especially the dorso-lateral region of the trunk, they are flattened, while along the middorsum of the embryo they are cuboidal. In the pharyngeal area they arc highly columnar.

By the time the embryo reaches 25 to 35 mm. in length, two layers of cells are indicated in the epidermis, an outer periderm of much-flattened cells and a lower, basal, germinative layer, the stratum germinativum (fig. 263B). The stratum germinativum retains its reproductive capacity throughout life, giving origin to the cells which come to lie external to it. Eventually the epidermis is composed of a layer of cells, several cells in thickness. The outer cells may form a thin squamous layer, covering the external surface (fig. 263D).

2) Dermis. The dermis gradually condenses from loose mesenchymal cells which lie below the stratum germinativum of the epidermis (fig. 263B, C). The dermis gradually increases in thickness and becomes composed of scattered cells, intermingled with connective-tissue fibers. Deeply pigmented chromatophores become a prominent feature of the dermal layer, where they lie immediately below the germinative stratum (fig. 263D, E).

3) Development of Scales and Glands. In the formation of the placoid scale of the shark, masses of mesenchymal cells become aggregated at intervals below the stratum germinativum to form scale papillae (fig. 263C). Each papilla gradually pushes the epidermis outward, especially the basal layer (fig. 263D). The cells of the outer margin of the papilla give origin to odontoblasts or cells which secrete a hard, bone-like substance, resembling the dentine of the teeth of higher vertebrates (fig. 263D). This substance is closely related to bone. The cells of the basal epidermal layer, overlying the dentine-like substance, then form an enamel organ, composed of columnar ameloblasts which produce a hard, enamel-like coating over the outer portion of the conical mass of dentine (fig. 263D). As this scale or “tooth-like” structure increases in size, it gradually pushes the epidermis aside and projects above the surface as a placoid scale (fig. 263E). Some are small, while others are large and spine-like. Many different shapes and sizes of scales are formed in different areas of the body (Saylcs and Hershkowitz, ’37).

As the epidermis increases in thickness, unicellular glands appear within the epidermal layer (fig. 263D). These glands discharge their secretion of mucoid material externally, producing a slimy coating over the surface of the skin. Multicellular glands appear at the bases of the spines which develop at the anterior margins of the dorsal fins and in the epidermis overlying the claspers of the pelvic fins of the male.

c. Development of the Skin in the Bony Ganoid Fish, Lepisosteus (Lepidostcus) osseus

The development of the epidermis and dermis in Lepisosteus is similar to that of the shark embryo. Consideration, therefore, is confined to the development of the characteristic ganoid scale.

In the formation of the ganoid scale of Lepisosteus, a different mechanism is involved than in that of the placoid scale of the shark embryo. Most of the scale is of dermal origin; the epidermal contribution of enamel substance is small and restricted to the outer surface of the spines of the scale (fig. 266D-F).

The scale first appears as a thin calcareous sheet, secreted by the dermal cells in the outer portion of the dermis (fig. 266A). Unlike the formation of dentine in the shark skin, the calcareous material comes to enclose some of the scleroblasts (osteoblasts) or bone-forming cells (fig. 266B). This process continues as the scale increases in mass, and the scleroblasts become distributed as bone cells within the hard, bony substance of the scale. These cells occupy small spaces or lacunae within the bone-like substanee, and small eanals (canaliculi) traverse the hard substance of the scale to unite with similar canals from neighboring, bone-cell cavities (Nickerson, 1893, p. 123).

Spine-like projections (fig. 266F) appear on the surface of the bony scales. These spines are secondarily developed and form in a manner similar to the placoid scale of the elasmobranch fish. That is, a dermal papilla is formed externally to the already-formed dermal scale. This papilla pushes outward into the epidermal layer, and a dentine-like substance appears on its outer surface (fig. 266D). As development of the spine proceeds, this cap of dentine gradually creeps basalward and unites secondarily with the dentine of the

Fig. 266. Formation of the scale in Lepisosteus (Lepidosteus) osseus. (After Nickerson; Bull. Mus. Comp. Zool. at Harvard College, 24.) (A) Section through posterior end

of scale of fish, 150 mm. long. (B) Section through po.sterior end of decalcified scale of fish, 300 mm. long. (C) Section through scale of fish, 300 mm. long. (D) Section showing developing spine. (E) Outlines of .scales viewed from surface. (F) Section of scale spine attached to scale.

scale (fig. 266F). The papillary cells thus become entirely enclosed within the spines of dentine, with the exception of a small canal, leading to the exterior, at the base of the spine (fig. 266F). As the dentine-like spine develops, an enamel-like substance is deposited upon its outer surface by the epidermal cells.

Another characteristic of scale formation in Lepisosteus is the deposition of ganoin upon the outer surface of the scale (fig. 266B, C). This ganoin appears to have many of the characteristics of the enamel. It previously was considered to have been formed by the lower layer of epidermal cells, but Nickerson (1893) concluded that it is of dermal origin. The outer, ganoincovered surface of the scale eventually lies exposed to the exterior in the adult condition and, therefore, is not covered by epidermal tissue.

Much of the external surface of the body of the bony ganoid fish, LepL sosteus osseus (common garpike), is covered with these plate-like scales, and, consequently, the epidermal layer of the skin tends to be pushed aside by this form of scaly armor. In Amia calva the epithelial (epidermal) covering is retained, and cycloid scales, similar to those of teleosts, are developed. The “ganoid” scales of Amia lack ganoin. They protect the head (fig. 316D).

d. Development of the Skin in the Teleost Fish

The early development of the epidermis and dermis in the teleost emdryo resembles that of the shark embryo, and a soft glandular epidermis eventually is formed which overlies a thick, connective-tissue-layered dermis, containing numerous scale pockets, each containing a scale (fig. 264D, E). Consideration is given next to the development of the teleostean scale.

The development of the scale in teleost fishes is a complicated affair (Neave, ’36, ’40). It arises in the superficial area of the dermis in relation to an aggregation of cells. This aggregation of cells forms a dermal pocket or cavity. The latter contains a fluid or gelatinous substance. The scale forms within this cavity. A homogeneous scale rudiment of compact, connective-tissue fibers, the fibrillary plate, is established within the gelatinous substance of the scale pocket. A little later, calcareous or bony platelets are deposited upon this fibrous scale plate. The scale continues to grow at its periphery and, thus, stretches the dermal cavity. At the posterior margins of the scale, the dermal cavity becomes extremely thin. Further growth of the scale posteriorly pushes .the epidermis outward, but the epidermis and the thin dermal cavity wall normally retain their integrity (fig. 264D).

The mature scale consists of a hard fibrous substrate, upon the upper posterior margins of which are embedded calcified plates. These calcified plates fuse together basally as development proceeds. Most of the scale is embedded deeply in the tissue of the dermal or scale pocket. At the anterior, deeply embedded end of the scale, small, hook-like, retaining barbs or teeth develop along the inner margins of the scale which serve to fasten the scale within the pocket (fig. 264D).

2. Amphibia

a. Characteristics of the Amphibian Skin

The amphibian skin is soft, moist, and slimy. It is devoid of scales, with the exception of the Gyrnnophiona which possess patches of small scales embedded within pouches in the dermal layer of the skin (fig. 267J). However, some of the Gyrnnophiona lack scales entirely. Unicellular and multicellular glands of epidermal origin are a prominent feature of the amphibian skin (fig. 267F, G). Specialized poison glands also are present (Noble, ’31, p. 133). Glands are developed in some species which attract the members of the opposite sex during the breeding season. In Cryptobranchus, the epidermal layer may be invaded by capillaries which penetrate almost to the surface of the skin in the region of the respiratory folds, located along the lateral sides of the body (Chap. 14). Cornification of the outer epidermal cells is the rule during later stages of development, in some species more than in others. For example, the development of a cornified layer is characteristic of the skin of toads, whose wart-like structures on the dorsal surface of the body represent areas of considerable cornification. Horny outgrowths of the epidermis are common in certain species.

The dermal layer in general is delicate and characterized by the presence of many pigment cells (chromatophores) of various kinds. The scales within the skin of the Gymnophiona are of dermal origin. In frogs, the dermis is separated from the deeper areas of the body along the dorso-lateral region of the trunk by the presence of large lymph spaces.

Fig. 267. Developing integument of amphibia. (A after Field: Bull. Mus. Comp. Zool. at Harvard College, 21; F after Dawson: J. Morphol., 34; H and 1 after Assheton: Quart. J. Micr. Sc., 38; J from Kingsley, 1925: The Vertebrate Skeleton, Blakiston, Philadelphia, after Sarasins.) (A) Section of skin of frog embryo in neural plate stage. (B) Section of skin of 10-mm. frog embryo. (C) Skin of 34-mm. frog embryo. (D) Skin of Necturus embryo, 6 mm. long. (E) Skin of Necturus embryo, 20 mm. long. (F) Structure of mature skin of Necturus. (G) Structure of skin of Rima pipietis of section through head shortly after metamorpho.sis. (H) Frog embryo, 3 mm. long, showing water streams produced by cilia. (I) Semidiagrammatic figure through suckers of frog embryo, 6 to 7 mm. long. (J) Section of skin of the Gymnophionan, Epicrium.

b. Development of the Skin in Necturus maculosus

The newly formed, epidermal tube of a 6-mm. embryo of Necturus consists of two layers of epidermal cells, an outer periderm and an inner stratum germinativum (fig. 267D). In the ventro-lateral region of the trunk, however, these two layers are flattened greatly and may become so attenuated that only one layer of flattened cells is present. Unicellular glands appear in the head region and represent modifications of cells of the outer ectodermal (peridermal) layer.

In larvae of 18 to 20 mm. in length, the epidermis is 3 to 4 cells in thickness, with the outer layer considerably flattened (fig. 267E). The dermis consists of a mass of mesenchymal cells, with large numbers of chromatophores lying near the epidermis. Chromatophores also lie extensively within the epidermal layer; some even approach the outer periphery. According to Eycleshymer (’06), some of the pigment cells of the epidermis represent modified epithelial cells, while others appear to invade the epidermis from the dermis. Dawson (’20) believed these epidermal pigment cells to be entirely of an epidermal origin in Necturus. Dushane (’43, p. 124) considered the origin of epidermal pigment cells in Amphibia in general to be uncertain but suggested “that these cells also come from the neural crest’’ via the dermal mesenchyme.

Later changes in the developing skin consist in an increase in the number of epithelial cells and in a great increase in the thickness of the dermis, with the formation of bundles of connective-tissue fibers. Associated with these changes, two types of multicellular alveolar glands arise as invaginations into the dermis from the stratum germinativum. One type of gland is the granular or poison gland, and the other is the mucous gland. The latter type is more numerous (fig. 267F). Mixed glands, partly mucous and partly granular, also may appear (Dawson, ’20). Large club-shaped cells or unicellular glands may be observed in the lower epidermal areas, while flattened cornified elements lie upon the outer surface of the epidermis.

The dermis is arranged in three layers as follows:

(a) a thin, outer, compact layer between the lower epidermal cells and the dermal chromatophores,

(b) below this outer compact layer, the intermediate spongy layer, containing some elastic, connective-tissue fibers as well as white fibers, and

(c) below the spongy layer, the inner compact layer.

The chromatophores located in the outer part of the dermal layer are of diflferent kinds (see p. 591).

c. Development of the Skin in the Frog, Rana pipiens

The development of the skin of the common frog resembles closely that of Necturus. The primitive epidermal tube consists of two layers of ectodermal cells, an outer periderm and a lower nervous layer or stratum germinativum (fig. 267A). The cells of the periderm contain pigment granules, and unicellular glands also are present, particularly in the head region. At the 10-mm. stage, the outer, pigmented, peridermal layer begins to flatten, while the stratum germinativum assumes the normal characteristics of the reproductive stratum of the epidermis (fig. 267B). The cells are cuboidal and closely arranged. A condensation of mesenchyme, immediately below the thin epidermal layer, represents the rudiment of the future dermis. Chromatophores are prevalent in the dermal area. In figure 267C are shown the characteristics of the skin of the head area of the 34-mm. tadpole, while figure 267G represents the skin of the head region of the newly metamorphosed frog. In this area of the body, the dermis is compact and dense, but in the dorso-lateral area of the trunk, large lymph spaces are present in the dermis.

3. Reptiles

a. Characteristics of the Reptilian Skin

Most reptiles are land-frequenting animals. The land type of habitat dictates the development of a mechanism which keeps the lower layers of the epidermis soft and moist. The problem of epidermal drying is not encountered to any great extent in the fishes and most amphibia because of the moist conditions under which they live. To circumvent the drying effects imposed upon land-living animals, the outer layers of the skin become cornified. A superficial or outer stratum corneum, therefore, becomes a prominent feature of the epidermis of reptiles, birds, and mammals.

Aside from its role of protecting the lower epidermal layers of cells against loss of moisture, the cornified layer also functions as a protective mechanism against mechanical injury. Foot pads, friction ridges, and all calloused structures are evidence of this function. The cornified stratum represents flattened, dead, epithelial cells, infiltrated with a protein substance, keratin, present abundantly in all horny structures, such as claws, scales, etc.

Both epidermal and dermal layers are thickened considerably in reptiles, while epidermal glands, so prominent in fishes and amphibia, are absent, with the exception of certain specialized regions in the oral and anal areas, between the carapace and plastron of some turtles, and between the scales in certain areas of the skin of crocodiles and alligators.

b. Development of the Turtle Skin

The turtle is an example of an armored animal, possessing a “shell” consisting of a dermal skeleton, the carapace, and the plastron, composed of a

Fig. 268. Development of turtle skin. (A) Section through turtle embryo, showing early division of epidermis into periderm and germinative stratum. (B) Section showing two-layered condition of epidermis in slightly older embryo. (C) Section through dorsal area of embryo, 1 1 mm. long. (D) Higher power drawing of epidermis of 11-mm. embryo. (E) Section of skin of turtle, after hatching, to show horny plates. (F) Higher power sketch of skin shown in square in (E). (G) Section of skin of turtle

just before hatching, showing epidermal scales of carapace, dermal mesenchyme, and vertebrae.

series of interlocking bony paltes, associated with an outer cover, the epidermal skeleton, composed of horny scutes. The latter comprises the so-called tortoise shell of commerce. The dorsal carapace and ventral plastron are united along their lateral edges by a bony ridge, and the carapace is firmly fused with the vertebrae and ribs of the endoskeleton. The skin of the head, neck, tail, and legs is fortified with thick horny plates placed at intervals (fig. 268E). Between these horny plates, the stratum corneum is highly developed (fig. 268F).

At the 11- to 15-mm. stage, the condensation of dermal mesenchyme already is thickened greatly in the dorsal region of the embryo in the future carapace area. This thickened condition and the intimate association of the mesenchyme with the trunk vertebrae and ribs are shown in figure 268C. The rudiment of the plastron begins to appear in the ventral region at this time.

After the young hatch from the egg, ossifications occur within the dermal mesenchyme of the carapace and plastron. The bony ossifications of the carapace gradually fuse with the flattened trunk vertebrae and the flattened ribs. In figure 268G is shown a longitudinal section through a part of the middorsal area of a turtle just before hatching. It is to be observed that the epidermal horny scales or scutes are well formed, while the dermal mesenchyme of the carapace is wrapped intimately around the flattened, dorsal, spinous processes of the vertebrae.

Epidermal scales and thickened horny skin pads, together with an armor of bone, in turtles, demonstrate the types of dermal and epidermal differentiations which form a protective coat in the reptilian group. The “shed skin” of the snake represents a sheet of horny epidermal scales which is periodically cast off. New scales are reformed repeatedly throughout the life of snakes. The rattles on the terminal end of the tail in the rattlesnake represent horny rings, developed proximal to the horny spine, prevalent as the end piece of the tail of many serpents. Lizards are well protected with thick epidermal scales, and in some species these scales are reinforced with dermal bony plates. The crocodiles are tough-skinned animals, possessing thick epidermal scales; the dorsal scales are supported underneath by corresponding dermal bony plates. Horny claws develop upon the digits of the appendages ^n turtles, crocodiles, and lizards.

Fig. 269. Development of skin in the chick. (C after Williams: Am. I. Anat., 11.) (A) Epidermis of 48-hr. chick. (B) Epidermis of 72-hr. chick. (C) Dermal mesenchyme, arising from dermatome of embryo of 40 somites. (D) Skin of chick embryo, incubation six days. (E) Skin of eight-day embryo, showing beginning of feather rudiment. (F) Eleven-day embryo, feather rudiment. (G) Section of mature skin between feather outgrowths. Observe that the epidermis is thin, and that the dermis is composed of two compact layers separated by a vascular layer.

4. Birds

a. Characteristics of the Avian Skin

The skin of the bird is more delicate than that of the reptile. The epidermal layer is thin with a highly cornified external surface. The dermis is composed of an outer compact layer below the epidermis, and beneath the latter is a vascular layer. Below the vascular layer is another compact layer of connective-tissue fibers, and between this layer and the deep fascia is the characteristic adipose (fatty) layer (fig. 269G). Extensive cutaneous glands are not developed. However, the two uropygial or preening glands at the base of the tail are common to most birds, although they are not present in the ostriches. In certain gallinaceous birds, such as the common fowl, modified sebaceous glands are present around the ear. Scales, resembling the reptilian type, are developed on the distal parts of the legs, while feathers present a feature characteristic of the avian skin.

1) Kinds of Feathers. Feathers arc of many kinds, but they may be grouped under three major categories:

(1) plumae (plumous or pennaceous feathers), the most perfectly constructed type of feather, filling the role of contour feathers,

(2) plumules (plumulae or plumulaceous feathers), making up the under feather coat or down, and

(3) hloplumes or hair feathers.

Of all the epidermal structures developed in the vertebrate group, feathers appear to be the most ingeniously constructed. They possess to a high degree liic qualities of lightness, strength, and toughness which serve to protect a delicately constructed skin from cold, moisture, and abrasion.

2) General Structure of Feathers: a) Pluma or Contour Feather. The plumous feather consists of a rachis (shaft or scape) and a vane. The proximal portion of the rachis or shaft is the quill or calamus. The latter is hollow but may contain a small amount of loose pith. It has an opening, the inferior umbilicus, at its base. The quill resides in a feather follicle, a deep pit surrounded by epidermal tissue projecting downward into the dermal part of the skin (fig. 270D, E). Above the quill is the expanded “feathery” portion of the feather, called the vane. At the junction of the quill and the vane is a small opening, the superior umbilicus, to which is attached, in some contour feathers, a secondary, smaller shaft, the aftershaft or hyporachis, together with a group of irregularly placed barbs.

The shaft of the vane of the feather is semisolid, with its interior filled with a mass of horny, air-filled cavities. Extending outward from the shaft in this area are lateral branches or barbs (fig. 270E). The barbs form two

Fig. 270. Diagrams of developing feathers in chick. (A) Nestling, down-feather rudiment of chick of about 12 days of incubation. (B) Feather rudiment, 12 to 14 days of incubation, showing beginning of definitive feather rudiment. (C) Nestling down rudiment and definitive feather rudiment of chick shortly before hatching. (D) Relation of nestling down feather to definitive feather shortly after hatching. (E) Later stage in definitive feather development; nestling down feather is attached to distal end of first definitive feather. (F-H) Cross sections of nestling down rudiment diagrammatically shown in (B). (I) Cross section of definitive feather rudiment shown in

(D). (J) Cross section of definitive rudiment shown in (E). It is to be noted that the

sheath around the developing feather extends for a considerable distance beyond the surface of the skin during development. This area is shortened considerably in E for diagrammatic purposes. F-l based on data from Jones (’07).

rows, one on either side of the shaft. From the barbs, smaller branches extend outward; the latter are the barbules (fig. 270E). An interlocking system of hooks, the barbicels, enables the barbule of one barb to connect with a barbule of the next barb. If these interlocking hooks are disrupted mechanically, the bird restores them while preening its feathers.

b) PLUMULfe OR Down Feather. The plumules or down feathers form an inner feathery coat which lies below the contour feathers in the adult bird. They constitute the main insulating portion of the feather coat. In the down feathers of the adult, the barbs arise in bouquet fashion at the distal end of the quill. On the other hand, the nestling or first down feathers of the chick or newly hatched birds of other species do not possess a quill, for the barbs are attached to the distal ends of the apical barbs of the definitive feather (fig. 270E). Therefore, two types of down feathers are found:

( 1 ) the nestling down feather without a quill and

(2) the later down feather which possesses a quill.

The barbules in down feathers do not interlock, and a vane is not formed (fig. 270D, E).

c) Filoplume or Hair Feather. The filoplume or hair feather possesses a long slender shaft which generally is deprived of barbs, although a tuft of barbs may be present at the distal end.

d) Distribution of Feathers on the Body. Feathers are not evenly distributed over the surface of the body but arise in certain definite areas or feather tracts, the pterylae. Between the pterylae are the apteria or areas where the number of feathers are reduced or absent altogether. When feathers are present in an apterium, they consist mainly of a scanty distribution of downy and filoplumous feathers.

b. Development of the Avian Skin

1) Development of the Epidermis, Dermis, and Nestling Down Feather.

When the epidermal tube in the chick embryo begins to form, it consists of a single layer of cells of one cell in thickness. As development proceeds, this single-layered condition becomes transformed into a double layer, so that at 48 to 72 hours of incubation a two-layered epidermis is realized. This condition consists of an outer layer or periderm, considerably flattened, and an inner layer or stratum germinativum (fig. 269 A, B). At 96 hours of incubation in most parts of the developing integument, a primitive dermis is present as a loose aggregate of mesenchyme below the two-layered epidermis. The origin of a part of this mesenchyme from the dermatome is shown in figure 269C. At six days of incubation, mesenchyme is present as a definite dermal condensation (fig. 269D).

Between the sixth and eighth days of incubation, the epidermis and dermis increase in thickness, and small, mound-like protuberances begin to appear in certain areas (fig. 269E). Each elevation is produced by a mass of cells, known as the dermal papilla, which pushes the epidermal layer outward (fig. 269E). The initial dermal papillae represent the beginnings of the feather rudiments. At eleven days of incubation, many feather rudiments have made their appearance. Each rudiment consists of a central, mesenchymal (dermal) core or pulp, surrounded externally by epidermal cells. The dermal pulp is supplied copiously with small blood vessels (fig. 269F). The epidermal cells at this time are beginning to be arranged into longitudinal columns of cells. These longitudinal cellular columns represent the initial stages of barbrudiment development (fig. 270A). This condition of the developing feather marks the beginning of the first or the “nestling down” feathers.

At 12 to 14 days of incubation, the feather rudiment increases considerably in length and begins to invaginate into the dermal layer at its base (fig. 270B). This invagination of the base of the feather rudiment marks the beginning of definitive feather formation (Jones, ’07). In the developing feather from 14 to 17 days of incubation, two general regions are indicated. These regions of the developing feather are:

(a) a region from the surface of the skin to the distal end of the feather germ where the barbs and barbules of the nestling down are being formed (fig. 270B) and

(b) a proximal region below the surface of the skin where the barbs and barbules of the definitive feather begin to differentiate (fig. 27()B).

After the seventeenth day, the differentiation of the definitive feather proceeds rapidly (fig. 270C, D).

From the fourteenth to the seventeenth days, the barbs of the nestling down feathers elongate slightly by adding new ridge material at the basal end of each ridge (fig. 270B, C). The length of the barb rudiments of the down feather thus increases as the feather rudiment grows outward from the surface of the skin. As the barb rudiments elongate, they differentiate into the barbs and barbules (fig. 27 IB, C). (See Davies, 1889; Strong, ’02.) At about eighteen days of incubation, such a feather may be removed, and the distal portion of the horny sheath may be ruptured with a needle. Following the rupture of the horny sheath, the enclosed barbs will spread out as shown in the distal part of the developing feather in figure 270D.

At eighteen to twenty days of incubation, feather development in the chick may be represented as shown in figure 270C and D. A distal or nestlingdown-feather region and a proximal definitive-feather area are present. Barbs and barbules of the definitive feather differentiate in fhe-proximal area. A real quill is not established at the base of the nestling down feather, although a horny cylinder may intervene between the base of the down feather and the barbs of the definitive feather (fig. 270D). (See Jones, ’07.) Thus, in the chick and most birds, the first or nestling down feather and the succeeding definitive feather are developed as one continuous process, and cannot be regarded as two separate feather growths (Jones, ’07, p. 17). When me chick hatches, the outer horny sheath around the differentiated down feather dries and cracks open, and the barbs and barbules of the down feather spread out into fuzzy tufted structures (fig. 270D). Later, as the definitive feather emerges from the surface of the skin, the down-feather barbs appear as delicate tufts, attached to the distal ends of the barbs of the definitive feather (fig. 27 OE).

2) Development of the Contour Feather. The development of the contour feather is more complicated than that of the nestling down feather described above. Its development may be divided into early or primary and later or secondary phases (Lillie and Juhn, ’32). The formation of barbs during the early phase consists in the elaboration of barb and barbule rudiments without a shaft rudiment. This type of development resembles somewhat that of the down feather. The secondary phase of contour-feather development is concerned with the formation of a shaft, as well as the barb and barbule rudiments.

a) Formation of Barbs During the Primary or Early Phase of Contour-feather Formation. During the first phase of contour-feather formation, the barbs are formed in two different orders. The first order of barb rudiments arises more or less simultaneously (Lillie and Juhn, ’32); they are practically of the same size, about equal in number on either side, and dorsally placed. After this first set of barb rudiments is formed, a second order of barb rudiments arises in seriatim with the youngest barb rudiments, located more ventrally. (See first and second sets of barb rudiments in fig. 270D.) Both of these sets of barb rudiments eventually give origin to the barbs at the apical or distal end of the feather. As a shaft is not formed during the period when these two sets of barb rudiments are developing, i.e., during the first phase of definitive, contour-feather formation, these barbs later become associated with the forming shaft as the latter develops during the next or second phase of feather formation.

b) Secondary Phase of Contour-feather Formation. Following the formation of the barb rudiments mentioned above, the second phase of feather formation is initiated. It consists in the formation of the shaft and the further development of barb ridges and barbules. The development of the shaft is effected by the migration dorsalward of the collar cells (fig. 270E), which produces a continuous concrescence and fusion in the middorsal line of the two dorsal ends of the barb-bearing collar. This fusion of the collar cells forms the rudiment of the shaft as indicated in figure 270D. This concrescence of cells, however, establishes only the rudiment of the shaft, for it is apparent that the development of the shaft results from two sets of processes:

(1) the concrescence of a segment of the shaft rudiment at a particular point in the middorsal line of the feather rudiment and

(2) the elongation and growth of the rudiment material thus established.

As the shaft is laid down progressively from apex to base, the continuous concrescence of the collar cells and gradual formation of the shaft rudiment along the middorsal plane of the feather germ bring about the formation of the shaft (Lillie, ’40; Lillie and Juhn, ’32, ’38), beginning at its apex and progressing baseward.

As the collar material is fed into the developing shaft rudiment dorsally, the bases of the barbs, which are located in the collar or germinative ring, are carried continuously dorsalward and eventually become located along the sides of the shaft (fig. 270E). Also, the first set of barbs, which was formed in the first phase of contour-feather formation, becomes attached along either side of the developing shaft in the same way that the later barbs become attached.

In the formation of the barb, the apical or distal end of the barb is laid down by cellular contributions from the collar. Following this, more basal or proximal portions of the barb are elaborated by cellular deposition from the collar cells. The base of the barb thus remains attached to the collar as the barb rudiment elongates, while the apex maintains its position in the midventral line. As the base of the barb and the collar material to which it is attached move dorsalward toward the forming shaft, as observed in the previous paragraph, the base of the barb comes in contact with and fuses with the rachis or shaft, whereas the ventral extremity, i.e., the distal end of the barb, remains associated with the mesodermal pulp along the ventral aspect of the developing feather (fig. 271 A). The barb thus comes to form a half spiral around the developing feather within the external horny sheath (fig. 270E).|As successive barb rudiments are laid down, the previously formed barbs are moved progressively distad along with the mesodermal core.

c) Formation of the Barbules and the Feather Vane. During the period when the barbs are being formed, the side branches of the barbs or barbules are developed by the formation of groups of cells along either side of the barb (fig. 27 IB, C). Each of these groups of barbule cells differentiates into a barbule. A barbule thus represents a group of cells, specialized to form an elongated structure as shown in figure 27 ID. After the distal end of the feather extends markedly beyond the surface of the skin, the horny sheath breaks, and the barbs and barbules expand to form the vane of the feather. In doing so, the barbules interlock by means of barbicels which develop on the barbules, located on the side of the barbs facing toward the apex of the feather (fig. 271D).

d) Later Development of the Feather Shaft. During its development, the shaft gradually enlarges in the direction of the base of the feather. When the feather approaches its mature length, the shaft has enlarged to the extent that it comes to occupy the entire basal portion of the feather rudiment. As the last condition develops, barb formation becomes less exact until finally it is suppressed altogether. When this stage is reached, the contained dermal pulp within the base of the shaft begins to atrophy, starting at the end nearest the proximally placed barbs. As a result, a series of horny, hollow cells are formed within the base of the developing feather shaft. This hollow, basal end of the feather shaft forms the quill or calamus. The quill has a proximal umbilicus or opening through which the dermal pulp extends into the interior of the quill in the intact feather (fig. 27 lA). A distal umbilicus, from which the after feather emerges, may also be present in some feathers at the point where the ventral groove of the shaft meets the upper end of the quill.

Fig. 271. Diagrams of feather development. (A from F. R. Lillie: Physiol. Zool., 13; C and D redrawn from Strong: Bull. Mus. Comp. Zool. at Harvard, ’40.) (A)

Semidiagrammatic drawing of the pulp (papilla) of a regenerating feather. The axial artery of the feather is shown traversing the pulp to the distal end. The veins of the pulp (not shown) consist of a series of central and peripheral veins which connect with venous sinuses at the base of the pulp and, from thence, communicate with the cutaneous veins. (B) Part of transverse section of a feather follicle, showing the developing barbs and barbules. (C) Transverse section of a feather rudiment of the tern. Sterna hirundo. Pigment cells, within the barb substance, send out processes which distribute melanin to the cells of the developing barbule. (D) Middle portion of wing-feather barbule, showing pigment within individual barbule cells together with the distal barbicels with their booklets; comification is not complete.

3) Formation of the After Feather. The after feather emerges from the upper end of the quill of the contour feather. It is well developed in the unspecialized, contour feather but may be absent or represented merely by a few barbs in flight and tail feathers of the fowl (Lillie and Juhn, ’38). For a description of the after feather and its distribution in birds, reference may be made to Chandler (’16).

As observed above, when the rachis or shaft reaches a certain size, the development of barbs tends to be suppressed. A stage is reached ultimately when the barbs are irregular and not well formed. Consequently, the barbs near the quill lose all tendency to form a vane and are placed in an irregular fashion along the shaft. As this distortion of barb development occurs dorsally, some of the developing barbs on the ventral side of the enlarged shaft become physiologically and morphologically isolated from those which are moving dorsad in the normal fashion along the collar. As a result, they remain on the ventral surface and, in this position, they endeavor to form a twin feather. In doing so, they become attached in their isolated position to the ventral aspect of the forming quill. The superior umbilicus marks this point of attachment.

The degree of development of the after feather varies from the presence of a few barbs to a condition where a well-formed, miniature, secondary feather is developed. The secondary or after feather in this condition possesses a secondary rachis or aftershaft, known as the hyporachis, and is attached to the main rachis at the superior umbilicus.

4) Development of the Later Down and Filoplumous Feathers. The development of the later down or undercoat feather is similar to that of the nestling down feather, with the exception that a basal shaft or quill is formed to which the barbs become attached at the distal end of the quill. In the formation of the hair feather or filoplume, an elongated shaft of small diameter is formed to which a few small barbs may be attached at the distal end.

5. Mammals

a. Characteristics of the Mammalian Skin

The adult skin of manimals is characterized by a highly cornified, outer layer of the epidermis, together with the presence of numerous glands and hair. Hair, a distinguishing feature of the mammalian skin, is present in all species, with the exception of the Cetacea (whales) and the Sirenia (sea cows). Various types of horny structures are associated with the epidermis, while the dermis may develop plates of bone in certain instances. Both epidermis and dermis are of considerable thickness.

b. Development of the Skin

1) Development of the Skin in General. As in other vertebrates, the primitive mammalian integument is formed by the epidermal tube which, when first developed, consists of a single layer, one cell in thickness (fig. 272A). Later it becomes double layered, having an external flattened periderm and an inner stratum germinativum. As in other vertebrates, the germinative stratum is the reproductive layer. Mesenchyme condenses below the germinative stratum, and the rudiment of the future dermis is formed (fig. 272B).

In the further development of the epidermal layer, a third layer of cells, the stratum intermedium, appears between the periderm and the stratum germinativum (fig. 272C). The stratum germinativum or deep layer of Malpighi may appear to be several cells in thickness as development proceeds. The cells of the germinative stratum, in contact with the dermal surface, are cuboidal or cylindrical (fig. 272C, D). During later developrpent, the epidermis becomes highly stratified, and the outer or external layer is converted into a cornified layer, the stratum corneum (fig. 272D). Cornification occurs first on the future contact surfaces of the appendages, such as the volar surface of the hand, plantar surface of the foot, and foot pads of the cat, dog, etc. Pigment granules (melanin) appear in the deepest layers of the epidermis in the region of the basal, cylindrical cells of the stratum germinativum during later fetal development and after parturition (birth).

In the meantime, the dermal mesenchyme increases in thickness, and various types of connective-tissue fibers, white and elastic (see Chap. 15), appear in the intercellular substance between the mesenchymal cells. Pigment cells make their appearance in the dermis during later fetal development. These cells descend, probably, from cells of neural crest origin, although other mesenchymal cells possibly may contribute to the store of pigment-forming cells. Fat cells occur in the deeper layers of the dermis.

2) Development of Accessory Structures Associated with the Skin: a) Development of the Hair. The first indication of hair development is the formation of a localized thickening and invagination of the epidermal layer, particularly the germinative stratum (fig. 272E). This thickened mass of epidermal cells pushes inward, accompanied by an increase in the number of epidermal cells in the area of invagination (fig. 212V). Adjacent mesenchymal cells of the dermis respond to this epidermal activity by aggregating about the invaginating mass (fig. 272E, F). As the germinative stratum with its central core of cells continues to push downward in tangential fashion into the dermis, the surrounding mesenchyme forms a delicate, enveloping, connective-tissue sheath around the epidermal downgrowth (fig. 272G).

Fig. 272. Diagrams of developing hair. (A from Johnson: Carnegie Inst., Washington, Publ. No. 226, Contrib. to Embryol., 6; C and D from Pinkus, Chap. 10, The development of the integument, Keibel and Mall, 1910, Vol. 1, Lippincott, Phila.) (A) Section through epidermis of 24-somite human embryo. (B) Section through developing skin of 15-mm. cat embryo. (C) Section through 85-mm. human embryo, shov^ing threelayered epidermis. (D) Human skin, eight months, showing well-developed stratum corneum. (E) Early hair germ in human skin. (F) Later hair germ in human skin. (G) Still later hair germ, showing hair cone, sebaceous-gland rudiment, and epithelial bed. Observe that the hair cone arises as a result of the proliferative activity of the cells of the epithelial or hair matrix which overlies the mesenchymal papilla. Compare with fig. 273A.

As development continues, the distal portion of the germinative stratum forms a bulbous enlargement, the hair bulb. The mesenchymal rudiment of the papilla pushes into this bulb at its distal end to form the beginnings of the knob-like, definitive papilla of the future hair (fig. 272G). The hair rudiment then is formed by the proliferation of the epidermal cells, immediately overlying the knob-like papilla. The epithelial cells, overlying the papilla, form the epithelial matrix of the bulb (fig. 272G). The cells of the matrix soon produce a central core within the hair follicle, known as the hair cone (fig. 272G). The latter is a conical mass of cells which extends upward from the bulb into the center of the cellular material of the epidermal downgrowth. The hair cone thus gives origin to the beginnings of the hair shaft and the inner hair (epithelial) sheath (fig. 272G). The peripheral cells of the original epithelial downgrowth, which now surround the hair shaft and inner hair sheath, form the outer sheath (fig. 272G).

When the growing shaft of the hair reaches the level of the epidermal layer of the skin, it follows along a hair canal or opening in the epidermal layer and .finally erupts at the surface of the skin.

As the foregoing changes are effected, two epithelial growths appear along the lower surface of the obliquely placed, hair follicle (fig. 27 2G). The upper growth is the rudiment of the sebaceous gland which with certain exceptions generally is associated with hair development. The lower epithelial outgrowth forms the epithelial bed. This bed represents reserve epithelial material for future hair generations. The arrector pili muscle arises from adjacent mesenchymal cells and becomes attached to the side of the follicle (figs. 272G; 273). This muscle functions to make the hair “stand on end,” so noticeable in the neck-shoulder area of an angered dog.

The first hair to be developed is known as the down hair, fine hair or lanugo. In the human, the body is generally covered with lanugo by the seventh to eighth fetal month. It tends to be cast off immediately before birth or shortly thereafter. The lanugo corresponds somewhat to the nestling down of the chick, for the replacing hairs develop from the same follicles as the down hairs after the follicles have been reorganized from cells derived from the epithelial bed. However, some replacing hairs appear to arise from new hair follicles.

The hair on the face of the human female, exclusive of the eyebrows, nostrils, and eyelids, and also on the neck and trunk is of the fine-haired variety and resembles the lanugo of the fetus, whereas hair on the face of the human male is of the fine-haired type, exclusive of the eyebrows, eyelids, nostrils, and beard. Hair on various other regions of the male body may be of the fine-haired or lanugo variety.

b) Structure of the Mature Hair and the Hair Follicle. The general structure of the mature hair and its follicle is as follows: The hair itself consists of a shaft and a root (fig. 273A). The hair shaft is composed, when viewed in transverse section, of three regions of modified cells or products (fig. 273B). The innermost, central (axial) portion of the shaft is the medulla. It is composed of shrunken, cornified cells separated by air spaces. Surrounding the medulla, is the cortex, constructed of a dense horny substance interspersed with air vacuoles. External to the latter is the cuticle, made up of thin, cornified, epithelial cells with irregular outlines. The cuticle is transparent and glassy in texture. The pigment or coloring substance is contained within the cortical and medullary portions of the hair. Hair color is dependent upon two main factors:

( 1 ) the nature and quantity of pigment present and

(2) the amount of air within the cortex and medulla.

In some hairs, a distinct medullary portion may be absent.

Fig. 273. Diagrams of hair and follicle. (B redrawn from Maximow and Bloom, 1942, A Textbook of Histology. Saunders, Phila., slightly modified.) (A) Diagrammatic representation of the hair shaft and follicle in relation to skin. (B) Transverse section of hair shaft and follicle in skin of a pig embryo.

Fig. 274. Diagrams of nails, claws and hoofs. (A redrawn and modified from Pinkus, Chap. 10. The Development of the Integument, from Keibei and Mall, 1910, Vol. I, Lippincott, Phila.) (A) Longitudinal section of index finger of human fetus of 8.5 cm. (B) Longitudinal section of human finger, showing relationships of fully developed nail plate. (C) Claw of the cat, (D) Cloven hoof of the pig. (E) Developing hoof of pig. (F) Uncleft hoof of horse, lateral view. (G) Uncleft hoof of horse, ventral view.

While the shaft of the hair represents a cornified modification of epidermal cells, the root contains the cells in a viable condition before transformation into the cornified state. The root of the hair consists of the hair papilla, composed of dermal mesenchymal cells, blood vessels, nerve fibers, and a cupshaped epithelial matrix which overlies the papilla (fig. 273A). The hair shaft and the internal root sheath are derived from the modification of the cells of the hair matrix. The internal root sheath is composed of the inner sheath cuticle, together with Huxley’s and Henle’s layers (fig. 273B). The internal sheath disappears in the upper regions of the follicle near the entrance of the sebaceous gland. External to the internal root sheath is the external root sheath. The latter represents the wall of the epithelial follicle and is the downward continuation of the epidermal layer of the skin around the root of the hair. The external root sheath thus forms a pocket-like structure, extending from the distal margin of the hair matrix to the epidermis of the surface skin. A sheath of dermal cells and fibers lies around the external root sheath and acts as the skeletal support of the hair.

During development, hair first appears in the region of the eyebrows and around the mouth. Later it develops over the surface of the body in a regular pattern. This pattern tends to have a definite relationship to scales when present.

3) Development of Nails, Claws, and Hoofs. Resembling and closely linked to epidermal scales are the nails, claws, and hoofs of mammals. The claws of reptiles and birds belong to the same category of terminal protective devices for the digits. Nails are flattened discs of horny material, placed on the dorsal surfaces of the terminal phalanges (fig. 274A, B). Claws are similar and represent thickened, laterally compressed, and pointed nails (fig. 274C). Hoofs are composite structures on the terminal phalanges of the digits, but, unlike nails and claws, they are composed of two much-thickened nails, one dorsal and one ventral.

The distal protective device of the human digit is composed of a dorsal structure, the nail plate or unguis. A formidable, horny subunguis or ventral nail plate is absent, although a subungual region, consisting of an area of extreme cornification of the stratum corneum of the skin, is present (fig. 274B), The claw of the cat or dog is similar, with the nail plate compressed laterally, and the subungual cornification is greater. On the other hand, hoofs possess a dorsal nail plate (unguis) and a well-developed ventral nail plate (subunguis). Hoofs may be further divided into two general groups. In one group are the hoofs of cows, sheep, deer, etc., which form two, nail-forming mechanisms at the terminus of the digit, one dorsal and one ventral, from which the dorsal and ventral nail plates arise. In the other group are the hoofs of horses, donkeys, zebras, etc., which develop a dorsal, nail-developing mechanism, forming the dorsal nail plate, and two ventral, nail-producing structures. One of the latter generative devices gives origin to the frog and the other to the ventral nail plate. Thus, embryologically, nails and claws belong to one group, whereas hoofs form another.

A better appreciation of the above-mentioned facts relative to claws, nails, and hoofs can be gained by considering the development of a relatively simple, terminal structure of the digit, the human finger nail.

The nails on the terminal digits of the developing human finger begin to form when the embryo (fetus) is about three months old. In doing so, a thickened epidermal area arises on the dorsal aspect of the terminal end of the digit. This general, thickened, epidermal area constitutes the nail field. The proximal portion of the nail field then invaginates in a horizontal direction, passing inward into the underlying mesenchyme toward the base of the distal phalanx. This invaginated epidermal material forms the nail fold or groove, and it lies within the mesenchyme, paralleling the overlying epidermis (fig. 274A). The nail fold, when viewed from above, is a crescent-shaped affair with the outer aspect of the crescent facing distally; it may be divided into a deeper layer, the nail matrix, and a more superficial layer. The nail matrix is confined almost entirely within the nail fold or groove. The distal edge of the lunula marks its greatest extension distally along the nail field.

At about the fifth month, the upper cells of the nail matrix begin to keratinize, and the keratinized cells gradually fuse into the compact nail plate, ^as new material is added to the nail plate from the cells of the matrix, the distal portion of the plate is pushed progressively toward the end of the digit (fig. 274A). Although that portion of the nail field between the terminal end of the digit and the lunula takes no part in the formation of the cornified material of the nail plate, the underlying dermis below the nail field does form elongated ridges which push upward into the epidermis of the nail field. These ridges secondarily modify the already-formed nail plate by producing fine, longitudinal lines or ridges.

The claw or nail plate of the cat is compressed laterally to form a narrow, sickle-shaped structure. Three main factors are responsible for this peculiar form of the nail plate in the cat. One factor is the laterally compressed form of the distal phalanx. This condition results in a nail-fold invagination which is laterally compressed. The nail matrix thus is elliptical in shape, dorsoventrally, instead of flattened as in the human finger. A second factor responsible for the extreme, claw-shaped form of the nail plate in the cat is the more rapid growth in the middorsal portion than in the lateral areas of the nail plate. This discrepancy in growth results in the highly pointed midregion at the distal end of the nail plate. Ventrally, the two lateral sides of the nail plate tend to approach each other. The area between these two sides is filled with a cornified mass of subungual material. A final factor governing the extreme pointedness of the cat’s claw is the fact that the claw-distalphalanx arrangement, relative to the middle phalanx and tendons, makes the claw retractile when not in use, thus preserving its pointed distal end (fig. 274C).

The dog’s claw or nail on the ordinary digits is compressed laterally less than that of the cat, with the result that the subungual cornification is broader and more pronounced and the distal end of the claw not as pointed. However, the claws upon the vestigial first digit, the so-called dewclaws, are pointed and cat-like. The fact that the claw of the dog is non-retractile is a factor in reducing its pointedness, for it, unlike the cat’s retractile claw, is worn down continually.

The cloven hoof of the pig or cow is produced by the formation of two nail plates, one dorsal and one ventral, around each of the distal phalanges of the third and fourth digits (fig. 27 4E). The dorsal nail plate is rounded from side to side and meets the lower nail plate ventrally, with which it fuses along the lateral and distal portions of the lower plate. The unsplit hoof of the horse is produced by a somewhat similar arrangement of dorsal and ventral nail plates around the hoof-shaped phalanx of the third digit (fig. 274F, G). A third nail plate or growth center produces the frog or cuneus.

4) Development of Horns. The horns of cattle arise as two bony outgrowths, one on either side of the head, from the area of the parietofrontal bones of the skull. In most instances the frontal bone alone is involved. Each bony outgrowth pushes the epidermis before it. The epidermis then responds by producing a highly keratinized, horny substance around the outgrowing bone. The result is the formation around the bony outgrowth of an unbranched cone (or horn) of cornified epidermal material (fig. 275 A). This type of horn grows continuously until the mature size is reached. If removed, this type of horn will not regenerate. Horns of this structure are found in sheep, goats, cattle, and antelopes.

The horns of the pronghorn, Antilocapra americana, are somewhat similar to those of cattle, with the exception that the external, keratinized, slightly branched, horny covering, overlying the bony core, is shed yearly, to be replaced by a new horny covering (fig. 275B).

On the other hand, the antlers of the deer offer a different developmental procedure. A new bony core is formed each spring which grows and forms the mature antler. As this hard, bony antler matures during late summer and early autumn, the outside covering of epidermis (i.e., the velvet) eventually atrophies and drops off, leaving the very hard, branched, bony core or antler as a formidable fighting weapon for use during the breeding season (fig. 275C). When the latter period is past, the level of the male sex hormone falls in the blood stream, which brings about a deterioration of the bony tissue of the antler near the skull. This area of deterioration continues until the connection to the frontal bone becomes most tenuous, and the antlers fall off, i.e., are shed. (See Chap. 1, p. 27.)

The horns of the giraffe are simple, unbranched affairs which retain the velvet or epidermal covering around a bony core. The horns of the rhinoceros are formidable, cone-shaped, median structures (one or two), composed of a keratinized, hair-like substance. These horns are located on the nasal and frontal bones. (For a discussion of horns in the Mammalia, see Anthony, ’28, ’29.)

Fig. 275. Horns of mammals. (A) Cow. (B) Prong-horn antelope. (C) White-tailed deer.

5) Development of the Skin Glands. Three types of glands develop in relation to the skin in mammals:

( 1 ) sebaceous or oil glands,

(2) sudoriferous or sweat glands, and

( 3 ) mammary or milk glands.

a) Sebaceous Glands. Sebaceous glands generally are associated with the hair follicles (figs. 272G; 273 A), but in some areas of the body this association may not occur. For example, in the human, sebaceous glands arise independently as invaginations of the epidermis in the region of the upper eyelids, around the nostrils, on the external genitals, and around the anus. When the sebaceous gland arises with the hair follicle, it generally takes its origin from the lower side of the invaginated hair follicle, although this condition may vary (fig. 272G). The sebaceous-gland rudiment originates as an outpushing of the germinative stratum and differentiates into a simple or compound alveolar type of gland. The secretion originates as fatty material within the more centrally located cells of the gland, with subsequent degeneration of these cells and release of the oily substance. Since the secretion forms as a result of alteration of the gland cells themselves, this type of gland is classified as an holocrine gland. New cells are formed continuously from that portion of the gland connected with the germinative stratum. The oil produced is discharged to the surface of the skin through the opening of the hair follicle when a relationship with the hair is present. If not connected with a hair follicle, the gland has a separate opening through the epidermal layer.

b) Sudoriferous Glands. Sweat or sudoriferous glands most often develop independently of hair follicles, but in certain areas they form on the sides of these follicles. Whenever formed, they represent solid, elongated ingrowths of the epidermis into the dermis. Later these cellular cords coil at their distal ends to form simple, coiled, tubular glands (fig. 276).

The outer wall of the forming sweat gland develops so-called myoepithelial cells; the latter presumably have the ability to contract. The cells lining the lumen of the gland secrete (excrete) the sweat, the distal ends of the cells being discharged with the exudate. Hence, this type of gland is called an apocrine gland. The secretion is watery and contains salts, wastes, including urea, and occasionally some pigment granules and fat droplets. In the cat, dog, and other carnivores, sweat glands are reduced in number.

c) Mammary Glands. Mammary glands are characteristic of the mammals. The first indication of mammary-gland development is the formation of the milk or mammary ridges (fig. 24 ID, E). These ridges represent elevations of the epidermis, extending along the ventro-lateral aspect of the embryo from the pectoral area posteriad into the inguinal region. The ridges are developed in both sexes and represent a generalized condition of development. In the human embryo, the mammary ridge is well developed only in the pectoral region, but it is extensive in the pig, dog, and cat. In the cow, horse, deer, etc., its greatest development is in the inguinal area.

Fig. 276. Diagram of sudoriferous (sweat) gland.

Only very restricted areas of each mammary ridge on either side are utilized in mammary-gland development. In the pig or dog embryo, a series of localized thickenings begin to appear along the ridge. In the sheep, cow, and horse, these thickenings are confined to the inguinal region, whereas in the primates and the elephant, they are found in the pectoral area. In the human, one thickening in each ridge generally appears, although occasionally several may arise. These thickenings represent the beginnings of the nipples and result from increased proliferations of cells (fig. 277B). Eventually, each thickened portion of the ridge becomes bulbous and sinks inward into the dermis (fig. 277C). Gradually, solid cords of cells push out from the lower rim of the solid epidermal mass into the surrounding dermal tissue (fig. 277D). These cords of cells represent the rudiments of the mammary-gland ducts. Secondary outpushings appear at the distal ends of the primary ducts. Later, lumina appear in the primary ducts. Further development of these ducts, with the formation of the terminal rudimentary acini, occurs during late fetal stages, resulting in the formation of an infantile state. This condition is found at birth in the human, dog, cat, etc. Under the influence of hormones present in the blood stream of the mother (see Chap. 2, p. 103), these acini may secrete the so-called “witch’s” milk in the newborn human male and female. While the occurrence of this type of milk secretion is not uncommon, the gland as a whole is in a rudimentary, undeveloped state. It remains in this infantile condition until the period of sexual development when, in the female, the mammary-gland ducts and attendant structures begin to grow and develop under the influence of estrogen, the female sex hormone. (See Chap. 2.) It should be observed that the rounded condition of the developing breast in the human female at the time of puberty (fig. 277F) is due largely to the accumulation of fat and connective tissue and not to a great extension of the duct system of the glands, although some duct extension does occur at this time.

As the original epithelial thickening of the nipple rudiment sinks inward, the center of the thickened area moves downward to a greater extent than the margins. Some disintegration of the central cells also occurs. As a result, a slight cavity or crater-like depression is formed in the middle of the epithelial mass of the rudiment (fig. 277C). In the cow and rat, this depressed area continues in this state, while the edges of the cavity and adjacent integument grow outward to form the nipple (fig. 277E). This type of nipple is called an inversion nipple. The ducts of the gland thus open into the bottom of the nipple (teat or mammilla). In the human, the original depression and the openings of the primary ducts of the gland gradually are elevated outward to form the type of nipple or mammilla indicated in figure 277 A. This type of nipple is called an eversion nipple.

Fig. 277. Diagrams showing mammary-gland development. (A) Human nipple showing mammary duct openings. (Modified from Maximow and Bloom, A Textbook of Histology, after Schaffer, 1942, Saunders, Phila.) (B) Transverse section of early nipple rudiment of 20-mm. pig embryo. (C) Transverse section through developing nipple of pig embryo of 70 mm., showing epidermal invagination into the dermal area of the skin. (D) Section through nipple of mammary gland of human male fetus, eight months old. (After Pinkus, Keibel and Mall: Manual of Human Embryology, Vol. I, 1910, Lippincott, Phila.) (E) Section through developing nipple of newborn rat. (Redrawn and modified from Myers, ’16, Am. J. Anat., 19.) (F) Development of human mammary gland from birth to maturity.

As indicated above, the distribution of nipples and mammary glands along the ventral abdominal wall varies greatly in different mammalian species. In lemurs and fruit bats, the mammary glands are developed in the axillary region; in the human and in primates, they are pectoral; in the cat, they are best developed in the pecto-abdominal area; in the dog and pig, they are mainly well developed in the abdominal and inguinal areas; in the cow and horse, inguinal nipples only appear; and in whales, the mammary glands are located near the external genitals.

The development of supernumerary mammary glands, i.e., hypermastia, is rare, but the formation of extra nipples, i.e., hyperthelia, is common in both male and female. In female mammals, such as the bitch, it is not uncommon for the breasts to remain in an undeveloped condition in the pectoral area, whereas those in the inguinal and abdominal areas are normal. When the mammary glands continue in an undeveloped or regressed state as, for example, in the anterior pectoral region of the bitch, the condition is known as micromastia. On the other hand, the abnormal development of the mammary glands to an abnormal size is known as macromastia. The latter condition often is found in cattle and occasionally in the bitch and human.

C. Coloration and Pigmentation of the Vertebrate Skin and Accessory Structures

1. Factors Concerned with Skin Color

The color of the skin and its accessory structures is dependent upon five main factors:

( 1 ) the color of the skin itself,

(2) its opacity or translucency,

(3) the presence of pigment granules and special, pigment-bearing cells,

(4) the capillary bed of blood vessels which lies within the dermal portion of the skin, and

(5) the color of the accessory structures.

The color of the skin itself varies considerably in different species, but it tends to be slightly yellow, resulting from the presence of fatty tissue, fat droplets, and constitutent, connective-tissue fibers in the dermis. The property of opacity or translucency is an important factor for upon it depends transmission of light waves through the skin from deeper lying structures, such as blood vessels, pigment droplets, pigment-bearing cells, etc. The presence of definite types of pigment granules within or between the cells of the epidermis and dermis determines the course and kind of light waves which are reflected. The richness or paucity of blood vessels, ramifying through the dermal area, also affects the skin’s color in many instances.

The color of the accessory structures, particularly the structures derived from the epidermis, greatly conditions the color pattern of the species. The color of these accessory structures is dependent upon three main factors:

( 1 ) presence or absence of pigment,

(2) presence of air, and

(3) iridescence.

Pigment and air are dominant factors, for example, in the color exhibited by hair and feathers. The presence of air diminishes and distorts the effects of the pigment which may be present. The property of iridescence is to be distinguished from the color effects due to the presence of certain pigments; the latter absorb light rays and reflect them, whereas iridescence is dependent upon the diffraction of light waves from irregular surfaces. Iridescence is important in the color effects produced by the plumage of a bird or the skin surface of many fish, reptiles, and amphibia.

2. Color Patterns

In the vertebrates whose manner of life dictates a close association of the body with the environmental substrate, the underparts have less color than the parts exposed to the light rays coming from above. Also, within the general, colored areas, there are certain spots, lines, bars, and dark and light regions which follow a definite pattern more or less peculiar to the variety, subspecies, or species. These color patterns tend to be fixed and are determined by the heredity of the animal. Consequently, they are related to the genic complex in some way. However, in many species the tone of the color patterns may be changed from time to time by changing environmental conditions as mentioned on page 594.

3. Manner of Color-pattern Production a. Role of Chromatophores in Producing Skin-color Effects

Work in experimental embryology has demonstrated fairly conclusively that the pigments necessary for color formation are elaborated principally by certain cells known as chromatophores. Chromatophores are pigment-bearing and pigment-elaborating cells. Various cells may produce pigment, but chromatophores are cells specialized in the function of pigment elaboration.

The distribution and activities of chromatophores vary in the different vertebrate groups. For example, in fishes, amphibia, and many reptiles, three or probably four kinds of chromatophores are present in the dermis, namely, melanophores, lipophores, guanophores, and (possibly) allophores (Nobel, ’31, p. 141). By their presence and arrangement, the chromatophores produce specific color patterns. Moreover, the expansion and contraction of the pigmented cytoplasm of some or all the chromatophores effects changes in color, for the contracted or expanded state determines the types of light rays which will be absorbed or reflected. The rapid color changes in certain tree frogs and lizards are due to this type of chromatophoric behavior. The slower changes of color in other amphibia and fishes also are due to this type of chromatophoric activity. It thus appears that dermal chromatophores are responsible largely for the color effects found in the lower vertebrates. On the other hand, in the bird group and in mammals, the chromatophores present are mainly of one type, known as a melanophore. Melanophores produce pigments, known as melanins (Dushane, ’44, p. 102). The melanin granules, elaborated by the bird melanophore, have a wide range of color from yellow through orange to reddish-brown to dark brown. The melanophores in the bird deposit the melanin-pigment granules within the feather as it develops (fig. 271C) . Melanophores also deposit melanins in the bill of the male sparrow at breeding time under the influence of the male sex hormone (Witschi and Woods, ’36). Hair color in mammals is due, mainly, to pigmented granules deposited in the hair by melanophores. The skin color of various races of the human species is determined largely by the amount of melanin deposited within the lower epidermal layers by melanophores resident in the upper dermal area. In other words, the color of the skin and its appendages in the higher vertebrate groups is due, to a considerable extent, to diffuse granules deposited in the epidermis and epidermal structures by melanophores, whereas, in lower vertebrates, dermal chromatophores are responsible for color pattern and color change.

b. Activities of Other Substances and Structures in Producing Color Effects of the Skin

In the common fowl, the presence of carotenoids (lipochromes) in the Malpighian layer (stratum germinativum) mainly is responsible for the color of the face, legs, and feet. Orange-red, lipochromic droplets have been found in the germinative stratum of the head of the pheasant, and these droplets plus the capillaries in the dermis produce a brilliant red coloration (Dushane, ’44, p. 102). The color of the combs and wattles of the common fowl is conceded generally to be due to the presence of a rich capillary plexus in the dermis alone. In the ear regions of the fowl, the blood capillaries are reduced in the dermis, and the presence of certain crystals of unknown chemical composition produces a double refraction of the light waves. Hence, the ear region appears white in reflected light.

c. Genic Control of Chromatophoric Activity

The transplantation of small pieces of epidermis and its adhering mesoderm from one early chick embryo to another is possible. Under these conditions, the donor tissue with its donor melanophores governs the color pattern of the feathers developed in the are^ of the transplant (Willier and Rawles, ’40). That is, melanophores from a Black Minorca embryo, transplanted to a White Leghorn embryo, will produce a Black Minorca color pattern, in the White Leghorn in the area of transplant, at least during the development of nestling down and juvenile feathers. Barred Rock melanophores produce barreo feather patterns in White Leghorn, New Hampshire Red, Black Minorca, etc. These results demonstrate that the introduced melanophore produces the color pattern in the feather in the immediate area of the implant.

Various genetic studies (see Dushane, ’44, for references) have demonstrated that the Barred Rock factor is dominant, and that it is sex-linked. For example, if a Barred Rock hen is crossed with a Rhode Island Red cock, the Fi male will contain two sex chromosomes, one from each parent. That chromosome from the female parent will have a Barred Rock factor, whereas that from the male parent will not. The Fj cock, therefore, is heterozygous for barring, and, as the barring factor is dominant, the Fi cock will show barred feathers. The Fi female, however, derives its single sex chromosome from the male parent; as this chromosome does not contain the barring factor, the Fi female is black.

Willier (’41) presents evidence concerning the transplantation of melanophores from Fi heterozygous males and Fi heterozygous females of this Barred Rock cross. Transplanted melanophores from an Fi male into White Leghorn hosts always produce barred contour feathers in either sex, whereas Fi female melanophores transplanted to White Leghorn hosts always produce non-barred or black regions. Danforth (’29) demonstrated that the barring factor in the skin of the male donor at hatching, when transplanted to a female host at hatching which lacked the barring factor, produces barred feathers in the female host in the area of the transplant. The results obtained by Danforth suggest that the barring gene acts independently of the sex hormone, although the feather type present in the graft assumes the female characters of the host and, hence, is affected by the female sex hormone. The results of these experiments by Willier and Danforth suggest that the barring gene in poultry acts directly upon the melanophore and not upon the environment in which the melanophore functions. (For extensive description, references, and discussion of these phenomena, consult Danforth, ’29; Willier, ’41; and Dushane, ’44.)

d. Examples of Hormonal Control of Chromatophoric Activity

In the indigo bunting, the male resembles the female during the non-breeding season. During the breeding season, however, the male develops a brilliant, purple-colored, highly iridescent plumage. Castration experiments and gonadotrophic hormone administration suggest that this nuptial plumage is dependent, not upon the male sex hormone, but upon gonadotrophic hormones elaborated by the pituitary gland in the male. In the female, however, the presence of the female sex hormone inhibits the effects of the pituitary gonadotrophins; hence, she retains the sexually quiescent type of plumage (Domm, ’39, p. 285). Also, in certain cases where the color of the bird’s bill is a sex-dimorphic character appearing during the breeding season only, it has been shown that the pigmentation of the bill is dependent upon the presence of the male sex hormone (Domm, ’39).

e. Environmental Control of Chromatophoric Activity

The above-mentioned instances of color-pattern development are concerned with the elaboration and deposition of pigment within the epidermis and epidermal structures. On the other hand, other observations demonstrate that the contraction and expansion of chromatophores and, hence, the production of different tones of color patterns, may be effected by a variety of environmental stimuli in lower vertebrates. In some cases this may be due to direct stimulation of the chromatophores by light or darkness or by changes in temperature; in other instances the causative factor is a secretion from certain glands, such as the pituitary or adrenal glands. The latter secretions in some forms appear to be aroused by light waves to the eye, from whence the stimulation is relayed through the nervous system to the respective gland or glands. In still other instances the light waves to the eye may cause a direct stimulation of the chromatophores by means of nerve fibers which reach the chromatophores. Other examples suggest that certain neurohumoral substances, elaborated by the terminal fibers of the nerves some distance away from the chromatophore, slowly diffuse to the chromatophore, causing its expansion or contraction (Noble, ’32, pp. 141-147; Parker, ’40).


Anthony, H. C. 1928; 1929. Horns and antlers, their evolution, occurrence, and function in the Mammalia. Bull. New York Zool. Soc. 31; 32.

Bardeen, C. R, 1900. The development of the musculature of the body wall in the pig. Johns Hopkins Hosp. Rep. 9:367.

Chandler. A. C. 1916. A study of the structure of feathers with reference to their taxonomic significance. University of California Publ., Zool. 13:243.

Danforth, C. H. 1929. Genetic and metabolic sex differences, J. Hered- 20:319.

Davies, H. R. 1889, Die Entwicklung der Feder und ihre Beziehungen zu anderen Integumentgebilden. Morph. Jahrb. 15:560.

Dawson, A. B. 1920. The integument of Necturus maculosus. J. Morphol. 34:487.

Domm, L. V. 1939. Chap. V. Modifications in sex and secondary sexual characters in birds in Sex and Internal Secretions by Allen, Danforth, and Doisy. 2d ed. The Williams & Wilkins Co., Baltimore.

Dushane, G. P. 1943. The embryology of vertebrate pigment cells. Part I. Amphibia. Quart. Rev. Biol, 18:109.

. 1944. The embryology of vertebrate pigment cells. Part II. Birds. Quart. Rev. Biol. 19:98.

Eastlick, H. L. and Wortham, R. A. 1946. An experimental study on the featherpigmenting and subcutaneous melanophores in the silkie fowl. J. Exper. Zool. 103:233.

Engert, H. 1900. Die Entwicklung der ventralen Rumpfmuskulatur bei Vbgeln, Morph. Jahrb. 29:169.

Eycleshymer, A. C. 1906. The development of chromatophores in Necturus, Am. J. Anat. 5:309.

Greene, C. W. 1899. The phosphorescent organs in the toad-fish, Porichthys notatus Girard. J. Morphol. 15:667.

Harms, J. W. 1929. Die Realisation von Genen und die consecutive Adaption. I. Phasen in der Differenzierung der Anlagenkomplexe und die Frage der Landtier-werdung. Zeit. Wiss. Zool. 133:211.

Jones, L. 1907. The development of nestling feathers. Oberlin College Lab. Bull. No. 13.

Lillie, F. R. 1940. Physiology of development of the feather. III. Growth of the mesodermal constituents and blood circulation in the pulp. Physiol. Zool. 13:143.

and Juhn, M. 1932. The physiology of development of feathers. 1. Growth rate and pattern in the individual feather. Physiol. Zool. 5:124.

and . 1938. Physiology of

development of the feather. II. General principles of development with special reference to the after-feather. Physiol. Zool. 11:434.

Neave, F. 1936. The development of the scales of Salmo. Tr. Roy. Soc. Canada. 30:550.

. 1940. On the histology and regeneration of the teleost scale. Quart. J. Micr. Sc. 81:541.

Nickerson, W. S. 1893. The development of the scales of Lepidosteus. Bull. Mus. Comp. Zool. at Harvard College. 24:115.

Noble, G. K. 1931. The Biologv of the Amphibia. McGraw-Hill Book Co., Inc., New York.

Parker, G. H. 1940. Neurohumors as chromatophore activators. Proc. Am. Acad. Arts & Sc. 73:165.

Sayles, L. P. and Hershkowitz, S. G. 1937. Placoid scale types and their distribution in Squalus acanthias. Biol. Bull. 73:51.

Strong, R. M. 1902. The development of color in the definitive feather. Bull. Mus. Comp. Zool. at Harvard College. 40: 146.

Williams, L. W. 1910. The somites of the chick. Am. J. Anat. 11:55.

Willier, B. H. 1941. An analysis of feather color pattern produced by grafting melanophores during embryonic development. Am. Nat. 75:136.

and Rawles, M. E. 1940. The control of feather color pattern by melanophores grafted from one embryo to another of a different breed of fowl. Physiol. Zool. 13:177.

Witschi, E. and Woods, R. P. 1936. The bill of the sparrow as an indicator for the male sex hormone. 11. Structural basis. J. Exper. Zool. 73:445.

Tke Digestive System

A. Introduction

1. General structure and regions of the early digestive tube or primitive metenteron

a. Definition

b. Two main types of the early metenteron

2. Basic structure of the early metenteron (gut tube)

a. Basic regions of the primitive metenteron

1 ) Stomodaeum

2) Head gut or Seessel’s pocket

3) Foregut

4) Midgut

5) Hindgut

6) Tail gut (post-anal gut)

7) Proctodaeum

b. Basic cellular units of the primitive metenteron

3. Areas of the primitive metenteron from which cvaginations (diverticula) normally arise

a. Stomodaeum

b. Pharynx

c. Anterior intestinal or pyloric area

d. Junction of midgut and hindgut

e. Cloacal and proctodaeal area

B. Development of the digestive tube 6r metenteron

1. General morphogenesis of the digestive tube

2. Histogenesis and morphogenesis of special areas a. Oral cavity

1 ) General characteristics of the stomodaeal invagination

2) Rudiments of the jaws

3) Development of the tongue

4) Teeth

a) General characteristics

b) Development of teeth in the shark embryo

c) Development of teeth in the frog tadpole

d) Development of the egg tooth in the chick

e) Development of teeth in mammals

5) Formation of the secondary palate

6) Formation of the lips

7) Oral glands




b. Development of the pharyngeal area

1 ) Pharyngeal pouches and grooves

2) Pharyngeal glands of internal secretion

3) Other respiratory diverticula

c. Morphogenesis and histogenesis of the esophagus and the stomach region of the metenteron

d. Morphogenesis and histogenesis of the hepato-pancreatic area

1 ) Development of the liver rudiment

a) Shark embryo

b) Frog embryo

c) Chick embryo

d) Pig embryo

e) Human embryo

2) Histogenesis of the liver

3) Development of the rudiments of the pancreas

a) Shark embryo

b) Frog embryo

c) Chick embryo

d) Pig embryo

e) Human embryo

4) Histogenesis of the pancreas

e. Morphogenesis and histogenesis of the intestine

1) Morphogenesis of the intestine in the fish group

2) Morphogenesis of the intestine in amphibia, reptiles, birds, and mammals

3) Torsion and rotation of the intestine during development

4) Histogenesis of the intestine

f. Differentiation of the cloaca

C. Physiological aspects of the developing gut tube

A. Introduction

1. General Structure and Regions of the Early Digestive Tube or Primitive Metenteron

a. Definition

The word metenteron is applied to the gut tube which is developed from the archentcric conditions of the gastrula. The term primitive metenteron may be applied to the gut tube shortly after it is formed, that is, shortly after tabulation of the entoderm to form the primitive gut tube has occurred, while the word metenteron, unqualified, is applicable to the tubular gut, generally, throughout all stages of its development following the gastrular state.

b. Two Main Types of the Early Metenteron

Two types or morphological forms of early vertebrate metenterons are developed immediately after the gastrular stage. In one type, such as is found in the frog and other amphibia, ganoids, cyclostomes, and lungfishes, the walls of the gut tube are complete^ and the yolk material is enclosed principally within the substance of the midgut area of the tube (fig. 217). In the second









VENTRAL pancreas

small intestine











Fig. 278. Diagrams showing basic features of digestive-tube development in the vertebrates. (A) The regions of the primitive gut where outgrowths (diverticula) normally occur. (B) Basic cellular features of the gut tube. (C) Contributions of the basic cellular composition to the adult structure of the digestive tract. Consult Fig. 293 for actual structure of mucous layer in esophagus, stomach, and intestines.

type, on the other hand, most of the yolk material lies outside the confines of the primitive gut tube (fig. 217), and the midgut region of the primitive tube is open ventrally, the ventro-lateral walls of the tube being incomplete. The latter condition is found in elasmobranch fishes, reptiles, birds, and primitive mammals. In higher mammals, although yolk substance is greatly reduced, the arrangement is similar to that of the latter group. The teleost fishes represent a condition somewhat intermediate between these two major groups.

2. Basic Structure of the Early Metenteron (Gut Tube)

(Consult figs. 278A; 279A; 280A; 281 A; and 282B.)

a. Basic Regions of the Primitive Metenteron

The primitive vertebrate metenteron possesses the following regions.

1) Stomodaeum. The stomodaeum lies at the anterior extremity of the gut tube, and represents an ectodermal contribution to the entodermal portion of the primitive gut. It results from an invagination of the epidermal tube directed toward the oral evagination of the foregut. The membrane, formed by the



apposition of the oral evagination of the foregut and the stomodaeal invagination of the epidermal tube, constitutes the oral or pharyngeal membrane. Ectoderm and entoderm thus enter into the composition of the pharyngeal membrane. This membrane normally atrophies.

2) Head Gut or Seessel’s Pocket. This structure represents the extreme anterior end of the foregut which projects forward toward the anterior end of the notochord and brain. It extends cephalad beyond the region of contact of the stomodaeum with the oral evagination of the foregut. During its earlier period, the head gut is intimately associated with the anterior end of the


Fig. 279. Morphogenesis of the digestive structures in the dog fish, Sqiuilus acanthias. See also Figs. 29 1C and 296 A.



notochord and the pre -chordal plate mesoderm. The head gut ultimately degenerates. Its significance probably lies in its function as a part of the head organizer.

3) Foregut. The foregut comprises the anterior portion of the primitive metenteron from the region of the stomodaeum and Seessel’s pocket, posteriorly to the intestinal area where arise the liver and pancreatic diverticula. It is divisible into four general regions:

(1) pharyngeal area,

(2) esophagus,

(3) stomach, and

(4) hepatopyloric segment.

4) Midgut. The midgut area of the gut tube is the general region lying between the foregut and hindgut regions. This segment of the primitive gut eventually differentiates into the greater part of the small intestine. In the early metenteron, the midgut area is concerned with the digestion of yolk material in such forms as the frog or with the elaboration of the yolk sac in the shark, chick, reptile, and mammalian embryos. In addition, it appears that the primitive blood cells also are elaborated in this area. (Sec Chap. 17.)

5) Hindgut. This portion of the early gut tube is located posteriorly, immediately anterior to the proctodacum.

6) Tail Gut (Post-anal Gut). The tail gut represents a dorsal, posterior continuation of the hindgut into the developing tail. As indicated in Chapter 10, it is extremely variable in the extent of its development. (Consult also fig. 217.)

7) Proctodaeum. The epidermal invagination, which meets the proctodaeal or ventral evagination of the hindgut, forms the proctodaeum. The anal membrane results when the proctodaeal inpushing meets the entodermal outpushing of the hindgut. The anal membrane is double, composed of entoderm and ectoderm. It is destined to disappear.

b. Basic Cellular Units of the Primitive Metenteron

Most of the lining tissue of the primitive metenteron is derived from the entoderm of the archenteric conditions of the late gastrula. Associated with the strictly entodermal portion of the primitive metenteron are two contributions of the epidermal tube as observed on pages 598 and 600, namely, the stomodaeum and the proctodaeum. Added to this lining tissue are mesenchymal contributions, derived from the medial or splanchnic layers of the hypomeric mesoderm (fig. 278B).

The glandular structures of the digestive tube are derived as modifications of the lining tissue of the stomodaeal, entodermal, and proctodaeal portions of the primitive gut tube, whereas muscular and connective tissues differentiate from mesenchyme (fig. 278C).



3. Areas of the Primitive Metenteron from which Evaginations (Diverticula) Normally Arise

Certain areas of the primitive metenteron tend to produce outgrowths (evaginations; diverticula). The following comprise these areas (fig. 278A).

a. Stomodaeum

In the middorsal area of the stomodaeum, a sac-like diverticulum or Rathke’s pouch, invaginates dorsally toward the infundibulum of the diencephalic portion of the brain. It remains open for a time and thus retains its connection with the oral epithelium. Later, however, it loses its connection with the oral cavity and becomes firmly attached to the infundibulum of the brain. It eventually forms the anterior lobe of the hypophysis or pituitary gland. (See chapters 1, 2, and 21.) Other diverticula of the oral (stomodaeal) cavity occur. These evaginations form the rudiment of the oral glands and will be discussed on page 617.

b. Pharynx

The pharyngeal area or pharynx represents the anterior portion of the foregut, interposed between the stomodaeum or oral cavity and the esophagus. This general region has four main functions:

( 1 ) external respiration,

(2) food passage (alimentation),

(3) endocrine-gland formation, and

(4) development of buoyancy structures.

In most vertebrates, five or six pairs of lateral outgrowths, known as the visceral or branchial pouches are formed. A ventral outpocketing or outpocketings also occur in all vertebrates. The thyroid-gland diverticulum is the most constantly formed ventral outgrowth, but lung and air-bladder evaginations are conspicuous in most vertebrate species. Dorsal and dorso-lateral airbladder evaginations occur in many fishes.

c. Anterior Intestinal or Pyloric Area

The anterior intestinal area of the primitive gut, immediately caudal to the stomach region, is characterized by a tendency to form diverticula. Various types of outgrowths occur here, the most constant of which are the hepatic (liver) and the pancreatic evaginations. In lower vertebrates, such as teleost, ganoid, and some elasmobranch fishes, blind digestive pockets, the pyloric ceca, may be formed in this area.

d. Junction of Midgut and Hind gut

At the junction of the developing small and large intestin \s, outgrowths are common in many of the higher vertebrates. The diverticula which occur here



Fig. 280. Morphogenesis of the digestive tract in the frog, Rana pipiens. (See Chap. 10.)

may be large and pouch-like, as in certain mammals, or slender and elongated, as in birds.

e, Cloacal and Proctodaeal Area

The most prominent cloacal diverticula occur ventrally. Ventral urinary bladders arise in this area in many vertebrates. The allantoic diverticulum (Chap. 22) is a prominent outgrowth of the ventral wall of the cloaca. In the chick, the bursa of Fabricius projects dorsally from the area between the cloaca proper and the proctodaeum. Dorsal urinary bladders occur in fishes, arising as dorsal diverticula within this general area. The anal glands of certain mammals, such as the dog, represent proctodaeal evaginations.

B. Development of the Digestive Tube or Metenteron

The following descriptions pertain mainly to the developing shark, frog, chick, and human embryos. Other forms are mentioned incidentally to emphasize certain aspects of digestive-tube development.

1. General Morphogenesis of the Digestive Tube

The general morphological changes of the developing digestive tubes of the shark, frog, chick, and human are shown in figures 279-282.



2. Histogenesis and Morphogenesis of Special Areas a. Oral Cavity

1) General Characteristics of the Stomodaeal Invagination. The oral cavity arises as a simple stomodaeal invagination in most vertebrates. However, in the toadfish, Opsanus (Batrachus) tau, two stomodaeal invaginations occur which later fuse to give origin to a single oral cavity (Platt, 1891). In Amphioxus, the mouth originates on the left side of the head as shown in figure 249D and F; later, it migrates ventrally to a median position. In cyclostomes, the original invagination becomes partly everted secondarily, so that the pituitary invagination eventually lies on the upper portion of the head (fig. 283A, B).

2) Rudiments of the Jaws. In the shark embryo, the mandibular visceral arches bend to form U-shaped structures on either side of the forming oral cavity and thus give origin to the primitive framework of the upper and lower jaws (fig. 253). This condition holds true for other lower vertebrates, including the Amphibia. In the chick, the mandibular arch bends similarly to that in the shark embryo, but only the proximal portion of the upper jaw is present. The anterior or distal portion is displaced by mesenchyme from the head area (fig. 240). The latter condition is true also of the mammals (fig. 261). Regardless of whether or not all the jaw framework on either side of the forming oral cavity is derived from the original mandibular arch, the fact remains that in the formation of the jaws, a U-shaped, mesenchymal framework on either side is established in all the gnathostomous or jaw-possessing vertebrates.

3) Development of the Tongue. <{rhe “tongue” of the shark is essentially a fold of the oral membrane of the floor of the mouth, which overlies the basal (hypobranchial) portion of the hyoid visceral arch) A true, flexible tongue, however, is never developed in the shark or other fishes. Flexible, protrusile tongues are found almost entirely in forms which inhabit the land, where they are used for the acquisition and swallowing of food. The protrusile tongue, therefore, is a digestive-tract structure primarily, and its use in communication in the human and other species is a secondary adaptation.

( The tongue generally develops from folds or growths, associated with the floor of the oral cavity and anterior branchial region.') These lingual growths are associated with the ventral or lower jaw portions of the hyoid and mandibular visceral arches and the ventral area between these arches. However, in the frog, the tongue arises from a mass of tissue at the anterior portion of the floor of the mouth between the mandibular visceral arches. It is protruded from the oral cavity largely by the flow of lymph into the base of the tongue.

^The tongue of the chick and other birds is developed as a fleshy, superficially cornified structure, overlying the anterior portion of the greatly modified hyoid apparatus. It arises from the tuberculum impar, a swelling located in the floor of the pharyngeal area between the first and second visceral arches]



Fig. 281. Morphogenesis of the gut structures in the chick, Callus (domesticus) gallus.

and the copula protuberance which forms as a result of swellings on the lower ends of the second and third visceral arches and the intervening area. The copula forms the root of the tongue; the tuberculum impar contributes the middle portion; and the anterior part of the tongue arises from folds which grow forward from the anterior portion of the tuberculum impar (fig. 284).



(in the human and pig embryos, the anterior portion or body of the tongue arises through the fusion of two ventro-medial swellings of the mandibular arches (fig. 285B). The root of the tongue takes its origin from areas of elevated tissue upon the ventral ends of the hyoid arches and in the adjacent area between the hyoid and first branchial visceral arches (fig. 285B). This elevated tissue is known as the copula. A small, insignificant area, the tuberculum impar, emerges from the medio-ventral area between the mandibular and hyoid visceral arches (fig. 285B). Stages in tongue development in the human embryo are shown in figure 285A-E.

4) Teeth: a) General Characteristics. Teeth are of two types:

( 1 ) horny teeth and

(2) bony or true teeth.

yHorny teeth are found in cyclostomatous fishes, the larval stages of frogs and toads, and in the prototherian mammal, Ornithorhynchus.

Most vertebrates possess true or bony teeth, although they are absent in some fishes (e.g., the sturgeon, pipefishes, and sea horses), turtles, and birds. Among the mammals, certain whales lack teeth, and, in Ornithorhynchus, vestigial bony teeth are formed before hatching, to be lost and supplanted by cornified epidermal teeth. Teeth are lacking also in the edentates, Myrmecophaga and ManLs^

True or bone-like teeth have essentially the same general structure in all vertebrates. A tooth possesses three general areas (fig. 286E):

( 1 ) crown,

(2) neck, and

(3) root.

The crown projects from the surface of epithelium overlying the jaw or oral cavity, while the root is attached to the jaw tissue. The neck is the restricted area lying between the root and the crown.

Teeth generally are composed of two substances, enamel and dentine. Some teeth, however, lack enamel. Examples of the latter are the teeth of sloths and armadillos. The tusks of elephants also represent greatly modified teeth without enamel. Some teeth have the enamel only on the anterior aspect, such as the incisors of rodents.

Teeth may be attached to the jaw area in various ways. In sharks, the teeth are embedded in the connective tissue overlying the jaws (fig. 287F), whereas in most teleosts, amphibia, reptiles, birds, and mammals, they are connected to the jaw itself (fig. 287A-D). In many vertebrates, such as crocodilians and mammals, the tooth is implanted in a socket or alveolus within the jaw tissue (fig. 287C, D). In other forms, the tooth is fused (i.e., ankylosed) to the upper surfaces of the jaw (fig. 287 A, B). A tooth inserted within a socket or alveolus of the jaw is spoken of as a thecodont tooth, while those teeth





liver bud rW

AREA fe'/:







head region






Fig. 282. Morphogenesis of the digestive tract in the human. Observe differentiation of the cloaca in E-G, and the mesenteric supports including the omental bursa in G. (Based upon data from various sources.)




Fig. 283. Partial eversion of the oral cavity during development in the embryo of Petromyzon. (Left) Longitudinal section of the head region in 19-day embryo. (Redrawn and modified from Kingsley, 1912, Comparative Anatomy of Vertebrates, Blakiston, Phila.) (Right) Median longitudinal section of head region of adult Petromyzon. (Redrawn and modified from Neal and Rand, 1936, Comparative Anatomy, Blakiston, Phila.)

fused to the surface of the jaw are referred to either as acrodont or pleurodont teeth. If the tooth is ankylosed to the upper edge of the jaw, as in many teleosts and snakes, it falls within the acrodont group (fig. 287B), but if it is attached to the inner surface of the jaw’s edge, as in the frog and Necturus, it is of the pleurodont variety (fig. 287A).

In most vertebrates, all the teeth of the dentition are similar and thus form a homodont dentition. In some teleosts, some reptiles, and in most mammals, the teeth composing the dentition are specialized in various areas. Such localized groups of specialized teeth within the dentition assume different shapes to suit specific functions. Consequently, the conical, canine teeth are for tearing; the incisor teeth are for biting or cutting; and the flat-surfaced, lophodont and bunodont teeth are for grinding and crushing. A dentition composed of teeth of heterogeneous morphology is a heterodont dentition.

b) Development of Teeth in the Shark Embryo. The development of teeth in the shark embryo is identical with that of the placoid scale previously described. However, the teeth of the shark are larger and more durably constructed than the placoid scale and they are developed from a dental lamina of epithelial cells which grows downward along the inner aspect of the jaw. From this epithelium, a continuous series of teeth is developed as indicated in figure 287E and F. Within the oral cavity and pharyngeal area, ordinary placoid scales are found. Teeth are continuously replaced throughout life in the shark from the dental lamina. The word poiyphyodont is applied to a condition where teeth are replaced continuously.

c) Development of Teeth in the Frog Tadpole. The mouth of the frog tadpole possesses prominent upper and lower lips (fig. 287H). Inside these lips are rows of horny epidermal teeth. Three or four rows are inside the upper lip, and four rows are found inside the lower lip. These horny teeth represent cornifications of epidermal cells. They are sloughed off and



Fig. 284. Development of the tongue in the chick embryo.

replaced continuously until the time of metamorphosis when they are dispensed with. The permanent teeth begin to form shortly before metamorphosis from an epithelial ridge (dental lamina) which grows inward into the deeper tissues around the medial portion of the upper jaw. The teeth develop from an enamel organ and dental papilla in a manner similar to that of the developing shark or mammalian tooth. After the young tooth is partially formed, it moves upward toward the jaw, where its development is completed and attachment to the jaw occurs. Teeth are replaced continuously during the life of the frog.

d) Development of the Egg Tooth in the Chick. Modern birds do not develop teeth. However, an ingrowth of epithelium does occur which suggests a rudimentary condition of the dental lamina of the shark, amphibian, and mammalian embryo (fig. 2871). It is possible that this represents the rudiment of a basic condition for tooth development, one which is never realized, for the sharp edge of the horny beak takes the place of teeth. The egg tooth is a conical prominence, developed upon the upper anterior portion of the upper horny jaw (fig. 287J). It is lost shortly after hatching. It appears to function in breaking the shell at hatching time.

e) Development of Teeth in Mammals. As the oral cavity in the pig or



1 the human embryo is formed, the external margins or primitive jaw area of he oral cavity soon become differentiated into three general areas (fig. 288A) :

(1) an external marginal elevation, the rudiment of the labium or lip,

(2) slightly mesial to the lip rudiment, a depressed area, the labial or abiogingival groove, and

(3) internal to this epithelial ingrowth, the gingiva or gum elevation.

The latter overlies the developing jaw. From the mesial aspect of the labial roove, an epithelial thickening forms which pushes inward into the tissue of he gum or gingiva. This thickened ridge of epithelium forms the dental amina (ledge). (See fig. 288B, C.)

After the dental ledge is formed, epithelial buds arise at intervals along the sdge. These epithelial buds form the rudiments of the enamel organs. Each namel organ pushes downward into the mesenchyme of the gum and evenâ–¡ally forms a cup-shaped group of cells, enclosing a mass of mesenchyme,

Fig. 285. Development of the tongue in the human embryo. (A~D drawn and modified from Ziegler models. (A) Fourth week. (B) About fifth week. (C) 6th to 7th week; 1C mm. (D) 7th week; 14 mm. (E) Adult condition. Observe that the mandibular lingual swellings give origin to the body of the tongue, while the copula forms the root af the tongue.

ORAL epithelium

Fio. 286. Development of thecodont teeth. (A) Early stage of developing premolar of human. (B) Cellular relationships of tooth-forming area greatly magnified. (C) Later stage in tooth development showing dental sac. (D) Vertical section of erupting milk tooth. (E) Vertical section of canine tooth, in situ. (Redrawn and modified from Morris, 1942, Human Anatomy, Blakiston, Phila. After Toldt.)




the dental papilla (fig. 288D, E). The enamel organ differentiates into three layers (fig. 28 8E):

( 1 ) an inner enamel layer, surrounding the dental papilla,

(2) an outer enamel layer, and

(3) between these two layers, a mass of epithelial cells, giving origin to

the enamel pulp.

The cells of the enamel pulp eventually form a stellate reticulum.

Development thus far serves to establish the basic mechanisms for tooth development. Further development of the tooth may be divided into two phases:

(1 ) formation of the dentine and enamel and

(2) development of the root of the tooth and its union with the alveolus or socket of the jaw.

The initial phase of tooth formation begins when the inner cells of the inner enamel layer of the enamel organ become differentiated into columnar epithelial cells. These cells form the amcloblasts (fig. 288E, F). Following this change in the cells of the inner enamel layer, the mesenchymal cells, facing the ameloblasts, become arranged into a layer of columnar odontoblasts (fig. 288F). The odontoblasts then begin to deposit the dentine of the tooth. The initial phase of formation of dentine consists first in the elaboration of an organic substance or matrix. The organic matrix then becomes impregnated with inorganic calcareous materials to form the dentine, a hard, borie-like substance. As the dentinal layer becomes thicker, the odontoblasts recede toward the dental pulp of the papilla. However, the odontoblasts do not withdraw entirely from the dentine already formed, as elongated, extremely fine extensions from the odontoblasts continue to remain within the dentine to form the dentinal fibers (fig. 286B).

Dentine is deposited by the odontoblasts; the ameloblasts deposit the enamel layer in the form of a cap, surrounding the dentine (fig. 286A, B). In doing so, a slight amount of organic substance is first deposited, and then the ameloblast constructs in some way a prismatic column of hard calcareous material at right angles to the dentinal surface (fig. 286B). The columnar prisms thus deposited around the dentine form an exceedingly hard cap for the dentine. As in the formation of the dentine, the elaboration of enamel begins at the crown or distal end of the tooth and proceeds rootward.

The development of the root of the tooth and its union with the jaw socket (alveolus) is a complicated procedure. This phase of tooth development is accomplished as follows: The mesenchyme, with its contained blood vessels and nerves of the dental papilla, lies within the developing dentinal layer of the forming tooth. At the base of the tooth (i.e., the end of the tooth opposite the crown), the mesenchyme of the dental papilla is continuous with



dental ledge



Fig. 287. Tooth development and arrangement in various vertebrates. (A-D) Tooth relationships with the jaw. (Redrawn and modified from Rand, 1950, The Chordates, Blakiston, Phila. After Wilder.) (E) Dental ledge and developing teeth in the dog shark, Acanthias. (Redrawn and modified from Rand, 1950, The Chordates, Blakiston, Phila. After Kingsley.) (F) Section of the shark’s lower jaw indicating a continuous replacement of teeth, i.e., a polyphyodont condition. (Redrawn and modified from Rand, 1950, The Chordates, Blakiston, Phila.) (G) Incisor tooth of rodent. (Redrawn and modified from Rand, 1950, The Chordates, Blakiston, Phila. After Zittel.) (H) Horny teeth of 12 mm. frog tadpole. (I) Rudimentary dental lamina in upper jaw of chick. (Redrawn from Lillie, 1930, The Development of the Chick, Holt & Co., N. Y.) (J) Anterior

portion of upper jaw of 18-day chick showing egg tooth.

the mesenchyme surrounding the developing tooth. Around the base, sides, and crown of the tooth, this mesenchyme condenses and forms the outer and inner layers of the dental sac (fig. 286C). The latter is a connective-tissue sac which surrounds the entire tooth, continuing around the outside of the outer enamel cells of the enamel organ. As the dentine and enamel are de



posited, the process of deposition proceeds downward from the crown "oward the developing root of the tooth. However, in the root area, the cellular layers of the enamel organ are compressed against the dentine, where they form the epithelial sheath. The sheath eventually disintegrates and disappears. The formation of enamel thus becomes restricted to the upper or crown part of the tooth, the root portion consisting only of dentine. As the root area of the tooth lengthens downward, the tooth as a whole moves upward. Finally, the crown of the tooth erupts to the outside through the tissues of the gum (fig. 286D). The eruption, completion, and shedding of the milk or deciduous teeth in the human body occur apparently as shown in the following table.

The Milk Dentition

Median incisors Lateral incisors First molars Canines Second molars

6th to 8th month 8th to 12th month 12th to 16th month 17th to 20th month 20th to 24th month

The Permanent Dentition

First molars Median incisors Lateral incisors First premolars Second premolars Canines Second molars Third molars

7th year 8th year 9th year 10th year 11th year 13 th to 14th year 13th to 14th year 17th to 40th year

This table is taken from McMurrich, J. Playfair. 1922. Keibel and Mall, Manual of Human Embryology, page 354, Lippincott, Philadelphia.

At about the time of eruption, the tooth becomes cemented into the alveolus or socket of the jaw in the following manner:

( 1 ) The inner layer of the dental sac (fig. 286D) forms a layer of cementoblasts which deposit a coating of cementum over the dentine of the root (fig. 286E). This occurs only after the epithelial sheath (enamellayer cells around the root) has been withdrawn or otherwise has disappeared.

(2) The cells of the outer layer of the dental sac become active in forming spongy bone.

(3 ) As the tooth reaches maturity, the two bony surfaces, i.e., the cementum of the root and the spongy bone of the jaw socket, gradually begin to approach each other. Then, as more cementum is deposited and more spongy bone is formed, the space between the cementum and the spongy bone of the alveolus becomes extremely narrow (fig. 286E).



(4) Finally, the dental-sac tissue between these two bony surfaces forms the peridental membrane, a thin, fibrous, connective-tissue layer whose fibers are attached to the cementum and to the spongy bone of the socket. In other words, the cemental bone of the root and the spongy bone of the socket become sutured together by means of the interlocking fibers of the peridental membrane. This type of suture, which







Fig. 288. Tooth development in the pig. (A) Upper and lower jaw region of 18 mm. pig embryo showing labial and gum areas with the labial groove insinuated between. (B) Section through snout and upper and lower jaws of 30-mm. pig embryo showing formation of nasal passageways, secondary palate, lip, gum, and jaw regions, and ingrowing dental ledge. (C) High-powered drawing of dental ledge shown in square C in figure B. (D) Section similar to B in 65-mm. pig embryo. (E) Enlargement of area marked E in D showing dental papilla and enamel organ. (F) Drawing showing juxtaposition of inner layer of enamel organ (the an^eloblast layer) and the odontoblast cells which differentiate from the mesenchyme of the dental papilla.



Fig. 289. Palatal conditions in frog, chick, and mammal. (A) Frog, adult. (B) Chick, 16-day embryo. (C) Human adult. (Redrawn and modified from Morris, 1942, Human Anatomy, Blakiston, Phila.) Only the anterior or hard palate is supported by bone, the soft palate being a fleshy continuation of the palate caudally toward the pharyngeal area. (D-F) Stages in development of the palate in the pig. (D) 20.5 mm. (E) 26.5 mm. (F) 29.5 mm.

is formed between the root of the tooth and the walls of the alveolar socket, is called a gomphosis (fig. 286E).

The permanent teeth, which supplant the deciduous teeth, develop in much the same manner as the deciduous teeth. Man, like the majority of mammals, develops two sets of teeth and, consequently, is diphyodont. Some mammals, such as the mole, Scalopus, never cut the permanent teeth, while the guinea pig sheds its deciduous teeth in utero.

5) Formation of the Secondary Palate. In the fishes and the amphibia, a secondary palate, separating the oral cavity from an upper respiratory passageway, is not formed. The formation of a secondary palate begins in the turtle group and is well developed in the crocodilians and mammals. The bird also



has a secondary palate, but it is built more tenuously than that of the crocodilian-mammalian group (fig. 289 A-C).

During secondary-palate formation in the mammal, the premaxillary, maxillary, and palatine bones develop secondary plate-like growths which proceed medially to fuse in the midline (fig. 289D-F). The secondary palate thus forms the roof of the oral cavity — the air passageway from the outside to the pharynx being restricted, when the mouth is closed, to the area above the secondary palate.

^ 6 ) Formation of the Lips. Lips are ridge-like folds of tissue surrounding the external orifice of the oral cavity. They are exceptionally well developed in mammals, where they are present in the form of fleshy mobile structures'^ They are absent in the prototherian mammal, Ornithorhynchus, as well as in birds and turtles, where the horny edges of the beak displace the fleshy folds at the oral margin. Lips are much reduced in sharks, where the toothed jaws merge with the general epidermis of the skin, but arc present in most fishes, amphibia, and most reptiles. In general, lips are immobile or only slightly mobile structures in the lower vertebrates, although in some fishes they possess a mobility surpassed only in mammals.

In the formation of the lips, a labial groove or insinking of a narrow ledge

Fig. 290. Oral glands. (A) Poison and labial glands of the rattlesnake, Crotalus horidus. (Redrawn from Kingsley, 1912, Comparative Anatomy of the Vertebrates, Blakiston, Phila.) (B) Loci of origin of salivary glands in human embryo. (Redrawn from Arey, 1946, Developmental Anatomy, Saunders, Phila.) (C) Position of mature salivary glands in human. (Redrawn and modified from Morris, 1942 Human Anatomy, Blakiston, Phila.) ^



Fig. 291. Diagrams of intestinal tracts in various fishes. (Redrawn from Dean, 1895, Fishes, Living and Fossil, Macmillan. N. Y.) (A) Petromyzon, the cyclostome. (B)

Protopterus, the lungfish. (C) The shark.

of epidermal cells occurs along the edge of the forming mouth. The labial groove then divides the edge of the forming mouth into an outermost lip margin and the gum or jaw region (fig. 288A). In forms where the lip is mobile, the lip region becomes highly developed and the muscle tissue which invades this area comes to form the general mass of the lip.

7) Oral Glands. Mouth glands arc present throughout the vertebrate series. Mucus-secreting glands are the predominant type, but specialized glands, producing special secretions, appear in many instances. The cyclostomatous fish, for example, possesses a specialized gland which secretes an anticoagulating substance to prevent coagulation and stoppage of blood flow in the host hsh to which it may be temporarily attached by its sucker-like mouth. Meanwhile, it rasps the host’s flesh with its horny teeth and “sucks” the flowing blood. Salivary glands (i.e., glands forming the saliva) make their appearance in the amphibia. Such glands may be found on the amphibian tongue, where, as lingual glands, they secrete mucus and a watery fluid. Intermaxillary glands are present on the amphibian palate. The poison glands of the Gila monster and of snakes represent specialized oral glands (fig. 290A). Salivary glands are present also below the tongue and around the lips and palate in snakes. Birds, in general, possess salivary glands of various sorts. The mammals are characterized by the presence of highly developed, salivary glands, among which are the parotid, sublingual, and submaxillary glands. Unlike most of the salivary glands in other vertebrates, the mammalian salivary glands, in many species, secrete mucus and a watery fluid, together with a starch-splitting enzyme, ptyalin.

I^^The submaxillary and sublingual glands in mammals arise as evaginations of the oral epithelii n in the groove between the forming lower jaw and the



Fig. 292. Developing stomach regions of the digestive tract. (A-C) Three stages in the development of the pig’s stomach. Arrows indicate formation of omental bursa which forms from the pocket-like enlargement of the dorsal mesogastrium and proceeds to the left forming the omental bursa as the pyloric end of the stomach rotates toward the right. The ventral aspect of the stomach is indicated by crosses. (D) Diagram of the ruminant stomach. The abomasum corresponds to the glandular stomach of the pig or human; the other areas represent esophageal modifications. (Redrawn from Kingsley, 1912, Comparative Anatomy of the Vertebrates, Blakiston, Phila.)

developing tongue. The place of origin is near the anterior limits of the tongue. Two of these epithelial outpushings occur on either side (fig. 290B). The submaxillary-gland and sublingual-gland ducts open at the side of the frenulum of the tongue (fig. 290C). The parotid glands arise as epithelial evaginations, at the angle of the mouth, from the groove which separates the forming jaw and the lip (fig. 290B, C).

The various oral glands, such as the palatine, labial, tongue, and cheek glands of mammals and lower vertebrates, the poison glands of snakes, etc., arise as epithelial buds which grow out from the developing oral cavity in a manner similar to those of the parotid, submaxillary, and sublingual glands of mammals. The original epithelial outgrowths may branch and rebranch many times to produce large, compound, alveolar glands, as in the parotid, submaxillary, and sublingual glands of mammals and the poison glands of snakes.

b. Development of the Pharyngeal Area

1) Pharyngeal Pouches and Grooves. The pharynx is that region of the early digestive tube which lies between the oral cavity and the esophagus. In adult vertebrate species, the pharyngeal area is much modified and differentially developed. However, in the early embryo, it tends to assume a generalized sameness throughout the vertebrate series.

( The early formation of the pharynx results from a series of outpocketings of the entoderm of the foregut, associated with a corresponding series of epidermal inpushings; the latter tend to meet the entodermal outgrowthsr^s a result of these two sets of movements, the one outward and the other inward, the lateral plate mesoderm becomes isolated into dorso-ventral columns, the branchial or visceral arches, between the series of outpocketings and inpush



ings (figs. 252F; 260; 262). The entodermal pouches or outpocketir gs are called the branchial, pharyngeal, or visceral pouches, while the epidermal (ectodermal) inpushings form the visceral or branchial grooves (furrows). The mesodermal columns constitute the visceral arches?^

The number of branchial pouch-groove relationships, thus established, varies in different vertebrate species. In the cyclostomatous fish, Petrornyzon, there are seven; in Squalus acanthias, the shark, there are six. The latter number is present typically in a large number of fishes. In most frogs and salamanders, there are five, pouch-groove relationships with a vestigial sixth; in the chick, pig, and human, there are four. (In reptiles, birds, and mammals, the fourth pouch on either side may represent a fusion of two or three pouches.) The number of visceral arches, of course, varies with the number of pouch-groove relationships produced, the first pair of arches being formed just anterior to the first pair of pouches. The first pair of arches are called the mandibular visceral arches; the second pair constitute the hyoid visceral arches; and the remaining pairs form the branchial arches.

Within each visceral arch, three structures tend to differentiate:

( 1 ) a skeletal arch,

(2) a muscle column, associated with the skeletal arch, and

(3) the aortal arch, a blood vessel.

In all water-living vertebrates, including those species which spend the larval period in the water, the entoderm of the branchial pouch and ectoderm of the branchial groove tend to fuse intimately and perforate to form the branchial or visceral clefts, with the exception of the first, pouch-groove relationship. The latter is variable. In the amphibia, the first pouch does not perforate but becomes associated with the developing ear. In land forms, on the other hand, the pouches, as a rule, remain imperforate or weakly so. As a rule, they continue unperforated in mammals. The ectoderm and entoderm of the branchialpouch-groove relationships is very thin in the chick, and openings (?) may appear in the more anterior pouches. (Note: The relation of these pouches to respiration is discussed in the following chapter.)

2) Pharyngeal Glands of Internal Secretion. An important developmental function of the pharynx is the formation of masses of epithelial cells from various parts of the entodermal wall which serve as endocrine glands. These glands are the thyroid, parathyroid, thymus, and ultimobranchial bodies. The places of origin of these cellular masses and their part in the formation of the endocrine system are discussed in Chapter 21.

3) Other Respiratory Diverticula. One of the primary functions of the pharyngeal area is respiration. In most water-living vertebrates, the pharyngeal pouches are adapted for respiratory purposes. However, in many water-dwelling species and in all land forms, a median ventral outpushing occurs which de

Fig. 293. Characteristics of the mucous membrane in different regions of the human digestive tract: (A and D) redrawn and modified from Maximow and Bloom, A Textbook of Histology, Saunders, Philadelphia; (B and C) redrawn from Bremer, A Textbook of Histology, Blakiston, Philadelphia. (A) Esophageal area. Stratified squamous epithelium together with esophageal and cardiac glands are characteristic. The esophageal glands are located in the submucous layer and are of the tubulo-alveolar variety. The cardiac glands are found in the upper and lower esophageal regions and are confined to the mucous layer. (B) Stomach region. The mucous layer of the stomach is featured by the presence of many glands composed of simple and branched tubules. These glands open into the bottom of the gastric pits which in turn form small, circular openings at the mucosal surface. (C) The mucosal walls of the small intestine present many finger-like processes, the villi, between the bases of which the intestinal glands or crypts of Lieberkuhn project downward toward the lamina muscularis mucosae. (D) The mucosa of the large intestine is devoid of villi, and the glands of Lieberkuhn are longer and straighter than in the small intestine.




velops into the lungs or into structures which function as air bladders and lungs. (See Chap. 14.)

c. Morphogenesis and Histogenesis of the Esoj)hagus^and the Stomach Region of the Metenteron

The esophageal and stomach areas of the gut develop from that segment of the foregut which extends from the pharyngeal area caudally to the area of the developing gut tube from which the liver and pancreatic diverticula arise. In Arnphioxus and certain of the lower vertebrates, a true stomach is not differentiated within this portion of the foregut. This condition is found in the cyclostome, Petromyzon, in the lungfish, Protopterus, and various other forms (fig. 291 A, B). In these species, this segment of the gut merely serves to transport food caudally to the intestine, and the histogenesis of its walls resembles that of the esophagus. On the other hand, a true stomach is developed in all other vertebrate species. The funetions of the stomach are to store food, to break it up into smaller pieces, and to digest it partially. As such, the stomach comprises that segment of the digestive tract which lies between the esophagus and intestine. It is well supplied with muscular tissue, is capable of great distentioUp and possesses glands for enzyme secretion.

In development, therefore, the foregut area between the primitive pharynx and the developing liver becomes divided into two general regions in most vertebrates:

( 1 ) a more or less constricted, esophageal region, and

(2) a posteriorly expanded, stomach segment (figs. 279-282).

The latter tends to expand and to assume a general, V-shaped form, the portion nearest the esophagus comprising the cardiac region, and the part nearest the intestine forming the pyloric end.

Many variations in esophageal-stomach relationships are elaborated in different vertebrate species. In the formation of the stomach of the pig or human, for example, a generalized, typical, vertebrate condition may be assumed to exist. In these forms, the stomach area of the primitive gut gradually enlarges and assumes a broad, V-shaped form, with its distal or pyloric end rotated toward the right (fig. 292A-C). Eventually, the entodermal lining tissue shows four structural conditions:

(a) There is an esophageal area near the esophagus, where the character of the epithelial lining resembles that of the esophagus.

(b) A cardiac region occurs, where the epithelium is simple, columnar in form, and contains certain glands.

(c) There is a fundic region, capable of being greatly expanded. The internal lining of the fundic area produces numerous, simple, slightly branehed, tubular glands, wherein pepsin is secreted by the chief cells and hydrochloric acid by the parietal cells (fig. 293).



(d) The pyloric area is the last segment of the stomach and is joined to the intestine. It has numerous glands, producing a mucus-like secretion.

The pig’s stomach resembles closely that of the human.

If we compare the general morphogenesis of the stomach in the pig or human with that of the shark, frog, chick, or the cow, the following differences exist.

The shark stomach is composed mainly of fundic and pyloric segments (fig. 279C). The stomach of the frog closely resembles that of the pig (fig. 280F). Unlike the pig, however, the frog is able to evert the stomach by muscular action projecting it forward through the mouth to empty its contents. In the chick (fig. 28 IE), an area of the esophagus expands into a crop which functions mainly as a food-storage organ. A glandular stomach (proventriculus), comparable to the fundus of the pig, is formed posterior to the crop, while, still more caudally, a highly muscular gizzard or grinding organ is elaborated.

In the cow or sheep, an entirely different procedure of development produces a greatly enlarged, distorted, esophageal portion of the stomach. This esophageal area of the stomach comprises the rumen, the reticulum or honeycomb stomach, and the omasum (psalterium) or manyplies stomach. The distal end of the stomach of the cow or sheep is the abomasum or true stomach, comparable to that of the human or pig described above (fig. 292D).

d. Morphogenesis and Histogenesis of the Hepato-pancreatic Area

The hepato-pancreatic area of the digestive tract is a most important one. Its importance springs not only from the development of indispensable glands but also from the relationship of the liver to the developing circulatory system (Chap. 17) and the division and formation of the coelomic cavity. (See Chap. 20.)

1) Development of the Liver Rudiment. The liver begins in all vertebrates as a midventral outpushing of the primitive metenteron, immediately caudal

Fig. 294. Development of the liver and pancreatic rudiments. (Diagrams CT, redrawn from Lillie, 1930, The development of the chick. Holt, N. Y. F redrawn from Thyng, 1908, Am. J. Anat.) (A) Developing liver rudiment in 10 mm. embryo of the dogshark, Squalus acanthias. (B) Developing liver in tadpole of Rana pipiens. (See also Figs. 221, 223, 225, 280.) (C) Developing liver rudiments in the 3rd-day

chick. (D) Developing liver in early 4th-day chick. (E) Developing liver in late 4th-day chick. (F) Hepatic evagination in 7.5 mm. human embryo. (G) Relation of the fully developed liver to associated structures in various vertebrates. (Gl) Squalus acanthias. The liver is suspended from the posterior surface of the septum transversum by the coronary ligament. (G2 and G3) Frog, Rana pipiens. G2 transverse view; G3 sagittal view. (G4 and G5) 16-20 day chick. Callus domesticus. G4 transverse view. Observe that the liver lobes and peritoneal cavity have grown forward on either side of the heart and have separated the heart and pericardial cavity from the ventro-lateral body walls. G5 is a left ventral view of the heart, pericardial cavity, and liver. Left lobe of the liver is removed. Observe that the septum transversum is applied to the posterior wall of the parietal pericardium. G6 Mammal. The septum transversum has been completely displaced by developing diaphragmatic tissue. The liver is suspended from the caudal surface of the diaphragm by the coronary ligament.


left liver LOBE





Fig. 294. (See facing page for legend.)




to the Stomach. It originates thus between the foregut and midgut areas of the developing digestive tube.

a) Shark Embryo. In the 10- to 12-mm. shark embryo, Squalus acanthias, the liver rudiment arises as a midventral evagination of the gut which pushes downward and forward between the two parts of the ventral mesentery. It soon becomes divisible into three chambers, viz., a midventral chamber, the rudiment of the gallbladder, and two lateral chambers, the fundaments of the right and left lobes of the liver (figs. 279B; 294A).

b) Frog Embryo. In the frog, the liver rudiment appears as a ventrocaudal prolongation of the foregut area at the early, neural fold stage (figs. 220B; 223B). Later, the anterior end of the hepatic rudiment differentiates into the liver substance in close relation to the vitelline veins as the latter enter the heart, while the posterior extremity of the original hepatic rudiment differentiates into the gallbladder (figs. 280; 294B, G2, G3).

c) Chick Embryo. In the chick, two evaginations, one anterior and the other posterior, arise from the anterior wall of the anterior intestinal portal, beginning at about 50 to 55 hours of incubation (fig. 294C). These evaginations project anteriorly toward the sinus venosus of the heart, where they eventually come to surround the ductus venosus as it enters the sinus. (See Chap. 17.) At the end of the fourth day of incubation, secondary evaginations from the two primary outgrowths begin to produce a basket-like mass of tubules which surround the ductus venosus (fig. 294E). The gallbladder arises from the posterior hepatic outpushing toward the end of the third day of incubation (fig. 294D).

d) Pig Embryo. The liver diverticulum in the 4- to 5-mm. embryo of the pig begins as a bulbous outpushing of the foregut area, immediately caudal to the forming stomach (fig. 295E). This outpushing grows rapidly and sends out secondary evaginations, including the vesicular gallbladder. The latter is already a prominent structure in the 5. 5-mm. embryo (fig. 295A).

Fig. 295. Development of liver and pancreatic rudiments (Continued). (A) Diagram of early hepatic diverticulum in pig embryo of about 5.5 mm. (Redrawn and modified greatly from Thyng, 1908, Am. J. Anat.) For early growth of liver in pig, see Figs. 261A and 262. (B) Hepatic ducts, hepatic tubules, and hepatic canaliculi in relation to blood

sinusoids. It is to be observed that the common bile duct ( 1 ) gives off branches, the hepatic ducts (2), from which arise the branches of the hepatic duct (3) which are continuous with the hepatic tubules or hepatic cord cells (4). Compare with Fig. 295C. (C) A

portion of liver lobule of human. (Redrawn and modified from Maximow and Bloom, A Text-book of Histology, Saunders, Phila.) Blood sinusoids are shown in black; liver cells in stippled white; bile canaliculi shown in either white or black. (D) Section showing three pancreatic diverticula in 5-day chick embryo. (Redrawn from Lillie, 1930, The development of the chick, Holt, N. Y. After Choronschitsky.) (E) Pancreatic diverticula in 5.5 mm. pig embryo. (Redrawn from Thyng, 1908, Am. J. Anat. 7.) (F)

Pancreatic diverticula in 20 mm. pig embryo. (Redrawn from Thyng, 1908, Am. J. Anat. 7.) (G) Pancreatic acini and islet of Langerhans.



Fig. 296. Development of coils in the digestive tracts in the dog shark, Squalus acarithias, and in the frog, Rana pipiens. (A) Squalus acanthias embryo of 110 mm. (B-F) Rana pipiens, digestive tube development, shown from ventral aspect. Arrows in B and C denote primary movements of the primitive gut tube resulting in condition shown in D.

e) Human Embryo. In the human embryo, the liver arises in a similar manner to that of the pig embryo from the ventral wall of the foregut, just posterior to the forming stomach (fig. 294F). The hepatic outpushing invades the area of the ventral mesentery and becomes intimately associated with the substance of the septum transversum (fig. 362H). Secondary evaginations or liver cords ramify extensively within the mesenchyme of the mesentery, and the vitelline or omphalomesenteric veins, as in other vertebrates, become broken up into sinusoids, surrounding the outgrowing hepatic cords. The gallbladder arises as a secondary outgrowth from the posterior wail of the original hepatic outgrowth (fig. 294F). The gallbladder rudiment enlarges distally and gives origin to the cystic duct which joins the common bile duct.

2) Histogenesis of the Liver. As the liver pushes out into the ventral mesen



tery, it tends to project forward below the forming stomach and the caudal limits of the heart (figs. 295A; 362H). Within the ventral mesentery, secondary evaginations or epithelial cords of entodermal cells sprout from the primary entodermal evagination of the entodermal lining of the gut (fig. 295A). These epithelial or liver cords grow in between the paired vitelline veins, and the veins become changed into a mass of capillary-like sinusoids. The liver cords come to lie in the interstices between the vitelline sinusoids (fig. 295B).

As the liver cords grow within the ventral mesentery, mesenchymal cells, given off from the medial surfaces of the mesentery, come to surround the liver cords and give origin to the connective-tissue substance of the liver. The outer surface of the ventral mesentery retains its integrity and functions as the peritoneal covering of the growing liver.

It is apparent that the growth of the epithelial (liver) cords progresses dichotomously, branching into a tree-like system of branches from the original hepatic diverticulum of the gut tube, thus forming the parenchyma of the liver (Bloom, ’26). The proximal portion of the original hepatic diverticulum forms the common bile duct, or ductus cholcdochus, whereas the larger branches of the hepatic cords develop lumina and form the duct system. The gallbladder represents an original diverticulum from the common-bile-duct rudiment. The liver cords appear to be hollow from the beginning. The bile capillaries thus apparently develop directly within the liver cords. The livercord cells probably assume their typical cuboidal shape under the influence of the surrounding young connective tissue and branches from the portal vein (Bloom, ’26). The ultimate relationship between hepatic cell cords, liver sinusoids, and bile ductules is shown in figure 295C.

In the majority of vertebrates, as the liver substance increases within the ventral mesentery below the stomach area, it expands the ventral mesentery enormously until the liver, with its coating of ventral mesentery, fills the coelomic space below the gut tube and posterior to the heart. The developing liver thus comes in contact with the ventral and lateral body walls and becomes fused to these walls. The anterior face of the liver, eventually, forms a partition across the coelomic cavity just caudal to the heart (figs. 261; 295A). The anterior face of the liver substance gradually separates and forms a primitive partition across the body cavity. This partition is the primary septum transversum (fig. 295A). (Sec also Chap. 20.)

As the liver rudiment develops in the pig embryo, the septum transversum forms essentially as described above, i.e., it develops as a modification of the ventral mesentery covering the anterior face of the liver. However, in the human embryo, the primary septum transversum develops precociously, forming a partition across the ventral area of the coelomic cavity between the developing heart and liver (fig. 362F— H). When the hepatic cords in the human embryo grow forward within the ventral mesentery, they secondarily become related to the previously formed, primitive septum transversum along the



caudal aspect of the septum. The ends achieved in the human and pig embryos are much the same, therefore, and the anterior face of the developing liver and the septum transversum are intimately associated.

3) Development of the Rudiments of the Pancreas: a) Shark Embryo. In the embryo of Squalus acanthias, the shark, the pancreas arises as a dorsal diverticulum of the gut a short distance posterior to the gallbladder and hepatic outpushings (fig. 279B). It grows rapidly and, in the 18- to 20-mm. embryo, it is a much-branched gland with its pancreatic duct entering the duodenum slightly anterior to the beginning coils of the spiral valve.

b) Frog Embryo. In the frog, the pancreas arises from three diverticula, one dorsal and two ventral, near the liver rudiment (Kellicott, T3, p. 167). The dorsal diverticulum is solid and separates from the gut tissue. The two ventral diverticula arise together from the ventral portions of the gut but soon branch into two rudiments. As these rudiments enlarge and branch, they eventually unite with the dorsal diverticulum of the pancreas, and the three fuse to form one gland. The proximal portion of the original, ventral, pancreatic outpushing remains as the pancreatic duct and empties into the duodenum close to the bile duct.

c) Chick Embryo. As in the frog, three pancreatic diverticula arise in the

Fig. 297. Developing coils in the digestive tube of the pig. (A) 12 mm. embryo. (B) 24 mm. embryo. (C) 35 mm. embryo. (D) Cecum and large intestine showing coils in 120 mm. embryo. (E) Coiling of large intestine of young adult pig. Observe haustra or lateral diverticula of colonic wall. (All figures redrawn and modified from Lineback, 1916, Am. J. Anat. 16.)







Fig. 298. Structural composition of walls of human digestive tract. (A) Diagrammatic representation of digestive tract structure. (B) Portion of wall of small intestine showing folds of mucosa. (A and B redrawn from Maximow and Bloom, 1942, A Textbook of Histology, Saunders, Phila. B after Braus.)

chick. The dorsal one appears first as an outpushing into the dorsal mesentery at the end of the third and early fourth days of incubation (fig. 295D). The two ventral diverticula arise during the end of the fourth and early fifth days of incubation as two lateral diverticula of the posterior hepatic evaginations close to the latter’s origin from the duodenum. The three diverticula fuse into one pancreatic mass, but tend to retain the proximal portions of the original outpushings as pancreatic ducts. Two or even all three may persist in the adult.

d) Pig Embryo. Two pancreatic diverticula make their appearance in the pig embryo. One, the ventral pancreatic diverticulum, arises from the proximal end of the hepatic evagination, while the other, the dorsal diverticulum, emerges as a separate dorsal outpushing from the duodenal area approximately opposite the hepatic diverticulum (fig. 295E). In the 20-mm. embryo of the pig, these two diverticula proceed in development as shown in figure 295F. At about the 24-mm. stage, the duct of the ventral pancreas is obliterated, the dorsal pancreatic duct (duct of Santorini) remaining ordinarily as the pancreatic duct of the adult (Thyng, ’08).

e) Human Embryo. Dorsal and ventral pancreatic evaginations occur in the human embryo in a manner similar to that in the pig. Both fuse into one mass, although the dorsal pancreas grows much faster and forms much of the bulk of the pancreatic tissue. The ventral pancreas swings dorsally as the stomach and duodenal area of the intestine are rotated toward the right side of the peritoneal cavity. In doing so, the dorsal pancreas appropriates the duct of the ventral pancreas proximaliy toward the intestine, while distally it retains its own duct. This combined duct, or duct of Wirsung, first observed by Wirsung in 1642 (see Lewis, T2), is the pancreatic duct of the adult. Occa



sionally, two ducts opening into the intestine are retained, the original dorsal duct, the accessory duct or duct of Santorini, described by Santorini (see Lewis, ’12), and the duct of Wirsung or ventral pancreatic duct. The latter condition appears to be normal in the dog.

4) Histogenesis of the Pancreas. The original pancreatic diverticula branch, rebranch, and form an elaborate duct system. The secretory portions of the pancreas or the acini arise as terminal outgrowths of the distal portions of the duct system. The pancreas thus is a compound alveolar (acinous) gland. The loose connective tissue of the pancreas forms the surrounding mesenchyme, derived from the mesenteric tissue.

Two types of secretory cells bud off from the developing duct system. The majority form the acini of the pancreatic gland and pour their secretions into the duct system. This constitutes the exocrine aspect of the pancreas. Other cell masses bud off from the duct system and give origin to the islets of Langerhans. The latter form the endocrine portion of the pancreas (fig. 295G) .

/e. Morphogenesis and Histogenesis of the Intestine

1) Morphogenesis of the Intestine in the Fish Group. In the fishes, the intestinal rudiment of the digestive tube does not undergo extensive elongation during development. A relatively short tube is formed as shown in figure 279C, although some coiling of the intestine does occur in teleost fishes. A distinct, small and large division of the intestine is not formed; intestinal and rectal areas only are developed. Specialized rectal outgrowths develop in sharks (fig. 279C), while, in teleost fishes, pyloric evaginations or cecae are formed.

2) Morphogenesis of the Intestine in Amphibia, Reptiles, Birds, and Mammals. The development of the intestine in this group of vertebrates involves considerable elongation and coiling (figs. 280, 281, 282). Two general divisions of the intestine are formed, a small intestine, developed from the midgut portion of the primitive metenteron, and a hindgut or colon, derived from the hindgut portion of the gut tube. A rectal area is formed at the caudal end of the hindgut. There is a tendency also for enlargements or extensions to occur in the area of junction between the small intestine and colon in the birds and mammals.

3) Torsion and Rotation of the Intestine During Development. Twisting and rotation of the stomach and intestine is a general feature of alimentarytract development. In the shark embryo, the stomach is rotated in such a way that its pyloric end is pulled upward toward the liver, forming a J-shaped structure (fig. 296A). Also, the duodenal and valvular areas of the intestine are rotated vertically, and the place of attachment of the dorsal mesentery moves into a ventro-lateral position.

The developing stomach and intestine of the frog embryo presents a remarkable and precise rotative procedure. In the early stages, the primitive metenteron is a simple tube, continuing from the forming stomodaeum caudad



to the proctodaeum (fig. 280B). At the 6- to 7-mm. stage, the stomach-liver area begins to rotate toward the right as indicated in figure 296B. At about 7 to 9 mm., the stomach-liver area is projected to the right and anteriad, while the midgut and hindgut regions move toward the left (see arrows, fig. 296C). At the stage of development when the larvae approximate 10 mm. in length, the stomach and intestinal areas are arranged as in figure 296D. Through the larval stages to the time of metamorphosis, the midgut or small intestinal area becomes greatly extended and coiled as shown in figure 296E. At the time of metamorphosis, the small intestine becomes greatly reduced in relative length (fig. 296F),

The chick embryo manifests similar gastrointestinal torsion. The duodenal area of the intestine and the gizzard are pulled forward toward the liver, while the small intestine becomes coiled and lies to a great extent in the umbilical stalk, to be retracted later into the abdominal area.

At the 10-mm. stage in the pig, the digestive tract consists of a simple tubular structure as shown in figure 297A (Lineback, T6). In this figure, the pyloric-duodenal area is projected forward toward the liver, where the pyloric-duodenal area eventually is tied to the liver on the right side of the peritoneal cavity, with the result that the forming stomach lies transversely across the upper part of the abdominal cavity. The cecal and large intestinal areas are rotated around the small intestine (see arrow, fig. 297A), when the latter lies herniated within the umbilical cord. In figure 297B is shown the condition in the 24-mm. pig. It is to be observed that there is now a half rotation of the large intestine around the small intestine, the latter being considerably coiled, while in figure 297C a complete rotation of 360 degrees is shown.

Aside from these rotational movements, extensive coiling of the gut tube occurs, especially in the higher vertebrates. For example, the small intestine of the frog becomes coiled extensively during the larval period (fig. 296E). Reference to figure 297D and E shows a similar coiling of the large intestine of the pig.

Rotational movements of the intestine in the human embryo also occur. For example, in the human embryo of about 23 mm., a condition is present, comparable to that of the pig embryo of 24 mm., and the future large intestine has been rotated 180 degrees around the small intestine as shown in figure 282F. Unlike the pig, however, a complete rotation of the gut is not effected. Also, the large intestine does not later form into a double coil as in the pig. In the human embryo soon after the intestine is retracted from its herniated position in the umbilical cord (fig. 282G), the cecal area of the large intestine becomes fixed to the right side of the peritoneal cavity near the crest of the ilium (Hunter, ’28). The ascending, transverse, and descending portions of the large intestine are then developed (fig. 364G, H).

4) Histogenesis of the Intestine. During histogenesis of the intestine, two



prominent modifications of the internal lining or mucous membrane tend to occur:

(a) Small finger-like projections or villi are formed which project inwardly into the lumen (fig. 298A); and

(b) the internal lining may project inwardly in the form of extensive elongated folds.

In many fishes, such as the sharks, lungfishes, ganoids, and cyclostomes, elaborate folds of the mucosa, known as the spiral folds or valves, are formed (fig. 29 1C). Similarly, in higher vertebrates, elongated folds may occur, such as the valves of Kerkring in the human and pig small intestine (fig. 298B).

Another conspicuous feature of the early histogenesis of the entodermal layer is the formation of epithelial membranes and plugs. The pharyngeal membrane is formed by the stomodaeal ectoderm and pharyngeal epithelial layers. The proctodaeal membrane is similarly constructed. This structure serves as a temporary blocking device between external and internal media. Under normal conditions these membranes degenerate and disappear, although occasionally they may persist. Epithelial plugs, temporarily obliterating the lumen of the digestive tract, appear with regularity in many vertebrates. Such temporary obstruction, for example, may appear in the developing digestive tract of the chick or in the human esophagus, duodenum, and other areas of the digestive tract.

/. Differentiation of the Cloaca

As previously observed, the caudal end of the intestine expands into the cloaca, an enlarged area which eventually receives the urinary products as well as the intestinal substances. The differentiation of this area is considered in Chapter 18.

C. Physiological Aspects of the Developing Gut Tube

Within the developing digestive tubes of the shark, reptiles, birds, and mammals, a brownish-green, pigmented material appears during the latter phases of embryonic development. This material is composed of cells, bile pigments, mucus, etc. It is discharged during the period just before or after parturition. Fetal swallowing of ammionic fluid, gastrointestinal motility, the presence of enzymes, fetal digestion and absorption, and defecation are wellestablished facts in the physiology of the developing digestive tract of the mammalian fetus (Windle, ’40, Chap. VII).


Bloom, W. 1926. The embryogenesis of human bile capillaries and ducts. Am. J. Anat. 36:451.

Hunter, R. H. 1928. A note on the development of the ascending colon. J. Anat. 62:297.

KeUicott, W. E. 1913. Outlines of Chordate Development. Henry Holt & Co., New York.

Lewis, F. T. 1912. Development of the Pancreas. Vol. II. Human Embryology by Keibel and Mall. J. B. Lippincott Co., Philadelphia.

Lineback, P. E. 1916. The development of the spiral coil in the large intestine of the pig. Am. J. Anat. 20:483.

Platt, J. B. 1891. Further contribution to the morphology of the vertebrate head. Anat, Anz. 6:251.

Thyng, F. W. 1908. Models of the pancreas in embryos of the pig, rabbit, cat and man. Am. J. Anat. 7:489.

Windle, W. F. 1940. Physiology of the Fetus. W. B. Saunders Co., Philadelphia.



Respiratory and Buoyancy Systems

A. Introduction

1. External and internal respiration

2. Basic structural relationships involved in external respiration

a. Cellular relationships

b. Sites or areas where external respiration is accomplished

c. Main types of organs used for respiration

B. Development of bronchial or gill respiratory organs

1. Development of gills in fishes

a. Development of gills in Squalus acant/iias

b. Gills of teleost fishes

c. External gills

2. Development of gills in Amphibia

a. General features

b. Development of gills in Nectunis maculosus

c. Development of gills in the larva of the frog, Rana pipiens

1) Development of external gills

2) Formation of the operculum

3) Internal gills

4) Resorption and obliteration of gills

C. Development of lungs and buoyancy structures

1. General relationship between lungs and air bladders

2. Development of lungs

a. Development of lungs in the frog and other Amphibia

b. Lung development in the chick

1 ) General features of lung development

2) Formation of air sacs

3) Formation of the bronchi and respiratory areas of the chick’s lung

4) Trachea, voice box, and ultimate position of the bird’s lung in the body

5) Basic cellular composition of the trachea, lungs, and air sacs

c. Development of lungs in the mammal

1 ) Origin of the lung rudiment

2) Formation of the bronchi

3) Formation of the respiratory area of the lung

4) Development of the epiglottis and voice box

5) Cellular composition

6) Ultimate position of the mammalian lung in the body

3. Development of air bladders

4. Lunglessness



A. Introduction

1. External and Internal Respiration

Respiration consists of two phases: (1) external and (2) internal. External respiration enables the organism to acquire oxygen from its external environment and to discharge carbon dioxide into this environment. Internal respiration is the utilization of oxygen and the elimination of carbon dioxide by the cells and tissues of the organism. The formation of the structural mechanisms related to external respiration, in many vertebrates, is associated intimately with buoyancy functions. The development of external respiratory and buoyancy mechanisms is discussed in this chapter.

2. Basic Structural Relationships Involved in External Respiration

a. Cellular Relationships

In effecting external respiration, it is necessary for blood capillaries to come into a close relationship with a moist or watery medium containing sufficient amounts of oxygen and a lowered content of carbon dioxide. The mechanisms permitting this relationship vary in different vertebrates. In lower vertebrates, blood capillaries in the gills or in the skin are brought near the watery medium containing oxygen, while, in higher vertebrates, lungs are used for this purpose. In lower vertebrates, an epithelial layer of cells is always interposed between the blood stream and the oxygen-containing fluid. Small amounts of mesenchyme or connective tissue may interpose also (fig. 299B & C). However, in the air capillaries of the lungs of birds (fig. 307C) and in the air cells (alveoli) of mammalian lungs (figs. 299 A; 309G), the surrounding blood capillaries may be exposed intimately to the air-fluid mixture containing oxygen, and the barrier of epithelium between the blood capillaries and the air mixture may be greatly reduced if not entirely absent.

b. Sites or Areas Where External Respiration Is Accomplished

External respiration is achieved in various areas in the embryos and adults of different vertebrate species. In the early shark embryo, external gill filaments, attached to the pharyngeal area, serve as a mechanism for effecting external respiration (fig. 299D), whereas, in the chick and reptile embryo, allantoic contacts with surface membranes of the egg are important (fig. 299E) . In the frog tadpole, the flattened tail region is a factor, as well as the presence of gills and lungs associated with the pharyngeal area. The embryos of higher mammals utilize allantoic-placental relationships for this phase of respiration (see Chap. 22). Similarly, in adult vertebrate species, various areas of the body are used as respiratory mechanisms, such as a moist skin (fig. 299B), gills, lungs, vascular villosities, or papillae (fig. 299F). The skin is most im



portant in the amphibian group as a respiratory mechanism (Noble, ’31, pp. 162, 174-175). However, considering the vertebrate group in its entirety, the branchial or pharyngeal area is the particular part of the developing body devoted to the formation of adult respiratory mechanisms.

c. Main Types of Organs Used for Respiration

Two main types of respiratory organs are developed in the vertebrate group:

( 1 ) branchial organs or gills in water-living forms and

(2) pulmonary organs or lungs in land-frequenting species.

Both of these organs represent pharyngeal modifications.

B. Development of Branchial or Gill Respiratory Organs

As observed in the previous chapter, p. 618, the invaginating branchial grooves and the outpocketing branchial pouches come together in apposition in the early embryos of all vertebrate species, and, in water-living forms, varying numbers of these pouch-groove relationships perforate to form the gill slits. In cyclostomatous fishes (fig. 301 A, B), the number of perforations is six or more pairs; in elasmobranch and teleost fishes, there are five or six pairs (fig. 301C, D); and in amphibia, two or three pairs become perforated. In general, the first pair of branchial-pouch-groove areas is concerned with the formation of the spiracular openings or with the auditory mechanisms. However, in some species it may be vestigial. In water-inhabiting species, the succeeding pairs of pouch-groove areas and their accompanying visceral arches may develop gill structures. (See p. 669, visceral skeleton.)

Two types of gill mechanisms are developed in the vertebrate group:

( 1 ) internal gills in fishes and

(2) external gills in amphibia and in lung fishes.

in all cases, gill development involves a modification of visceral-arch structure. This modification involves the external surface membranes and blood vessels of the arches. The first two pairs of visceral arches, the hyoid and mandibular, are utilized generally throughout the vertebrate series in jaw and tongue formation (sec Chap. 13). On the other hand, the third and succeeding pairs of visceral arches are potentially branchial or gill-bearing arches in

Fio. 299. Structural relationships of respiratory surfaces. (A after Clements, ’38; B after Noble, ’31; H after Patten: Am. Scientist, vol. 39, ’51; F and G after Noble, ’25; C and D original.) (A) Respiratory surface in air sac of pig, 18 hrs. after birth. Capillaries are exposed to air surface. (B) Section through epidermis of respiratory, integumentary folds along the sides of the body of Cryptobranchiis aileganiensis. (C) Transverse section of external gill filament of Rami pipiens. (D) External gill filaments of Squalus acanthias. (E) The allantoic-egg-surface relationship of the developing chick embryo. (F) Respiratory villosities or “hair” of Astylosternus robustus, the hairy frog. (G) vSection through skin of vascular villosity shown in (F).



Fig. 300. Respiratory surface relationships in fishes. (AC original; D and E after Romer: The Vertebrate Body, 1949, Philadelphia, Saunders.) (A-C) External gill filaments and developing gill lamellae on gill arch of shark embryo, Squalus acanthias. (D) Section of gill arch of a shark. (E) Section of gill arch of a teleost fish.

water-living forms. In reptiles, birds, and mammals, the potency for gill formation by these arches ostensibly is lost.

1. Development of Gills in Fishes a. Development of Gills in Squalus acanthias

As the developing gill arch of Squalus acanthias enlarges, the lateral portion extends outward as a flattened membrane, the gill septum (fig. 300A). On the posterior surface of the early gill arch, the covering epithelium produces elongated structures, the external gill filaments. Each gill filament contains a capillary loop which connects with the afferent and efferent branchial arteries (see Chap. 17). These filaments are numerous and give the branchial area a bushy appearance when viewed externally (fig. 300B). The epithelial covering on the anterior face of the gill arch, in the meantime, produces elongated, lamella-like folds, the gill lamellae or gill plates (fig. 300C). During later embryonic life, the external gill filaments are retracted and resorbcd as gill lamellae are developed at the basal area of the filaments. The gill arch thus comes to have a scries of gill lamellae or plates developed on anterior and posterior surfaces, i.e., the surfaces facing the gill-slit passageway. The gill plates on each surface of the gill arch form a demibranch, and the two demibranchs constitute a holobranch or complete gill.

Meanwhile, internal changes occur within the branchial arch. The original aortal (vascular) arch becomes divided into efferent and afferent aortal arteries, with capillaries interposed between the two (fig. 341 A-D). Afferent capillaries bring blood from the afferent portion of the aortal arch to the gill lamellae, while efferent capillaries return the blood to the efferent segment of the aortal arch. Associated with these changes, a skeletal support for the gill arch and gill septum is formed (fig. 315C and D). It is to be observed that the branchial or gill rays extend outward between the lamellae and thus form a series of supports for the gill septum and lamellae. Musculature is developed also in relation to each gill arch (fig. 327B).



h. Gills of Teleost Fishes

Gill development in teleost fishes is similar to that of Squalus acanthias, but the gill septum is reduced, more in some species than in others (fig. 300D, E). An operculum or external covering of the gills, supported by a bony skeleton, also is developed. The operculum forms an armor-like, protective door, hinged anteriorly, which may be opened and closed by opercular muscles (fig. 301D).

c. External Gills

Aside from the formation of external gill filaments as mentioned above (fig. 300B), true external gills, resembling those of Amphibia, occur in most of the dipnoan (lung) fishes and Polypterus in the larval stages (fig. 302A).

2. Development of Gills in Amphibia a. General Features

The gills of Amphibia occur only in the larval condition and in some adults which retain a complete aquatic existence, such as the mud puppy, Necturus maculosus, and the axolotl, Ambystoma rnexicanum. In other adult amphibia which have not renounced a continuous watery existence, such as Amphiuma and Cryptobranchus, the larval gills also are lost. Cryptobranchus relies largely upon the skin as a respiratory mechanism (fig. 299B). External gills are formed in the larval stage of all amphibia, and, in some, they present a bizarre appearance (Noble, ’31, Chaps. Ill and VII). In the frog tadpole, external gills are formed first, to be superseded later by an internal variety.

The amphibian external gill is a pharyngeal respiratory device which differs

Fig. 301. Gill arrangement in various fishes. (After Dean: Fishes, Living and Fossil, 1895, New York and London, Macmillan and Co.) (A) Polistotrema (Bdellostoma). (B) Hagfish, Myxine. (C) Shark. (D) Teleost.



Fig, 302. External gills. (A after Kerr: Chap. 9, Entwicklungsgeschichte tier Wirbeltiere, by Keibel, Jena, G. Fischer; B from Noble, ’31; C-E original.) (A) Larval form of Lepidosiren paradoxa. (B) Larval form of Pseudohranchus striatus. (C, D) Early developmental stages of Necturus maculosus. (E) Gill filaments on gill of adult Necturus.

considerably from that found in most fishes. In many species, the gill is a columnar musculo-connective tissue structure with side branches, projecting outward from a restricted area of the branchial arch (fig. 302B). Gill filaments or cutaneous vascular villosities extend outward from the tree-like branches of the central column. The exact pattern differs with the species. In some amphibian larvae, the gill is a voluminous sac-like affair (sec Noble, ’31, p. 61).

As observed in the previous chapter, there are five pairs of branchial-pouchgroove relationships in frogs and salamanders, although six may occur in the Gymnophiona (Noble, ’31, p. 159). In the Gymnophiona, also, the first pair of branchial pouches perforates to the exterior for a while during embryonic life and each perforation forms a spiracle similar to that of the sharks and certain other fish. Later it degenerates. In other Amphibia, the first pair of branchial pouches never perforates to the exterior. It is concerned with the formation of the Eustachian tubes, as in most frogs and toads, or it degenerates and eventually disappears. The second, third, fourth, and fifth pairs of branchial pouches perforate variously in different Amphibia. In the frog, Rana pipiens, the second, third, and fourth branchial-pouch-groove relationships generally perforate, and sometimes the fifth does also. In Necturus maculosus, the third and fourth pairs normally perforate.



b. Development of Gills in Necturus maculosus

The gills of Necturus arise at about the 10- to 14-mm. stage as fleshy columnar outgrowths from a limited region of the third, fourth, and fifth visceral arches (i.e., the first, second, and third branchial bars or gill arches). (See fig. 302C.) These outgrowths are at first conical in shape (fig. 227) but later become compressed laterally. Epidermal outgrowths or gill filaments arise from the sides of these outgrowing gill columns (fig. 302C, D). (See Eycleshymer, ’06.) As the larva grows and matures, the development of gill filaments from the sides of the gill columns becomes profuse (fig. 302E). During the elaboration of the gill column and gill filaments, the original aortal (vascular) arch becomes separated into two main components, the afferent artery from the ventral aorta to the gill column and an efferent artery from the gill column to the dorsal aorta (Chap. 17).

c. Development of Gills in the iMrva of the Frog, Rana pipiens

1) Development of External Gills. As stated on p. 639, two types of gills are developed in the frog larva, external and internal. The external gills are developed as follows: At about the 5-mm. stage, the gill-plate area on either side of the embryo begins to be divided into ridges by vertical furrows (fig. 303A). Eventually, three ridges appear. These ridges represent the third, fourth, and fifth visceral arches (i.e., the first, second, and third branchial arches). From the upper external edges of these arches, a conical protuberance begins to grow outward, beginning first on the first branchial arch. Ultimately, three pairs of these fleshy columns are formed (fig. 3()3B). From these gill columns, finger-like outgrowths, the gill filaments, arise. An abortive type of gill may form also in relation to the fourth branchial arch. The gill column and the filaments possess the ability to expand and contract.

2) Formation of the Operculum. At approximately the 9- to 10-mm. stage, an oro-pharyngeal opening is formed by rupture of the pharyngeal membrane. At this time, also, the opercular membranes arise. Each operculum arises as a fold of tissue along the caudal edge of the hyoid or second visceral arch. This opercular fold on either side grows backward over the gill area. Eventually, the two opercula fuse ventrally and laterally with the body wall to form a gill chamber for the gills (fig. 303C). On the right side the fusion of the operculum with the body wall is complete. However, on the left side the fusion of the operculum in the mid-lateral area of the body wall is incomplete and a small opening remains as the opercular opening (fig. 257B') 3) Internal Gills. During the above period of opercular development, the external gills become transformed into internal gills, and branchial clefts form between the gill arches. In doing so, the external gill columns gradually shrink, and small, delicate, gill filaments sprout from the outer edges of the gill arches (fig. 303D). External respiration is achieved now not by a movement of the gill in the external medium, as previously, but by the passage of water into



the mouth, through the gill slit, over the gill filament, and, from thence, through the opercular opening to the exterior. Both types of gill filaments, external and internal, fundamentally are similar.

4) Resorption and Obliteration of Gills. The resorption of gills is a phenomenon associated with metamorphosis in dipnoan fishes and in Amphibia, although certain species of Amphibia, as indicated on p. 639, retain certain larval characteristics in the adult condition. Most species metamorphose into an adult form which necessitates many changes in body structure (Noble, ’31, p. 102). This transformation has been related to the thyroid hormone (Chap. 21 ). In frogs, toads, and salamanders, the thyroid hormone produces degeneration and resorption of gills, the branchial clefts fuse, and the larval branchial skeleton is changed into the adult form (fig. 317).

An interesting feature of gill resorption in the anuran tadpole is that the degenerating gills produce a cytolytic substance which brings about the formation of the hole in the operculum through which the foreleg protrudes during metamorphosis (Helff, ’24; Noble, ’31, p. 103).

C. Development of Lungs and Buoyancy Structures

1. General Relationship Between Lungs and Air Bladders

The functions of buoyancy and external respiration are related closely. Lungs and air bladders (sacs) constitute a series of pharyngeal diverticula associated with these functions (fig. 304A-F). (For an historical approach to the work on developing lungs, see Flint, ’06; for studies on air bladders, consult Goodrich, ’30.) Air bladders (sacs) arc a characteristic feature of

Fig. 303. Gill development in the tadpole of Rana pipiens. (All drawings are original.) (A) Five- to six-mm. tadpole. (B) Frontal section of 7-mm. tadpole. (C) External, ventral view of 10-mm. tadpole, showing opercular fold covering gill area. (D) Gill bar, internal and external giil filaments of 10- to 11 -mm. stage.














Fig. 304. Swim-bladder and lung relationships. (A-F slightly modified from Dean: Fishes, Living and Fossil, 1895, New York and London, Macmillan and Co.; G after Goodrich, ’30.) (A E) Sagittal and transverse sections of swim-bladder relationships. (F) Lung relationship of Dipnoi and Tetrapoda. (G) Diagram of physoclistous swim bladder of teleost fish.

most teleost and ganoid fishes. In elasmobranch and cyclostomatous fishes, the air bladder is absent. Two main types of air bladders are found:

( 1 ) a phy.soclistous type (fig. 304G), in which a direct connection with the pharyngeal area is lost (e.g., the toadfish, Opsanus tan), and

(2) a more primitive physostomous variety (fig. 304A-E), retaining a pharyngeal or pneumatic duct (e.g., the common pike or pickerel, Esox Indus).

One function of the air bladder presumably is to alter the density of the fish in such a way as to keep its density as a whole equal to the surrounding water at various levels (Goodrich, ’30, p. 586). Buoyancy, therefore, is one of the main functions of the air bladder.

The air bladders of fishes, in some cases at least, have both respiratory or lung and buoyancy functions (Goodrich, ’30, pp. 578-593). In the bony ganoid fishes, Amia calva and Lepisosteus osseus (fig. 304B), the air bladder apparently has a primary function of external respiration and, therefore, may



be regarded as a lung which secondarily is associated with the function of buoyancy. The latter condition is found also in the Dipnoi (lungfishes) .

The lung of the mud puppy, Necturus maculosus, is capable of considerable extension, particularly in the antero-posterior direction, is devoid of air cells within, and, hence, probably serves the buoyancy function as much or more than that of respiration. The lungs of sea turtles are capable of great distension and aid the animal in maintaining a position near the surface of the water. In the bird group, air sacs are united directly to the lungs, as sac-like extensions of the latter.

Thus, the formation of structures which assume the responsibility for the functions of buoyancy and respiration is a characteristic feature of pharyngeal development in most vertebrate species.

2. Development of Lungs

a. Development of Lungs in the Frog and Other Amphibia

In the 5- to 6-mm. embryo of Rana pipiens, the lungs arise as a solid evagination of the midventral area of the pharynx at the level of the fifth branchial pouches and over the developing heart. At the 7-mm. stage from this evagination, two lung rudiments begin to extend caudally below the developing esophagus (fig. 305). In the 10-mm. embryo, the lungs extend backward from a common tracheal area above the heart and liver area (fig. 258D). At this time, the entodermal lung buds are surrounded by a mass of mesenchyme and coelomic epithelium. The entodermal lining eventually becomes folded to form larger and smaller air chambers.

In Necturus, the development of lungs is similar to that of the frog, but the inner surface of the lungs remains quite smooth. The tracheal area of the frog and Necturus shows little differentiation and represents a comparatively short chamber from the lungs to the glottis. In some urodeles, the trachea is well differentiated, possessing cartilaginous, supporting structures (e.g., Amphiuma, Siren ) .

Fig. 305. Lung rudiment of 7-mm. of frog tadpole. (Cf. fig. 258.)



Fig. 306. Lung development in the chick. (All figures, with the exception of A, were redrawn from Locy and Larsell: ’16, Am. J. Anat., vols. 19, 20; A original.) (A) External view of lung rudiment during third day of incubation. (B) Transverse section through pharynx and lung pouches of embryo of 52 to 53 hrs. of incubation. (C) Section slightly anterior to (B), showing laryngotracheal groove. (D) Lateral view of lung outgrowth of chick at close of fourth day of incubation. (E) Diagram of dissection, exposing left lung of 9-day embryo. Air sacs are now evident; observe relation of heart to lungs. (F) Ventral view of lungs and air sacs of 12-day embryo. (G) Diagram of lateral view of bronchi of 9-day embryo. Four ectobronchi, from which parabronchi are arising, are shown at right of figure.

b. Lung Development in the Chick

1) General Features of Lung Development. The development of lungs in the chick differs greatly from that in the Amphibia and other vertebrates. (For a thorough description of the developing lung of the chick, reference should be made to Locy and Larsell, ’16, a and b.)

Lung development begins during the first part of the third day of incubation in the form oFventro-lateraT, ridp^-like enlargements of the pharynx, immediately posterior to the fourth pair of branchial (visceral) pouches. These evaginations arise from a ventral, groove-like trough of the pharyngeal floor (fig. 306A). The entire area of the pliaryngeal floor, where the lung rudiments begin to develop, gradually sinks below the pharyngeal-esophageal level, and its remaining connection with the pharynx proper is the laryngotracheal groove in the floor of the pharynx (fig. 306B, C).

After the lung and tracheal rudiments arc formed, they extend backward



rapidly into the surrounding mesenchyme and they soon project dorsaJ]yj._as indicated in figure 306D. The latter figure presents the developmental condition of the lung rudiments late on the fourth day of incubation. Two areas of the lung rudiment are evident, namely, the tracheal and lung rudiments proper. The external appearance of the developing lungs on the ninth day of incubation is shown in figure 306E, while that of the twelfth day with the forming air sacs is shown in figure 306F.

2) Formation of Air Sacs. The air sacs arise as extensions from the main bronchi during the sixth to seventh day of incubation. During the ninth day,^ they are present as well-developed structures (fig. 306E). The abdominal air sac appears as a posterior continuation of the mesobronchus or primary bronchus of the lung, while the cervical air sac arises from the anterior ento

Fio. 307. Lung development in the chick. (All figures, after Locy and Larsell: ’16, Am. J. Anat., vols. 19, 20.) (A) Diagram of dissection of lung of 9y2-day embryo,

designed to show entobronchi and air-sac connections with bronchial tree. (B) Diagram of mesial aspect of adult lung, showing parabronchial connections between entobronchi and ectobronchi. Dorsal and lateral bronchi are not shown. (C) Simplified diagram to show air capillaries in relation to infundibula and parabronchus. (Blood capillaries added to one sector of figure represent a modification of the original figure.) (D) Diagram of lateral surface of right lung of 15-day embryo, showing recurrent bronchi of abdominal and posterior intermediate air sacs. Anastomoses of recurrent bronchi are also shown.



Fig. 308. Respiratory structures in adult birds. (A after Kingsley, ’12, Comparative Anatomy of Vertebrates, Philadelphia, P. Blakiston’s Son & Co.; B slightly modified from Goodrich, ’30.) (A) Syrinx or voice box of canvasback, Aythya. (B) Diagram of

left side view of lungs and air sacs of an adult bird.

bronchus, an outgrowth of the niesobronchus at the anterior extremity of the lung. The anterior intermediate, posterior intermediate, and the interclavicular

air sacs take their origins from the ventral surface of the lungs and represent outgrowths from the entobronchi (figs. 306G, 307A). The interclavicular air sac arises from the fusion of four moieties, two from each lung. The air sacs lie among the viscera and send out slender diverticula, some of which may enter certain bones (fig. 308B).

3) Formation of the Bronchi and Respiratory Areas of the Chick’s Lung.

Internally, the primary bronchial division of each lung passes into the lung’s substance where it continues as the niesobronchus. The mesobronchus thus represents a continuation of the main or primary bronchial stem of the lung and is a part of the original entodermal outpushing from the pharynx. From the niesobronchus, the ectobronchi and entobronchi arise as diverticula (fig. 307A, B ). The parabronchi or lung pipes develop as connections between the ectobronchi and entobronchi (fig. 307B). The parabronchi constitute the respiratory areas of the lung, for the parabronchi send off from their walls elongated diverticula, the infundibula or vestibules. The vestibules are branched distally (fig. 307C) and anastomose with each other to form the air capillaries. The blood capillaries (fig. 307C) ramify profusely between the air capillaries. It is not clear that the air capillaries possess definite cellular walls throughout.

As indicated in figure 307D, other or recurrent bronchi are formed as air passages which arise from the air sacs and grow back into the lungs, where they establish secondary connections with the other bronchi. The air sacs thus represent expanded parts of the bronchial circuits of the lungs which not only




Fig. 309. Lung development in the mammal. (A-F modified from Flint, ’06; G modified from Maximow and Bloom, ’42, A Textbook of Histology, Philadelphia, Saunders.) (A-F) Development of the bronchial tree in the pig. (G) Terminal respiratory relationships in the human lung. Respiratory bronchioles arise from terminal divisions of the terminal bronchiole; from the respiratory bronchiole arise the alveolar ducts which may terminate in spaces, the atria; from the atrium the alveolar sacs arise; and the side walls of each alveolar sac contain the terminal air sacs or alveoli.

provide buoyancy but effect a more thorough utilization of the available air by the respiratory areas of the lungs. That is, all the air passing through the respiratory parts of the lung is active, moving air. (See Locy and Larsell, 16b, pp. 42-43; Goodrich, ’30, pp. 600-607.)

4) Trachea, Voice Box, and Ultimate Position of the Bird’s Lung in the Body. The trachea of the bird’s lung is an elongated structure, reinforced by cartilage rings or plates in the tracheal wall. The voice box of the bird is developed at the base of the trachea in the area of the tracheal division into the



two major bronchi. It is an elaborate structure, consisting of a number of folds of the mucous membrane together with an enlargement of this particular area. This structure is known as the syrinx (fig. 308A). The morphological structure of the syrinx varies from species to species. The ultimate position of the bird’s lung in the body is shown in figure 308B.

5) Basic Cellular Composition of the Trachea, Lungs, and Air Sacs. It is obvious from the description above that the entire lining tissue and the respiratory membrane of the bird’s respiratory and air-sac system are derived from the original entodermal evagination, whereas the muscle, connective, and other tissues are formed from the surrounding mesenchyme.

c. Development of Lungs in the Mammal

1) Origin of the Lung Rudiment. The first indication of the appearance of the lungs in the pig and human embryo is the formation of a midventral trough or furrow in the entoderm of the pharynx, the laryngotracheal groove. This groove forms immediately posterior to the fourth branchial (visceral) pouch, approximately at the stage of 3 to 4 mm. in both pig and human. In the human, about the fourth week, and 3-mm. pig, the laryngotracheal groove deepens, and its posterior end gradually forms a blind, finger-like pouch which creeps posteriorly below the esophageal area as a separate structure (fig. 309A). Thus, the original laryngotracheal groove is restricted to the cephalic end of the developing lung rudiment, where it forms a slit-like orifice in the midventral floor of the pharynx at about the level of the fifth visceral (i.e., third branchial) arch.

2) Formation of the Bronchi. As the caudal end of the original lung rudiment grows caudad, it soon bifurcates into left and right bronchial stems as shown in figure 309B. Each primary or stem bronchus is slightly enlarged at the distal end. As the stem bronchi of the right and left lung buds continue to grow distally, evaginations or secondary bronchi arise progressively from the primary bronchi as indicated in figure 309C-E. While this statement holds true for the human embryo, the apical bronchus (i.e., eparterial bronchus because this lobe of the lung comes to lie anterior to the pulmonary artery) in the pig arises directly from the trachea as shown in figure 309D. Each of these secondary bronchi forms the main bronchus for the upper and middle lobes of the lungs (fig. 309D, E). From each lobular bronchus, other bronchial buds arise progressively and dichotomously, with the result that the bronchial system within each lobe of the lung becomes complex, simulating the branches upon the limb of a tree. Considerable variation may exist in the formation of the various bronchi in different individuals.

3) Formation of the Respiratory Area of the Lung. This growth of bronchial buds of the pulmonary tree continues during fetal life and for a considerable time after birth. The large bronchi give rise to smaller bronchi, and, from the latter, bronchioles of several orders originate. Finally, the terminal bronchioles



arise. Fifty to eighty terminal bronchioles have been estimated to be present for each lobule of the human lung (Maximow and Bloom, ’42, p. 465). From each of the terminal bronchioles, a varying number of respiratory bronchioles arise, which in turn give origin to the alveolar ducts, and, from the latter, arise the alveolar sacs and alveoli. Each alveolus represents a thin-walled compartment of the alveolar sac (fig. 309G). The exact cellular structure of the terminal air compartments or alveoli is not clear. In the frog lung, a layer of flattened epithelium is present. However, in the lung of the bird and the mammal, this epithelial lining may not be complete, and the wall of the alveolus may be formed, in part at least, by the endothelial cells of the surrounding capillaries (fig. 299A; Palmer, ’36; Clements, ’38).

4) Development of the Epiglottis and Voice Box. The epiglottis is the structure which folds over the glottis and thus covers it during deglutition. The glottis is the opening of the trachea into the pharynx. An epiglottis is found only in mammals. It arises as a fold in the pharyngeal floor in the area between the third and fourth visceral arches. It grows upward and backward in front of the developing glottis (fig. 310A~C) . In the meantime, the arytenoid swellings or ridges appear on either side of the glottis.

The larynx or voice box is an oval-shaped compartment at the anterior end of the trachea in mammals. It is supported by cartilages derived from the visceral arches (Chap. 15). The vocal cords arise as transverse folds along the lateral sides of the laryngeal wall.

5) Cellular Composition. The epithelial lining of the larynx, trachea, bronchi, etc., is derived from the entodermal outpushing, whereas the sur



Fig. 310. Development of the epiglottis and entrance into the larynx in the human embryo. (Consult also fig. 285.) (All figures slightly modified from Keibel and Mall: Manual of Human Embryology, vol. II, ’12, Philadelphia, Lippincott.) (A) About 16-mm., crown-rump length, 7 to 8 weeks. (B) About 40-mm., crown-rump length, 9 to 10 weeks. (C) Late fetal condition.



rounding mesenchyme gives origin to the cartilage, muscle, and connective tissue present in these structures.

6) Ultimate Position of the Mammalian Lung in the Body. See Chapter 20.

3. Development of Air Bladders

It is difficult to draw a clear distinction between air bladders of Pisces and the lungs of Tetrapoda. Air bladders and gills appear to be the standard arrangement for most fishes. It is probable, therefore, that the function of external respiration rests mainly upon the branchiae or gills in all fishes other than the Dipnoi, while the function of buoyancy is the responsibility of the air bladder. In some fishes (Dipnoi and ganoids), the functions of buoyancy and respiration converge into one structure, the air bladder or lung, as they do in many Tetrapoda.

In development, air bladders, like the lungs of all Tetrapoda, arise as diverticula of the posterior pharyngeal area. In most cases, the air bladder arises as a dorsal diverticulum (fig. 304A, B), while, in other instances, its origin appears to be from the lateral wall (fig, 304C). In Salmonidae, Siluridae, etc., for example, it arises from the right wall, while in Cyprinidae, Characinidae, etc., it takes its origin from the left wall. The air bladder generally is a single structure (fig. 304A, C, D), but in some cases it is double or bilobed (fig. 304E).

Generally speaking, the air bladder receives blood from the dorsal aorta or its immediate branches (fig. 304G), but in Dipnoi and Polypterus, the blood supply to the air bladder comes from the pulmonary arteries as it does in Tetrapoda.

4. Lunglessness

Many urodele amphibia have reduced or lost their lungs entirely. In many cases the reduced condition of the lungs or absence of lungs is compensated for by the development of buccopharyngeal respiration. The latter type of respiration depends upon an extreme vascularization of the pharyngeal and caudal mouth epithelium and rapid throat movements which suck the air in and then expel it. In Aneides (Autodax) liigubrus, a land form, these throat movements may reach 120 to 180 movements per minute (Ritter and Miller, 1899). Lungless aquatic salamanders also practice buccopharyngeal respiration, although, in Pseudotriton ruber, cutaneous respiration evidently is resorted to (Noble, ’25).


Clements, L. P. 1938. Embryonic develop- Eycleshymer, A. C. 1906. The growth and ment of the respiratory portion of the regeneration of the gills in the young pig’s lung. Anat. Rec. 70:575. ‘ Necturus. Biol. Bull. X: 171.



Flint, J. M. 1906. The development of the lungs. Am. J. Anat. 6:1.

Goodrich, E. S. 1930. Studies on the Structure and Development of Vertebrates. Macmillan and Co., London.

HelflF, O. M. 1924. Factors involved in the formation of the opercular leg perforation in anuran larvae during metamorphosis. Anat. Rec. 29:102.

Locy, W. A. and Larscll, O. 1916a. The embryology of the bird’s lung. Based on observations of the domestic fowl. Part 1. Am. J. Anat. 19:447.

and . 1916b. The embryology of the bird’s lung. Based on observations of the domestic fowl. Part II. Am. J. Anat. 20: 1.

Maximow, A. A. and Bloom, W. 1942. A Textbook of Histology. W. B. Saunders Co., Philadelphia.

Noble, G. K. 1925. The integumentary, pulmonary and cardiac modifications correlated with increased cutaneous respiration in the Amphibia; a solution to the “hairy frog’’ problem. J. Morphol. & Physiol. 40:341.

. 1931. The Biology of the Amphibia. McGraw-Hill Book Co., Inc., New York.

Palmer, D. W. 1936. The lung of a human foetus of 170 mm. C. R. length. Am. J. Anat. 58:59.

Ritter, W. E. and Miller, L. 1899. A contribution to the life history of Autodax lupubris Hallow., a Californian salamander. Am. Nat. 33:691.


Tke Skeletal System

A. Introduction

1. Definition

2. Generalized or basic embryonic skeleton; its origin and significance

a. Basic condition of the skeletal system

b. Origin of the primitive ghost skeleton

1) Notochord and subnotochordal rod

2) Origin of the mesenchyme of the early embryonic skeleton

c. Importance of the mesenchymal packing tissue of the early embryo

B. Characteristics and kinds of connective tissues

1. Connective tissue proper

a. Fibrous types

1) Reticular tissue

2) White fibrous tissue

3) Elastic tissue

b. Adipose tissue

2. Cartilage

a. Hyaline cartilage

b. Fibrocartilage

c. Elastic cartilage

3. Bone

a. Characteristics of bone

b. Types of bone

c. Characteristics of spongy bone

d. Compact bone

C. Development of skeletal tissues

1. Formation of the connective tissue proper

a. Formation of fibrous connective tissues

b. Formation of adipose or fatty connective tissue

2. Development of cartilage

3. Development of bone

a. Membranous bone formation

b. Endochondral and perichondrial (periosteal) bone formation

1) Endochrondral bone formation

2) Perichondrial (periosteal) bone formation

c. Conversion of cancellous bone into compact bone

D. Development (morphogenesis) of the endoskeleton 1. Definitions




2. Morphogenesis of the axial skeleton

a. General features of the skeleton of the head

1 ) Neurocranium or cranium proper

2) Visceral skeleton or splanchnocranium

3) Development of the skull or neurocranium

4) Vicissitudes of the splanchnocranium

b. Ossification centers and the development of bony skulls

c. Development of the axial skeleton

1) Axial skeleton of the trunk

a) Notochord

b) Vertebrae

c) Divisions of the vertebral column

d) Ribs

e) Sternum

2) Axial skeleton of the tail

d. Development of the appendicular skeleton of the paired appendages

1) General features

2) Development of the skeleton of the free appendage

3) Formation of the girdles

e. Growth of bone

f. Formation of joints

1) Definitions

2) Ankylosis (synosteosis) and synarthrosis

3) Diarthroses

4) Amphiarthroses

g. Dermal bones

A. Introduction

1. Definition

The word skeleton is used commonly to denote the hard, supporting framework of the body, composed of bone and cartilage. In this restricted sense it is employed to refer particularly to the internal or endoskeleton (see p. 668). The word has a broader meaning, however, for the skeletal system includes not only the bony and cartilaginous materials of the deeper-lying, internal skeleton but also the softer, pliable connective tissues as well. Thus, the skeletal tissues in a comprehensive sense may be divided as follows:

(1) the soft skeleton, composed of pliable connective tissues which bind together and support the various organs of the body and

(2) the hard or firm skeleton, formed of bone, cartilage, and other structures which protect and sustain, and give rigidity to the body as a whole. The exoskeletal structures described in Chapter 12 in reality are a part of the hard, protective skeleton of the vertebrate body.

{Note: Blood and lymph are often classified as a part of the connective tissues. See Maximow and Bloom, ’42, p, 39.)







sclerotomic mesenchyme




y irfiy .l — 1 V u A y endothelium

-dermatomic mesenchyme gives origin to derma.

. dermal bone and

dermal scales

> mesenchyme gives â– origin to hemal rii


mesenchyme FORMS' smooth muscle A l SO CARDIAC STRIATED MUSCLE

â– ventral dermal mesench'



>LEURAL (hemal)




Fig. 311. (A) Diagram showing basic mesenchymal packing tissue around the various body tubes and notochord. (B) Contribution of embryonic mesenchyme to adult skeletal tissue.

2. Generalized or Basic Embryonic Skeleton;

Its Origin and Significance

a. Basic Condition of the Skeletal System

The generalized or basic skeleton of the embryo which has achieved primitive body form is composed of the notochord or primitive skeletal axis, together with the mass of mesenchyme which comes to fill the spaces between the epidermal, neural, enteric, mesodermal, and primitive circulatory tubes. Because of the delicate nature of the mesenchymal cells and the coagulable intercellular substance between them, this primitive skeleton sometimes is referred to as the “ghost skeleton” (fig. 31 1 A).

b. Origin of the Primitive Ghost Skeleton

1) Notochord and Subnotochordal Rod. As observed in Chapters 9 and 10, the notochord becomes segregated as a distinct entity during gastrulation and embryonic body formation. It soon comes to form a rod-like structure, surrounded by a primitive notochordal membrane. The notochordal axis extends from the pituitary body (hypophysis) and diencephalic region of the brain caudally to the end of the tail (fig. 217). In many of the lower vertebrates, a second rod of cells, the hypochord or subnotochordal rod, evaginates and segregates from the roof of the gut in the trunk region of the embryo during tubulation and early body-form development; it comes to lie immediately below the notochord (fig. 228). The subnotochoral rod soon degenerates.



The notochord never extends cranialward beyond the hypophysis and infundibular downpushing from the diencephalon in any of the vertebrates. This meeting place of the hypophysis, notochord, and infundibulum is a constant feature of early vertebrate structure from the cyclostomatous fishes to the mammals. In Amphioxus, however, the notochord projects anteriad beyond the limits of the “brain” (fig. 249D, E).

2) Origin of the Mesenchyme of the Early Embryonic Skeleton, The origin of mesenchyme in the early embryo is set forth in Chapter 1 1 , page 520.

c. Importance of the Mesenchymal Packing Tissue of the Early Embryo

The mass of mesenchymal cells which comes to lie between the embryonic body tubes not only forms the primitive skeletal material of the early embryo but it also serves as a reservoir from which later arise many types of cells and tissues, as indicated in the following diagram:

endothelial cells of capillaries and other blood vessels "^lipoblasts â–ºfat cells

^^chondroblasts (cartilage-forming cells) â–ºchondrocytes

and cartilage

✓fibroblasts ►fibrous connective tissue

^osteoblasts â–ºosteocytes and bony substances, including

Mesenchymal dermal bones and the dermal substances of scales

cells macrophages â–ºphagocytes

^hemocytoblast (free, wandering, mesenchymal cell) erythrocytes Vyrnonocytes

Vblood platelets 'white blood cells 'myoblasts (for smooth, cardiac.

and skeletal muscle)

In regard to the skeletal system, it is pertinent to point out the fact that wherever mesenchyme exists, the possibility for connective tissue development also exists,

B. Characteristics and Kinds of Connective Tissues

Connective tissues, other than adipose tissue, are characterized by the presence of intercellular substances which become greater in quantity than the cellular units themselves. In consequence, the various types of connective tissue are classified in terms of the intercellular substance present. Excluding the blood, three main categories of connective tissues are found:

( 1 ) connective tissue proper,

(2) cartilage, and

( 3 ) bone.



1. Connective Tissue Proper

The connective tissues proper may be divided into

(a) fibrous types and

(b) fatty or adipose tissue.

a. Fibrous Types

1) Reticular Tissue. This type of connective tissue possesses stellate cells, between which are found delicate aggregations of fibrils and a fluid-like, intercellular substance (fig. 3126).

2) White Fibrous Tissue. White fibrous tissue contains bundles or sheets of white, connective-tissue fibers (i.e., collagenous fibers), placed between the cells. Some clastic fibers may be present (fig. 312C, D). Collagenous fibers yield gelatin upon boiling with water and are not digested readily by trypsin (Maximow and Bloom, ’42).

3) Elastic Tissue. Elastic connective tissue is similar to the white fibrous variety but contains a large percentage of elastic tissue fibers which extend under stress but contract again when tension is released (fig. 312E). Elastic fibers are resistant to boiling water and are digested readily by trypsin (Maximow and Bloom, ’42). Elastic tissue may have a yellowish tinge when viewed macroscopically.



u_^E u s'^Q^ ^^O rg '^'ll





Fig. 312. Types of soft connective tissues. (A, D, and E redrawn from Bremer, 1936, Textbook of Histology, Philadelphia, Blakiston; B and C redrawn from Keibel and Mall, 1910, Manual of Human Embryology, vol. I, Philadelphia. Lippincott; F redrawn from Bell, ’09.)





Fig. 313. Types of cartilaginous tissue. (A-C) Development of hyaline cartilage. (D) Destruction of cartilage by perichondrial vascular bud preparatory to ossification. The cartilage spicules may be infiltrated with calcium salt at this period. (Redrawn from Bremer, 1936, Textbook of Histology, Philadelphia, Blakiston.) (E) Fibrocartilage, from area of tendinous union with bone. (F) Elastic cartilage from human, larynx. (Redrawn and modified from Bremer, 1936, Textbook of Histology, Philadelphia, Blakiston.)

b. Adipose Tissue

Adipose tissue contains a fibrous network of white and elastic fibers, between which fat cells develop. Eventually, the fibrous connective tissue is displaced and pushed aside by the fat-containing elements (fig. 312F).

2. Cartilage

Cartilage is a type of connective tissue with a solid intercellular substance. The latter is composed of a fibrous framework filled with an amorphous ground substance. Unlike bone, the intercellular substance may be readily cut with a sharp instrument. Three main types of cartilage are found:

( 1 ) hyaline,

(2) fibrous, and

(3) elastic.

a. Hyaline Cartilage

Hyaline cartilage (fig. 313A-C) is the most widespread variety of cartilage. It is characterized by a solid, amorphous, ground substance, slightly bluish in appearance, easily bent and capable of being cut with a sharp instrument.



The amorphous ground substance or chondrin is reinforced by fibers of the collagenous (white) variety, but the quantity of fiber present is much less than in fibrous or elastic cartilage. The chondrocytes (i.e., the cartilage cells) lie within capsules. Canaliculi apparently do not connect one capsule with another. This type of cartilage forms a considerable part of the temporary axial and appendicular skeleton of the developing organism and remains as the adult axial and appendicular skeleton in cyclostomatous and elasmobranch fishes. In the adults of other vertebrates, it is supplemented to various degrees by bone.

b. Fibrocartilage

Fibrocartilage (fig. 313E) is a transitional form between white fibrous connective tissue and cartilage. It contains bundles of collagenous fibers, placed parallel to each other. Between the fibrous bundles, cartilage capsules are present, containing cartilage cells (chondrocytes). A small amount of amorphous ground substance or chondrin is present, particularly around the cell capsules. Some types of fibrocartilage contain more of the amorphous ground substance than other types. Fibrocartilage is found in the intervertebral discs between the vertebrae, in the area between the two pubic bones in mammals, and in certain ligaments, such as the ligamenlum teres femoris.

c. Elastic Cartilage

Elastic cartilage (fig. 313F) differs from the hyaline variety by the presence of an interstitial substance which contains branching and interlacing fibers of the elastic variety. The elastic fibers penetrate through the amorphous substance in all directions. While hyaline cartilage is bluish in color, the color of elastic cartilage is yellowish. It is found in the external ear of mammals, in the mammalian epiglottis, Eustachian tubes, the tubes of the external auditory meatus, etc.

3. Bone

a. Characteristics of Bone

Bone forms the greater part of the adult skeleton of all vertebrates above the cyclostomatous and elasmobranch fishes. In teleost fishes and in landfrequenting vertebrates, it tends to displace most of the cartilaginous substance of the skeleton. The interstitial substance of bone is composed of a fundamental fibrous material similar to that of connective tissue. These fibers are called osteocollagenous fibers. A small amount of amorphous ground substance also is present. The interstices of this fibrous and amorphous substrate are infiltrated with mineral salts, particularly calcium salts, to form the bony substance. The latter is formed in layers, each layer constituting a lamella. The bone cells or osteocytes are present in small cavities or lacunae between the lamellae. The lacunae are connected with each other by small

Fig. 314. Types and development of bone. (A) Compact and cancellous (spongy) bone. (B) Diagram showing structure of compact bone. (Redrawn and slightly modified from Maximow and Bloom, 1942, A Textbook of Histology, Philadelphia, Saunders.) (C) Stages in conversion of marrow canal or space of* spongy bone into an Haversian system by deposition of concentric layers of bony lamellae. (D) Haversian systems of compact bone from thin, ground section. (Redrawn and modified from Bremer, 1936, Textbook of Histology, Philadelphia, Blakiston.)


—hyaline cariilage




SPONGY BONE bony cylinder




marrow substance

Pio. 3l4~(Co/ifi/i/n'i/) Types and development of bone. (H) Diagram showing invasion of eartilage by perichondrial vascular buds, preparatory to deposition of bony substance on cartilaginous spicules produced by erosion of cartilage (compare with fig. 313, D). (F) The formation of spongy bone within, by deposition of bony substance on

cartilaginous spicules. See spicule “A.” Compact bone is deposited on outer surface of cartilaginous replica of future bone by periosteal osteoblasts, forming bony cylinder of compact bone. (Redrawn and modified from Bremer, 1936, Textbook of Histology, Philadelphia, Blakiston.) (G) Formation of membrane bone from jaw of pig embryo. (Redrawn and modified from Bremer, 1936, Textbook of Histology, Philadelphia, Blakiston.) (H ) Bone destruction and resorption. Observe osseous globules within substance of osteoclast. (From Jordan, ’21, Anat. Rec., 20.)




channels or canaliculi which course through the lamellae. Some of the canaliculi join larger channels within the bony substance which contain blood vessels. Bony substance in the living animal, therefore, is living tissue, constructed of the following features (fig. 314):

( 1 ) Bony layers or lamellae are present, composed of a ground substance of fibrous and amorphous materials infiltrated with mineral salts, particularly the salts of calcium (fig. 314A, B);

(2) between the bony layers are small cavities or lacunae, each containing a bone cell or osteocyte (fig. 314B);

(3) coursing through the lamellae and connecting the various lacunae, are small channels, known as canaliculi, into which extend processes from the osteocytes (fig. 314B); and

(4) the canaliculi make contact in certain areas with blood vessels which lie within small canals coursing through the bony substance or in larger spaces, called marrow cavities (fig. 314A, B).

b. Types of Bone

From these fundamental structural features, two types of bone are formed:

( 1 ) spongy and

(2) compact.

The difference between these two types of bone rests upon the proportion of bony substance to blood-vessel area or marrow cavity present, and is not due to a difference in the character of the bony substance itself.

c. Characteristics of Spongy Bone

Spongy bone differs from compact bone in that large marrow cavities or spaces are present between an irregular framework of compact bone. The bony substance present is in the form of a meshwork of irregular columns or trabeculae between the marrow-filled spaces (fig. 314A).

d. Compact Bone

Compact bone (fig. 314A, B, D) lacks the widespread, marrow-filled cavities of the spongy variety, the marrow spaces being reduced to a minimum. This is accomplished by the utilization of a structural unit known as the Haversian system, named after Clopton Havers, an English anatomist who discovered the system during the latter part of the seventeenth century while investigating the blood supply of bone. The bony walls of the shafts of long bones are composed largely of many Haversian systems, associated side by side as shown in figure 314D. Irregular layers (lamellae) lie between the various systems.

The Haversian system is composed of a very narrow canal or lumen, the Haversian canal, around which are placed concentrically arranged bony plates



(lamellae) with their associated lacunae, osteocytcs, and canaliculi (fig. 314B-D). Blood vessels from the marrow cavity within the bone or from the surface of the bone via Volkmann’s canals (fig. 314D) pass into the Haversian canals, thus supplying nourishment and other life-maintaining features to the canaliculi and through the latter to the osteocytes. Compact bone thus restricts the marrow cavity to a central area, and the Haversian and Volkmann canals convey the blood supply into the compact bony substance which surrounds the central marrow cavity. In general, the Haversian systems are formed parallel with the long axis of the bone. Circumferential lamellae surround the external surface of the bone around the Haversian systems. Inner circumferential lamellae also are present lining the marrow cavities of long bones.

C. Development of Skeletal Tissues

1. Formation of the Connective Tissue Proper a. Formation of Fibrous Connective Tissues

In the early embryo, following the ghost-skeleton stage, two types of connective tissues are found:

(1) Mucoid or loose connective tissue is located in Wharton’s jelly in the umbilical cord of mammals and in other parts of the embryo. This embryonic type of connective tissue is characterized by the presence of large mesenchymal cells whose processes contact the processes of other surrounding mesenchymal cells (fig. 312A). Within the meshwork formed by these cells and their processes, mucus or a jelly-like substance is present. Very delicate fibrils may lie within this jelly.

(2) A second type of early embryonic connective tissue is reticular tissue. It contains stellate mesenchymal cells whose processes contact each other (fig. 312B). Very delicate bundles of fibrils may be present which are closely associated with the cells.

The foregoing, connective-tissue conditions of the early embryo eventually are replaced by the mature forms of connective tissue. In this process the reticular type of connective tissue appears to form an initial or primary stage of connective-tissue development. For example, in the development of white fibrous tissue, a delicate network of fine fibrils appears within the ectoplasmic ground substance between the primitive mesenchymal cells, thus forming a kind of reticular tissue (fig. 312A, B). With the appearance of fibrils between the mesenchymal cells, the latter may be regarded as fibroblasts. Following this reticular stage, the ectoplasmic ground substance becomes more fibrillated and parallel bundles of white fibers arise, probably by the direct chemical transformation of the earlier fibrils into white or collagenous fibers (fig. 312C). (See Bardeen, ’10, p. 300.) It is probable that the elastic con



nective tissue with its elastic fibers arise in a similar manner, with the exception that elastic fibers are formed instead of collagenous fibers.

The matter of fiber formation within connective tissues has been the subject of much controversy. The older view of Flemming (Mall, ’02, p. 329) maintains that the fibers arise within the peripheral area of the cytoplasm of the cell from whence they are thrown off into the intercellular space where they continue to grow. However, most observers now agree that the fibrils arise from an intercellular substance, i.e., from the substance lying between the fibroblasts, but the manner by which this intercellular substance itself arises is questionable. Some observers, such as Mall (’02) and Jordan (’39), set forth the interpretation that the intercellular substance is derived from a syncytial ectoplasm which becomes separated from the early mesenchymal cells. Baitsell (’21) and Maximow (’29), however, consider the intercellular substance to be a secretion product of the mesenchymal cells which have become fibroblasts. The observations of Stearns (’40) on living material in a transparent chamber of the rabbit’s ear suggest that the ground substance is exuded by the surface of the fibroblasts and that the fibers then develop within this exudate.

b. Formation of Adipose or Fatty Connective Tissue

Adipose tissue is fibrous connective tissue which contains certain specialized cells of mesenchymal origin, the lipoblasts. The latter have the ability to produce lipoidal substances and to store these substances within the confines of their own boundaries. Adipose or fatty tissue arises in fibrous connective tissues in various parts of the body in proximity to blood capillaries.

Lipogenesis or the formation of the fatty substance is an unsolved problem. Two main types of fat are formed, white and brown. The process of lipogenesis in white fat, according to Schreiner (’15) who studied the process in detail in the hagfish embryo, Myxine glutinosa, consists at first in liberation of small buds from the nucleolus within the nucleus. These buds pass through the nuclear membrane into the cytoplasm as granules or chromidia. In the cytoplasm these granules appear as mitochondria. The latter increase in number by division. The secondary granules then separate and each gives origin to a liposome which liquefies and expands into a small fat globule. Regardless of the exact method by which the small fat globules arise, when once formed, the small globules coalesce to form the large fat globule, typical of white fat, which ultimately pushes the nucleus and cytoplasm of the lipoblast to the periphery (fig. 312F). (Sec Bell, ’09.) Lipoblasts in the mature condition are fat cells or lipocytes.

The above type of fat-cell formation occurs in the subcutaneous areas of the embryo. In the human embryo it begins at about the fourth month. However, aside from the common type or white-fat formation, another kind of fat-cell development occurs in certain restricted areas of the body in the so



called brown fat tissue found in certain adipose glands. It is referred to as brown fat because a brownish pigment may be present in certain mammals. During brown-fat formation, mesenchymal cells become ovoid in shape and develop a highly granular cytoplasm. These granules give origin to small fat globules which remain distinct for a time and do not readily fuse to form the large fat globule, characteristic of white fat. However, they ultimately may coalesce and become indistinguishable from the ordinary lipocyte found in white fat. In man, this type of fat disappears shortly after birth; in the cat, it is present until maturity when it transforms into the ordinary type or white fat; and in the rat, it persists throughout life (Sheldon, ’24). In the woodchuck, this type of fat forms the hibernating gland (Rasmussen, ’23). In mice and other rodents, the presence of a small amount of brownish pigment is evident in this type of fat. In the young monkey, hibernating-gland tissue is found in the cervical, axillary, and thoracic areas (Sheldon, ’24).

2. Development of Cartilage

The formation of cartilage is an interesting process. During the initial stage of cartilage development, mesenchymal cells withdraw their processes, assume a rounded appearance, and become closely aggregated. This condition is known as the pre-cartilage stage (fig. 313A). Gradually the pre-cartilage condition becomes transformed into cartilage by the appearance of the intercellular substance, characteristic of cartilage between the cells (fig. 313B, C). As in the case of the connective tissues described on page 664, two schools of thought explain the appearance of this intercellular substance:

(a) as a modification of the ectoplasm which separates from the chondroblasts and

(b) as a secretion of these cells.

In hyaline cartilage, the homogeneous, amorphous, ground substance is predominant, together with a small number of fibrils; in bbrocartilage, a large number of white, connective-tissue fibers and a smaller amount of the amorphous substance is deposited; and in elastic cartilage, elastic, connectivetissue fibers are formed in considerable numbers. The mesenchyme, immediately surrounding the mass of cartilage, forms the specialized tissue, known as the perichondrium. The perichondrial layer, as the name implies, is the tissue immediately surrounding the cartilage. It connects the cartilage with the surrounding connective tissue and mesenchyme. The inner cells of the perichondrium transform into chondroblasts and deposit cartilage; in this manner the cartilage mass increases in size by addition from without. The latter form of growth is known as peripheral growth. On the other hand, an increase within the mass of cartilage already formed is the result of interstitial growth. Interstitial growth is effected by an increase in the number of cells within the cartilage and by a deposition of intercellular substance between



the cells. The increase in the intercellular substance separates the chondroblasts from each other, and the mass of cartilage expands as a whole. These two types of growth are important processes involved in the increase in size of many body structures. Cartilage formation in the human embryo begins during the fifth and sixth weeks.

3. Development of Bone

Bone develops as the result of the calcification of previously established fibrous or cartilaginous connective tissues. The transformation of fibrous connective tissue into bone is called membranous or intramembranous bone formation, and the process which transforms cartilage into bone constitutes endochondral or intracartilaginous bone development. Membranous bone formation occurs in the superficial areas of the body, particularly in or near the dermal area of the skin whereas cartilaginous bone formation is found more deeply within the substance of the body and its appendages.

a. Membranous Bone Formation

Membranous bone formation occurs as follows (fig. 314G): Thin spicules or bars of a compact intercellular substance, known as ossein, gradually come to surround collagenous (osteogenic) fibers which lie between fibroblast cells. Later, these spicules of ossein become calcified by the action of specialized cells, called osteoblasts, which surround the osseinated fibrils. Osteoblasts may represent transformed fibroblasts or, more directly, transformed mesenchymal cells. With the deposition of the bone salts, the tissue is converted from ossein into bone. Thus, spicules of ossein and connective tissue fibers serve as the basis for bone deposition and become converted into bony spicules. These spicules are converted next into bony columns (trabeculae) by the formation of layers (lamellae) of compact bone around the original bony spicule. Such bony columns or trabeculae are characteristic of spongy bone (fig. 314A). Some of the bone-forming cells become enclosed within the lacunar spaces in the bone during the above process and are left behind as bone cells or osteocytes (fig. 314A). The osteocytes within their respective lacunae tend to be located between the layers of bony material (fig. 314A-D).

After the primary trabeculae of spongy bone are formed, the surrounding mesenchyme, which encloses the site of bone formation, becomes converted into a membranous structure, known as the periosteum. The cells of the inner layer of periosteum are transformed into osteoblasts and begin to deposit successive layers of compact bone around the initial framework of spongy bone (peripheral growth). The latter activity results in an increase in diameter of the bony area.

The first bone thus formed occurs in a restricted area. As the bone grows, the previously formed bone is torn down and resorbed, while new compact bone is built up around the area occupied by the spongy bone. Either by the



formation of new cellular entities or by the fusion of osteoblasts, multinucleated giant cells appear which aid in the dissolution of the previously formed bone. These multinucleate cells are known as osteoclasts (fig. 314H). The marrow-filled spaces between the trabeculae of spongy bone contain blood spaces (sinusoids), developing red blood cells, looser connective tissues, and fat cells (fig. 314H). When the trabeculae of spongy bone are resorbed, the marrow-filled area increases in size.

b. Endochondral and Perichondrial (Periosteal) Bone Formation

While membranous bone development utilizes collagenous fibrils and ossein as a foundation upon which the osteoblasts deposit bone salts, endochondral that is, intracartilaginous bone development employs small spicules or larger masses of cartilage as a basis for calcification. The small columns or spicules of cartilage are produced as a result of erosion and removal of cartilage. This erosion of cartilage is produced by perichondrial cells and vascular tissue which invade the cartilaginous substance from the perichondrium.

1) Endochondral Bone Formation. Endochondral bone formation occurs as follows:

(a) The initial step in erosion of cartilage is the migration within the cartilage, in a manner not understood, of the scattered cartilage cells. This migration brings about the arrangement of the cartilage cells and their capsules into elongated rows (fig. 314F). Some deposition of calcium within the cartilaginous matrix occurs at this time.

(b) As this realignment of the cartilage cells is effected, vascular buds from the inner layer of the perichondrium invade the cartilage, eroding the cartilaginous substance and forming primary marrow cavities (figs. 31 3D; 314E, F). Large multinucleate cells or chondroclasts make their appearance at this time and aid the process of dissolution of cartilage.

(c) Following this procedure, osteoblasts arise within the peripheral areas of each vascular bud and begin to deposit bone matrix upon the small spicules of calcified cartilage which remain. (See spicule “a,” fig. 314F.) The continual deposition of bone salts around these spicules converts the greatly eroded cartilaginous mass into spongy or cancellous bone (fig. 314F).

2) Perichondrial (Periosteal) Bone Formation. As cancellous bone is formed within the cartilaginous mass, the surrounding perichondrium of the original cartilage now becomes the periosteum, and the cells of the inner layer of the periosteum deposit circumferential layers of compact bone (perichondrial or periosteal bone formation) around the periphery of the cancellous bone (fig. 314F). The latter action forms a cylinder of compact bone around the spongy variety and around the cartilage which is being displaced (fig.



314F). The primary marrow spaces, established by the original invasion of the perichondrial vascular buds, merge to form the secondary marrow areas of the developing bone. This merging process is effected by the dissolution of previously formed bony spicules or trabeculae.

c. Conversion of Cancellous Bone into Compact Bone

Spongy or cancellous bone is converted into compact bone by the deposition of layers of compact bone between the trabeculae or columns of spongy bone, thus obliterating the marrow cavities around the trabeculae of the cancellous bone and converting the intervening areas into Haversian systems (fig. 314C, D).

D. Development (Morphogenesis) of the Endoskeleton

1. Definitions

For pedagogical purposes, the hard, skeletal tissues may be divided into the external skeleton or exoskeleton and the internal skeleton or endoskeleton. The exoskeleton comprises all the hard, protective structures which are derived from the mesenchyme of the dermis and from the epithelium of the epidermis, described in Chapter 12. The exoskeleton as a whole will not be described further.

Excluding the cxoskeleton and the softer, connective-tissue portion of the skeletal tissues, we shall proceed with a description of the morphogenesis of the main skeletal support of the vertebrate body, the endoskeleton. The endoskeleton is composed of the axial skeleton and the appendicular skeleton. The axial skeleton is composed of the skeleton of the head, the skeleton of the trunk, and the skeleton of the tail. The skeleton of the appendages is made up of the pectoral and pelvic girdles and the bony supports for the appendages.

2. Morphogenesis of the A\ial Skeleton a. General Features of the Skeleton of the Head

The cranium or skeleton of the head comprises:

( 1 ) the protective parts for the special sense organs and the brain, and

(2) the skeleton of the oral area and anterior end of the digestive tract.

That portion of the cranium which protects the brain and its associated, special sense organs may be called the skull, cranium proper, or neurocranium (fig. 3 1 5D) , whereas that which surrounds the anterior portion of the digestive tract and pharyngeal area is known as the visceral skeleton or splanchnocranium (fig. 315D).





Fig. 315. Developmental stages of the chondrocranium in the dogfish, Squalus acanthias. (A and B redrawn from El-Toubi, ’49, Jour. Morph., 84.) (A) Early de velopmental stage, 37-mm. embryo, lateral view. (B) Intermediate stage, 45-mm. embryo, lateral view. (C) Branchiostcgal (gill support) rays attached to ceratobranchial segment of gill arch. (D) Adult stage of chondrocranium (ncurocranium plus splanchnocranium), lateral view.

1) Neurocranium or Cranium Proper. The ncurocranium is present in three main forms in the vertebrate group:

(1) a complete cartilaginous cranium without dermal reinforcing bones, as in cyclostomatous and elasmobranch fishes (fig. 315D),

(2) an inner cartilaginous cranium, associated with an outer or surrounding layer of bony plates, as in Amia (fig. 316C, D), the adult skull of Necturus and the frog being similar but slightly more ossified (fig. 317B, C), and

(3) an almost entirely ossified cranium, in teleosts, reptiles, birds, and mammals (figs. 318C; 319C, D, E).

Various degrees of intermediate conditions exist between the above groupings.

2) Visceral Skeleton or Splanchnocranium. The splanchnocranium or visceral skeleton consists of a number of cartilaginous or bony arches which tend to enclose the anterior portion of the digestive tube (fig. 315D). They are present in pairs, one arch on one side, the other arch on the other side. The first two pairs are related to the skull in gnathostomes. The succeeding pairs of visceral arches arc associated with the branchial or gill apparatus in fishes and in certain amphibia, such as Necturus.

3) Development of the Skull or Neurocranium. The neurocranium of all vertebrates from the fishes to the mammals possesses a beginning cranial con

Fig. 316. Developmental stages of neurocranium of the bowfin, Amia calva. (A and B redrawn from De Beer, ’37, after Pehrson; C and D from Allis, 1897, J. Morph., 12.) (A) Ventral view of 9.5-mm. stage. (B) Dorsal view of 19.5-mm. stage. (C)

Cartilaginous neurocranium of adult stage. (D) Dermal (membrane) bones overlying neurocranium of adult stage. Cartilage == coarse stipple; bone = fine stipple.




dition in which dense mesenchyme, the so-called desmocranium, comes to surround the brain and its appendages. The membranous cranium is more pronounced in the basal areas of the brain. This pre-cartilage stage is followed by formation of cartilage which results in the development of a chondric neurocranium. A complete cartilaginous neurocranium is not formed in all vertebrate groups, although the ventro-lateral areas of all vertebrate skulls are laid down in cartilage. This basic, chondrocranial condition exists as the first step in skull formation, and it consists of three main regions, composed of cartilaginous rudiments (figs. 316A, 320):

( 1 ) The basal plate area is composed of a pair of parachordal cartilages on either side of the anterior extremity of the notochord, together with the otic capsules, surrounding the otic (ear) vesicles.

(2) A trabecular or pre-chordal plate area lies anterior to the notochord. This area begins at the infundibular-hypophyseal fenestra and extends forward below the primitive forebrain. Two elongated cartilages, the trabecula cranii (fig. 320A) or a single elongated cartilage (fig. 320B), the central stem or trabecular plate, develop in the basal area of this region. With the trabecular area are associated the sphenolateral, orbital or orbitosphenoidal cartilages and the optic capsules. The latter are placed in a position lateral to the orbitosphenoidal cartilages.

(3) A nasal capsular or ethmoidal plate area, associated with the developing olfactory vesicles, later arises in the anterior portion of the trabecular region (figs. 316A, 319A).

This fundamental cartilaginous condition of the vertebrate skull or neurocranium is followed by later conditions which proceed in three ways: (a) In the elasmobranch fishes, an almost complete roof of cartilage is developed, and the various cartilaginous elements fuse to form the cartilaginous neurocranium (fig. 315). This neurocranium enlarges but never becomes ossified, (b) In the ganoid fish, Amia, the frog, Rana, the mud puppy, Necturus, etc., the basic, ventrolaterally established, cartilaginous neurocranium is converted into a more or less complete chondrocranium by the formation of a roof and the complete fusion of the various eartilaginous elements (figs. 316A-C; 317A, B). In these forms, the cartilaginous cranium becomes ossified in certain restricted areas. In addition to this cartilaginous neurocranium, superficial, membrane bones (dermal bones) are added to the partially ossified chondrocranium. These membrane bones come to overlie and unite with the partly ossified cartilaginous skull (figs. 316D; 317C). (Consult also Table 1.) The adult skull or neurocranium in these forms thus is composed of a chondrocranial portion and an osteocranial part, the osteocranial part arising from cartilaginous and membranous sources, (c) In reptiles, birds, mammals, and



in many teleost fishes, the basic ventro-lateral regions of the cartilaginous neurocranium only are formed (figs. 318A, B; 319A, B). This basic chondrocranium undergoes considerable ossification, forming cartilage bones, which replaces the cartilage of the chondrocranium. These cartilage bones are supplemented by superficially developed membrane bones which become closely associated with the cartilage bones. The adult skulls of these vertebrates are highly ossified structures, composed of cartilage and membrane bones. (See Tables 2 and 3.) A few cartilaginous areas persist in the adult skull, more in teleost fishes than in the reptiles, birds, and mammals (Kingsley, ’25 and De Beer, ’37).

4) Vicissitudes of the Splanchnocranium. The early visceral skeleton, established in the embryo, experiences many modifications in its development in the different vertebrate groups.

In the elasmobranch fishes, the first visceral (mandibular) arch on either side gives origin to an upper jaw element, composed of the palatoquadrate (pterygoquadrate) cartilage, and a lower jaw element or Meckel’s cartilage





Fig. 317. Developmental stages of neurocranium in the frog. (A and B redrawn from De Beer, ’37, after Pusey; C, redrawn and modified from Marshall, 1893, Vertebrate Embryology, New York, Putnam’s Sons.) (A) Intermediate condition between larval and adult form. (B) Adult form of cartilaginous cranium, present after metamorphosis. (C) Adult neurocranium composed of membrane and cartilage bones associated with basic cartilaginous neurocranium (see Table 1). Cartilage == coarse stipple; bone = fine stipple.



Beer, ’37, from De Beer and Barrington.) (A) Dorsal view of 8 Vi -day stage of Anas (duck). (B) Lateral view of 14-day stage of Anas. (C) Lateral view, adult stage of Callus (chick). Cartilage = coarse stipple; bone — fine stipple.

(fig. 315D). Each second visceral (hyoid) arch in the shark forms on each side an upper hyomandibula, attached to the otic capsule by fibers of connective tissue, a ceratohyal part, and a lower basihyal element (fig. 315D). The basihyal portion of the two hyoid arches forms a basis for the so-called tongue. The succeeding branchial arches form supports for the gills and develop cartilaginous branchial rays which extend out into the gill area (fig. 315C). Each branchial arch on each side divides into four cartilages, namely, the upper pharyngobranchial, and the lower hypobranchial, the epibranchial and the ceratobranchial elements. The last two elements lie between the first two, and the ceratobranchial element is articulated with the hypobranchial element (fig. 315D).

The visceral skeleton in ganoid and teleost fishes arises similarly to that in elasmobranchs but becomes largely ossified in the adult (fig. 316).

In the frog, the well-developed, visceral skeleton of the late larva becomes greatly modified during metamorphosis and the acquisition of adulthood. The hyoid arch persists in cartilage. The mandibular arch contributes to the formation of the upper and lower jaws. The lower jaw in the metamorphosed frog consists of Meckel’s cartilages, reinforced by membrane bones, the dentaries and the angulospenials. The pterygoquadrate cartilages remain as cartilage and are reinforced by the pterygoid, quadratojugal, squamosal, maxillae and premaxillae, to form the upper jaw (fig. 317B, C and Table 1).

In birds, the first visceral or mandibular arch contributes to the formation of the quadrate and articulare at the angle of the jaw. These two bones on



either side represent cartilage bones. (See Table 2.) The hyoid and first branchial-visceral arches form the complicated support for the tongue (consult Table 2).

In mammals, the visceral arches contribute as much to the adult condition as in other higher vertebrates. In the human, the caudal portion of the vestigial upper jaw rudiment persists as the incus, and the caudal portion of Meckel’s cartilage contributes to the formation of the malleus. The mandibular arch thus contributes to the important ear bones (fig. 319C-2). The upper portion of the hyoid arch probably forms the stapes; the ventral portion forms one half of the hyoid bone; and the intervening tissue of the primitive hyoid arch contributes to the formation of the stylohyal structures (fig. 319C, D). The third arch on each side forms the greater horn of the hyoid; the fourth contributes to the thyroid cartilage; the fifth pair forms the arytenoid and cricoid cartilages (fig. 319C and Table 3).

b. Ossification Centers and the Development of Bony Skulls

The formation of the bony crania of all vertebrates entails the use of centers of ossification which involve methods of bone formation previously described. As a rule, one ossification center arises in a single bone, with the exception of those bones, such as the human frontal, sphenoid, or occipital bones, which result from the fusion of two or more bones. In these instances separate centers of ossification are developed in each individual bone. The exact number of ossification centers in all bones has not been exactly determined.

c. Development of the Axial Skeleton

1) Axial Skeleton of the Trunk; a) Notochord. The notochord is one of the basic structural features of the chordate group of animals. It will be recalled (Chapters 9 and 10) that the primitive notochordal band of cells is the physiological instrument which effects much of the early organization of the developing body of the vertebrate embryo. Aside from this basic, apparently universal function in vertebrate development, the notochord later functions as a prominent feature in the development of the median skeletal axis. In the cyclostomatous fishes, a persistent, highly developed notochord, enclosed in elastic, and fibrous, connective-tissue sheaths, is found in the adult. The enveloping, connective-tissue sheaths establish a covering for the nerve cord above and for the blood vessels immediately below the notochord. Vertebrae are not developed, but in the cyclostomes (Petromyzontia) paired cartilaginous rods lie along either side of the nerve cord above (Goodrich, ’30, pp. 27, 28). In the Dipnoi and in the cartilaginous ganoids, such as Acipenser sturio, the notochord persists unconstricted by vertebral elements although supplemented by these structures. In the shark group and in teleost fishes in general, as well as in certain Amphibia, such as Necturus, the notochord is continuous but constricted greatly by the developing vertebral centra. In




Fig. 319. Developmental stages of mammalian neurocranium and splanchnocranium. (A) Human chondrocranium at end of third month viewed from above (from Keibel and Mall, 1910, Manual of Human Embryology, vol. I, after Hertwig’s model). (B) Same, lateral view, slightly modified. (C-1) Lateral view of adult skull showing visceral arch (splanchnocranial) derivatives. (C-2) Auditory ossicles (see fig. 319B). Malleus derived from caudal end of Meckel’s cartilage in lower jaw portion of mandibular visceral arch; incus from caudal end of maxillary process of mandibular arch; stapes from upper or hyomandibular portion of hyoid visceral arch. (D) Lateral view of cat skull and visceral arch (splanchnocranial) derivatives. (E) Human cranium, lateral view, at birth showing fontanels (from Morris, ’42, Human Anatomy, Philadelphia, Blakiston). Cartilage = coarse stipple; bone == fine stipple.


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Fig. 320. Diagrams of basic cartilaginous underpinning or foundation of the vertebrat neurocranium. (Somewhat modified from De Beer, ’37, after De Beer and Woodger. (A) Pisces. (B) Placental mammals. It is to be observed that the trabecula cranii ii the fish is represented by the central stem or trabecular plate in the mammal.

most amphibia and in the reptiles, birds, and mammals, the notochord tend: to be entirely displaced by the vertebrae, and its residual remains are restrictet within or between the vertebrae. In mammals, the residual remainder o the notochord constitutes the nucleus pulposus (pulpy nucleus) near th( center of the fibrocartilage of the intervertebral disc. In the human, accordin) to Terry, ’42, p. 288, the pulpy nucleus forms a “pivot round which the bodiei of the vertebrae can twist or incline.”

b) Vertebrae. Vertebrae, the distinct segments of which the spinal columi consists, arise from sclerotomic mesenchyme, derived from the ventro-mesia aspects of the various somites (fig. 252A-D). Potentially, this sclerotomu mesenchyme in each primitive segment becomes segregated into eight masses four on either side of the notochord. These eight masses or blocks of mesen chyme form the arcualia. The arcualia become arranged in relation to th( notochord and the developing intermuscular septa as indicated in figure 321 A These masses are designated as basidorsals and basiventrals, interdorsals anc interventrals. Thus there are two basidorsals, two basiventrals, two interdor sals, and two interventrals.

During the formation of the vertebra in mammals, the sclerotomic masse: within a primitive body segment become associated about the notochorda axis as indicated in figure 321J-L. It is to be observed that the arteries fron the dorsal aorta lie in an intersegmental position. This position represent the area of the myoseptal membrane, shown in figure 321 A. As the scle rotomic masses increase in substance, each mass on each side of the noto chord becomes divisible into an anterior area, in which the mesenchymal cell are less dense, and a posterior area, where the cells are closely aggregatec



(fig. 321 J). The less dense mesenchymal mass represents the rudiment of the interdorsal vertebral element, while the posterior dense mass of mesenchyme is the basidorsal element. As development proceeds, the basidorsal mass of cells from one segment and the interdorsal mass of the next posterior segment on either side of the notochord move toward each other and align themselves in the intersegmental area as shown in figure 32 IK, L. The basidorsal element thus comes to lie along the anterior portion of the intersegmental area, and the interdorsal rudiment occupies the posterior part of this area. The four vertebral elements, two on either side of the notochord in the intersegmental area, form the basic vertebral rudiments, although rudimentary basiventral and interventral elements possibly are present. The intersegmental artery eventually comes to lie laterally to the forming vertebra.

Once these basic rudiments of the vertebra are established, the vertebra begins to form. In doing so, there is an increase in the number of mesenchymal cells present, and the sclerotomic masses move toward and around the notochord in the intersegmental position. The two dense basidorsal elements from either side expand dorsally around the neural tube as the two interdorsal rudiments coalesce to form the body of the centrum (fig. 321M). Laterally, the rudiment of the rib arises as a condensation of mesenchyme continuous with the forming neural arch and centrum. The rib element continues to grow ventro-laterally, particularly in the thoracic area (fig. 321N). In the lateral growth of the rib rudiment, surrounding mesenchyme is organized and incorporated into the growing structure of the rudiment.

Once the vertebral rudiment is established as a dense mass of mesenchyme, the pre-cartilage stage of cartilage development occurs (fig. 313A). The precartilage stage is followed soon by cartilage (fig. 313B, C). Later, centers of ossification arise as indicated in figure 3210, and the cartilaginous condition becomes converted into a bony condition. Secondary centers of ossification, forming bony epiphyses, ultimately arise after birth at the anterior and posterior ends of each centrum. When the ultimate size of the vertebra is attained, the epiphyseal cartilages between the epiphyses and the centrum of each vertebra become ossified, and the epiphyses thus unite with the centrum. The intervertebral discs of fibrocartilage form in the segmental position between the vertebrae.

It is to be observed that the intersegmental arrangement of the vertebrae permits direct passage of the spinal nerves to the developing musculature within each segment and also permits the musculature of each segment to attach itself to two successive vertebrae. The latter feature is particularly advantageous in lateral bending movements, so prominent in the swimming movements of water-dwelling forms.

See legend, fig. 321, for vertebral development in various vertebrates.

c) Divisions of the Vertebral Column. In fishes, two main divisions of the vertebral column are recognizable, the caudal region where the ver



Fig. 321. Development of vertebrae. The vertebral column in the phylum Vertebrata is a variable structure. In the early embryo the primitive notochord serves as the primitive axis. Later this structure develops fibrous sheaths in fishes and amphibia. The notochord plus its surrounding sheaths serves as the only axial support in the embryo and adult stages of Amphioxiis and Cyclostomes. However, in all true vertebrates, the notochord is supplemented during later embryonic stages by vertebral rudiments known as arcualia (fig. 321, A). Eight arcualia are present typically in each vertebral segment. The arcualia begin as mesenchymal condensations from the sclerotome (see fig. 252, A~D), and later are transformed into cartilaginous masses. In the elasmobranch fishes the cartilaginous arcualia fuse to form the vertebra as described below, but in most vertebrates they undergo ossification.

I. The Formation of Vertebrae in Fishes. In certain instances among the fishes, the arcualia are merely saddled on to the notochord and its sheaths. This condition is found, for example, in the lung fishes and cartilaginous ganoid fishes (fig. 321, E). A vertebral centrum is not developed in these instances.

In the elasmobranch fishes the vertebra is formed essentially from that group of arcualia known as the ba.saiia, that is, the basidorsals and basiveiitraL. These rudiments invade the fibrous sheath from above and below on either side and form the neural arch and centrum as indicated in fig. 321, C. The interbasalia — that is, the intcrdorsals and inlerventrals — lie between the vertebrae. The notochord is constricted greatly in the region of the centrum but is disturbed little in the areas between the centra. That is, the centrum is hollowed out or deeply concave at either end. This form of centrum is found in all amphicoelous vertebrae (fig. 321, P). In the tail region (fig. 321, C'), there are two vertebrae per muscle segment. This condition is known as diplospondyly. Other cartilaginous elements may enter into the formation of the centrum as indicated in fig. 321, C'.

The diplospondylous condition in the tail region of Amia presumably is developed as indicated in fig. 321, H'. In the trunk region of Amia the arcualia associate to form the vertebrae as in fig. 321, H. A certain amount of membrane bone may enter into the composition of the centra in Amia. In the teleost fishes (fig. 321, I), the basidorsals form the neural arches, but the centrum is developed almost entirely from the ossification of fibrpus connective tissue membrane (i.e., membrane bone formation). The basiventrals form the area of attachment of the pleural ribs and also form the hemal arches.,

II. Development of Vertebrae in Amphibia. In the frog (fig. 321, B), the neural arch of each vertebra appears to arise as the result of fusion and ossification of two basidorsal arcualia. Ossification spreads from the neural arch downward into the developing centrum. The centrum, however, develops as a result of perichordal ossibeation which arises within the membranous connective tissue around the notochord. The rudimentary interdorsals and interventrals probably grow inward into the intercentral spaces to obliterate the notochord between the centra. The interdorsal-interventral complex fuses ultimately with the caudal end of the centrum, to form a rounded knob which articulates with the concave end of the next posterior vertebra. That is, the vertebrae in the frog are procoelous (fig. 321, Q). The urostyle of the frog probably represents a fusion of rudimentary vertebrae caudal to the ninth or sacral vertebra. Vestigial notochordal remains may exist in the center of each bony centrum.

The development of the vertebrae in Necturus (fig. 321, D), resembles that of the frog, with the exception that the bony centrum arises from a perichordal ossification which is entirely independent of the neural arch. Also, the notochord remains continuous, being constricted in the region of the bony centrum, but relatively unconstricted in the area between the centra. That is, the vertebrae are of the amphicoelous type (fig. 321, P). The basiventral arcualia unite to form the hemal arches in the tail.

III. Development of Vertebrae in the Chick and Mammals. The development of the vertebra in the chick is a complicated affair, as the vertebra is composed of a complex of fused arcualia associated with a perichordal ossification (see fig. 321, F). The vertebrae are heterocoelous, their ends being partly procoelous and opisthocoelous. In mammals



tebrae possess hemal arches and the trunk region without hemal arches but with ribs. The amphibia begin to show a third division, the cervical area or anterior portion of the trunk region in which the vertebrae do not possess ribs. This area is limited to one vertebra, the axis. In the amphibia, also, a sacral region begins to make its appearance. It is only slightly differentiated in waterabiding forms but well developed in the Anura. The caudal vertebral area in the Anura generally is fused to form the coccyx or urostyle. The reptilian vertebral column manifests great variability in the different orders. The turtles show cervical, trunk, and tail regions, with the trunk vertebrae fused with the bony plates of the carapace. In snakes, a short cervical area, a greatly elongated trunk region, and a caudal area are present. Some of the snakes possess the largest number of vertebrae among verterbates, the number reaching several hundreds. Sacral vertebrae are absent in snakes. The lizards and crocodilians show conditions closely resembling the amphibia. In the birds, caudal, synsacral, thoracic, and cervical regions are present, while, in mammals, cervical, thoracic, lumbar, sacral, and caudal regions exist.

d) Ribs. Ribs are not found in cyclostomatous fishes. In the gnathostomes, two types of ribs may be present:

(1) dorsal ribs and

(2) ventral or pleural ribs.

Fig. 321 — (Continued)

the vertebra appears to arise from two basidorsal and two interdorsal arcualia as indicated in fig. 321, G. The origin of the basidorsal and interdorsal vertebral rudiments from the sclerotomic mesenchyme are shown in figure 321, J-M. The vertebrae are of the acoelous (amphiplatyan) type (fig. 321, S). The chevron bones and hemal arches in the tail region of many mammals represent basiventral elements. Fig. 321, M-O, shows the rib outgrowths from the developing vertebrae. Observe centers of ossification in the vertebra in fig. 321, O.

Fig. 321, A, presents a lateral view of the so-called arcualia in relation to the notochord and the myosepta (myocommata). According to this theory of the development of the vertebrae, the arcualia form the main rudiments from which future vertebrae arise. (B) The adult frog vertebrae showing probable contributions of arcualia. (C and C) Probable contributions of the arcualia to trunk and tail vertebrae of Squalus acanthias. (D) The adult vertebrae of Necturus maculosus. (E) The role played by the arcualia in forming the axial supporting structure in Acipenser sturio. (Redrawn and modified from Goodrich, Vertebrate Craniata, 1909.) (F) The composite origin of the vertebra in

the bird. (Redrawn from Piiper, 1928. Phil. Trans. Series B, 216.) (G) Probable con tributions of the arcualia to vertebra formation in man. (H) Probable contributions of the arcualia in the formation of trunk and caudal vertebrae in Amia calva. (I) Same for the teleost, Conodon nobilis. (J-L) The origin and early development of the sclerotomic mesenchyme in the mammal. (M) shows vertebral and costal development in a 15-mm. pig embryo. (N) presents vertebral and costal development in a human embryo of 11 mm. The vertebral and rib rudiments are in the mesenchymal stage at this period. (Redrawn from Bardeen, 1910. Keibel and Mall, Vol. I, Human Embryology, Lippincott, Phila.) (O) is a drawing of developing vertebra in the 22-mm. opossum embryo. (P, Q, R, and S) are diagrams of amphicoelous, procoelous, opisthocoelous and slightly biconcave amphiplatyan (acoelous) vertebrae. (Redrawn and modified from Kingsley, ’25.)



Ribs develop in relation to the basidorsal and basiventral elements and extend outward in the myosepta. The dorsal rib appears typically in the position between the epaxial and hypaxial divisions of the primitive skeletal musculature, whereas the pleural rib lies in close relationship to the coelomic cavity (fig. 31 IB). It is questionable whether or not the hemal arch, when present, is homologous with the ventral or pleural ribs. The shark, Squalus acanthias, has dorsal ribs. This condition is true also of all Tetrapoda. In Amia, the ribs are of the pleural variety, whereas, in most teleosts, pleural ribs are present, supplemented by dorsal or epipleural ribs.

Fig. 322. Development of the sternum in the mammal. (A and C redrawn from Hanson, ’19, Anat. Rec., 17; B redrawn from Kingsley, ’25.) (A) Diagrammatic recon struction of sternum of 24-mm. pig embryo. The two precartilaginous condensations of the mesosternum are united anteriorly with the presternal condensation. The rib or costal condensations are approaching and uniting with the sternal condensations. (B) Schematic representation of sternal rudiments in the mammal. The mesosternal cartilages have segmented into cartilaginous segments or slernebrae. Bilateral centers of ossification arise in each sternebra which later form the bony sternebra. (C) Sternum of old boar, weight 450 lbs. It is to be observed that the sternebrae have remained distinct, and in two of the sternal segments anterior to the xiphisternum the two centers of ossification produce a dual condition within the sternal segment. In the human and certain other mammals the sternebrae fuse to form the gladiolus or corpus sterni.



As indicated above, ribs may be considered as outward extensions or processes of the vertebrae. In the frog, the much-abbreviated ribs become firmly ossified to the basidorsal elements of the vertebrae and extend outward as the transverse processes. However, in most vertebrates, they are articulated with the vertebrae by means of lateral extensions or processes from the vertebrae.

Chondrification of the rib occurs separately from the chondrification of the vertebra, and articulations develop between the rib and the vertebrae (fig. 3210). Similarly, when ossification develops, a separate center of ossification arises in the body of the rib (fig. 3210). However, epiphyseal centers arise in the tubercular and capitular heads, which later unite with the shaft of the rib. The student is referred to Kingsley, ’25, for a full discussion of vertebrae and ribs.

e) Sternum. A sternum connected with the ribs, and thus forming a part of the protective thoracic basket, is found only in reptiles, birds, and mammals. A sternum is absent in the gymnophionan Amphibia (Apoda), is reduced to a midventral cartilaginous series of bars in Necturus, and forms a part of the pectoral girdle in the frog (fig. 323C).

In its formation in the mammal, the sternum begins as a bilateral series of mesenchymal aggregations between the ventro-mesial ends of the clavicular and costal concentrations of mesenchyme (fig. 322A). These mesenchymal aggregations move toward the midline, form pre-cartilage, and then form cartilage. The median cartilaginous mass at the anterior end forms the presternum or episternum; the portion between the rib elements forms the mesosternum, and the posterior free area is the metasternum or xiphisternum (fig. 322B). In forms which have a clavicle, the latter articulates with the episternum. The anterior portion of the mesosternum unites ultimately with the presternum to form the rudiment of the manubrium. The mesosternum segments into blocks or stemebrae, while the caudal free end of the sternum forms the xiphisternum (fig. 322C). Centers of ossification arise in these areas and convert them to bone. In the human, the stemebrae of the mesosternum unite to form the body or corpus sterni, but, in the cat, pig, and many other mammals, they remain distinct.

2) Axial Skeleton of the Tail. The axial skeleton of the tail is modified greatly from that of the trunk region. In water-living vertebrates, the tail forms a considerable portion of the body. As the tail is used for swimming purposes, the contained vertebrae are developed to serve this end. In consequence, rib processes are reduced or lost entirely, and hemal arches for the protection of the caudal blood vessels are strongly developed features. Another feature subserving the swimming function is the tendency toward diplospondyly, i.e., the development of two vertebral centra per segment (fig. 32 IH'). In land forms, the tail tends to be reduced. However, in the armadillo, kangaroo, etc., the tail is a formidable structure, and hemal-arch

Fig. 323. Pectoral and pelvic girdles. (A) Diagrammatic pectoral girdle of Tetrapoda (modified from Kingsley, ’25). (B) Pectoral girdle of Squalus acanthias. (C) Pectoral

girdle of the frog, Rana (redrawn from Kingsley, ’25, after Parker). Observe that clavicle is a small bony bar superimposed upon procoracoid; suprascapula removed on right side. (D) Pectoral girdle of the bird. Callus. (E) Human pectoral girdle. (F) Diagrammatic representation of pelvic girdle in Tetrapoda (modified from Kingsley, ’25). (G)

Pelvic girdle in Squalus acanthias. (H) Pelvic girdle in Rana cateshiana. (1) Pelvic girdle in Callus (chick). (J) Pelvic girdle in human. (K) Pelvic girdle in Didelphys (opossum). (L) Dorsal view of sacrum and pelvic girdle in the armadillo, Tatusia.




structures for the protection of blood vessels are developed in the intervertebral area.

d. Development of the Appendicular Skeleton of the Paired Appendages

1) General Features. Two types of appendages are found in the vertebrate group:

(1) median unpaired appendages which take their origin in the median plane and

(2) paired bilateral appendages which arise from the lateral surface of the body.

Median appendages appear in the fishes, aquatic urodeles, and. in the larval form of anuran amphibia. They also occur in the crocodilian and lizard groups, among the reptiles, and, among mammals, in the whales.

All appendages arise as outgrowths of the body. The median appendages or fins of fishes possess separate skeletal structures for support, but the median, fin-like structures in the tails of amphibia, reptiles, and whales do not acquire a separate internal skeleton. All fishes possess a median caudal or tail fin at the terminus of the tail, a median anal fin posterior to the anal area, and one or more median dorsal fins.

Most vertebrates possess two pairs of bilateral appendages (Chap. 10, p. 508), one pair located anteriorly in the pectoral or breast region and the other pair situated posteriorly in the pelvic area just anterior to the anus. Each paired appendage has a skeleton composed of two parts:

( 1 ) a girdle component and

(2) a limb component.

The girdle component of each appendage is associated with the axial skeleton of the trunk and also with the girdle component of the appendage on the contralateral side. The entire girdle of each pair of appendages thus tends to form a U-shaped structure with the closed portion placed ventrally (fig. 323 A-K). In fishes, the open dorsal area of the U-shaped girdle in the pectoral area may be closely associated with the axial skeleton, but, in land forms, it is the pelvic girdle which joins the axial skeleton. This relationship is to be expected, for, in fishes, the tail is the more important propulsive mechanism, the head region being the “battering ram” insinuating itself through the water. As a result, the skull, anterior vertebrae, and the pectoral girdle ofttimes form a composite structure as, for example, in many teleost fishes. In land-living vertebrates, on the other hand, the main propulsive force is shifted anteriorly from the tail region and is assumed to a great extent by the posterior pair of appendages. In consequence, the pelvic girdle acquires an intimate relationship with the axial skeleton, and a fusion of vertebrae to form the sacrum occurs. The sacrum serves as the point of articulation be



tween the pelvic girdle and the axial skeleton and is most highly developed in those species which use the hind limbs vigorously in support and propulsion of the body (fig. 3231, L).

Two main types of bilateral appendages are found in the vertebrate group:

( 1 ) the ichthyopterygium of Pisces and

(2) the cheiropterygium of Tetrapoda.

The former is flattened dorso-ventrally, and assumes the typical flipper or fin shape, while the latter is an elongated, cylindrical affair. /

2) Development of the Skeleton of the Free Appendagk^The paired appendages arise either as a dorso-ventrally flattened fold of the epidermal portion of the skin, or as a cylindrical outgrowth of the epidermis. (See Chap. 10.) Within the epidermal protrusion, is a mass of mesenchyme (figs. 262D, E; 324A). As development proceeds, condensations of mesenchyme, centrally placed, begin to foreshadow the outlines of the future skeletal structures of the limb (fig. 324A, C, D). This mesenchyme gradually becomes more compact to form a pre-cartilage stage, to be followed by a cartilaginous condition.

The pattern, which these cartilages of the limb assume, varies greatly in the two types of limbs mentioned above. In the ichthyopterygium (fig. 323B, G), they assume a radially arranged pattern, extending out from the point of attachment to the girdle, whereas, in the cheiropterygium (fig. 323A), they assume the appearance characteristic of the typical limb of the Tetrapoda.

In the tetrapod limb, such as that of the hog, chick, or human, elongated, cylindrically shaped bones begin to make their appearance in mesenchyme (fig. 324A-E). Following the cartilaginous condition, a center of ossification arises in the shaft or diaphysis of each developing bone, transforming the cartilage into bone (figs. 314E, F; 324E). Cancellous or spongy bone is formed centrally within the shaft, while compact bone is deposited around the periphery of the shaft (fig. 314E, F). Later, the cancellous bone of the shaft is resorbed, and a compact bony cylinder, containing a relatively large marrow cavity, is formed. Separate centers of ossification, the epiphyses, arise in the distal ends of the bones (fig. 3241). Each epiphysis is separated from the bone of the shaft by means of a cartilaginous disc, the epiphyseal cartilage (fig. 3241). At maturity, however, the bony epiphysis at each end of the bone becomes firmly united with the shaft or diaphysis by the appearance of an ossification center in the epiphyseal cartilage (fig. 324J). Internally, the ends of the long bones tend to remain in the cancellous or spongy condition, whereas the shaft is composed of compact bone with an enlarged central marrow cavity (fig. 324J). For later changes of the bony substance involved in the growth of bone, see growth of bone, p. 693.

3) Formation of the Girdles. The typical tetrapod pectoral girdle (fig. 323 A) is composed of a sternal midpiece, three lateral columns, extending


S'-r' % ':$ sWi I^S^J

F. G




Fig. 324. Development of long bones of the appendages. (B and E have been modified to show conditions present in the fore- and hind appendages at about 8 weeks. For detailed description of limb development consult Bardeen, ’05, Am. J. Anat., 4; Lewis, 02, Am. J. Anat., 2.) (A) Forelimb at II mm. (B) Forelimb at about eighth week,

showing centers of OKSsification in humerus, radius and ulna. (C) Hindlimb at 11 mm. (D) Hindlimb at 14 mm. (E) Hindlimb at about eighth week, showing centers of ossification in femur, tibia, and fibula.

The heavy strippling in A, C, D represent centers of chondrification; the black areas in B and E portray ossification centers within cartilaginous form of the long bones.

F-J represent stages in joint development.




dorsad from the sternal area on either side, the clavicle, procoracoid, and coracoid to which is attached dorsally the scapula. Often a suprascapula is attached to the scapula. The pelvic girdle of the Tetrapoda, on the other hand (fig. 323F), is composed of two lateral columns on either side. The anterior column is called the pubis, and the posterior column is the ischium. An ilium is attached to the dorsal ends of the pubis and ischium on either side. Epipubic and hypoischial midpieces are sometimes present at the midventral ends of the pubic and ischial columns in some species.

As in the development of the skeleton of the free appendage, all the rudiments of these structures are laid down in cartilage and later ossify, with the exception of the clavicle which may be of intramembranous origin (Hanson, ’20a and ’20b). The clavicles are more strongly developed in man, whereas the coracoidal elements are vestigial (fig. 323E). In the cat, the coracoidal and clavicular elements are reduced. However, in the chick and frog, the coracoidal elements are dominant (fig. 323C, D). In the pelvic girdle, the iliac, pubic, and ischial elements are constant features in most Tetrapoda. In the shark, a single coracoid-scapula unit is present in the pectoral girdle and the pelvic girdle is reduced to a small transverse bar of cartilage (fig. 323B, G).

e. Growth of Bone

Bone once formed is not a static affair, for it is constantly being remodeled and enlarged during the growth period of the animal. In this process, bone is destroyed arid resorbed by the action of multinucleate giant cells, called osteoclasts, or specialized, bone-destroying cells and is rebuilt simultaneously in peripheral areas by osteoblasts from the surrounding periosteal tissue.

To understand the processes involved in bone growth, let us start with the conditions found in the primitive shaft of a long bone (fig. 314F). Within the bony portion of the shaft, there is a network of cancellous bone, and, peripherally, there are lamellae of compact bone. The following transformative activities are involved in the growth of this bone:

(1) Within the bone, the cancellous columns of bony substance are destroyed by osteoclasts, the bony substance is resorbed, the marrow spaces are enlarged, while, peripherally, circumferential lamellae are deposited around the bones beneath the periosteum.

(2) Distally, cartilage is converted into cancellous bone while outer circumferential lamellae are fabricated beneath the periosteum. The bony substance thus creeps distally, lengthening the shaft of the bone.

(3) As the bone increases in length, some of the bony substance, forming the wall of the shaft or diaphysis is destroyed. This alteration is effected to a degree by vascular buds which grow into the bony substance from the periosteum around the outer surface of the bone and from the endosteum which lines the marrow cavities. These vascular



buds erode the bony substance with the aid of osteoclasts and produce elongated channels in the bone, channels which tend to run lengthwise along the growing bone. Once these channels are made, osteoblasts lay down bony lamellae in concentric fashion, converting the channel into an Haversian system. (Consult Maximow and Bloom, ’42, pp. 141-145.) The Haversian systems thus tend to run parallel to the length of the bone. The Haversian canals open into the central marrow cavity of the bone in some of the Haversian systems, whereas others, through Volkmann’s canals, open peripherally.

(4) While the foregoing processes are in progress, circumferential lamellae are laid down around the bone. The bone’s diameter thus grows by the erosion of its bony walls (including previously established Haversian systems) and by the formation of new bony substance externally around the diaphysial area which is destroyed and resorbed. New Haversian systems and new circumferential lamellae in this way supersede older systems and lamellae.

At the distal ends of the bone within the spaces of the cancellous bone, red marrow is found. In the shaft or diaphysis, however, the contained marrow cavity is filled with yellow bone marrow, composed mainly of fat cells.

The distal growth of elongated, cylindrically shaped bones, such as the phalanges or the long bones of the limbs, is possible, while epiphyseal cartilage remains between the shaft of the bone and the bony epiphysis at the end of the bone. The maintenance and growth of the epiphyseal cartilage is prerequisite to the growth of these bones, for the increase in the length of the bony shaft involves the conversion of cartilage nearest to the bony shaft into cancellous bone. A bony cylinder of compact bone is then formed around the cancellous bone. When, however, the epiphyseal cartilage ceases to maintain itself, and it in turn becomes ossified, uniting the epiphysis to the bony shaft, growth of the bone in the distal direction comes to an end. Growth in the length of a vertebra also involves the epiphyseal cartilages lying between the bony ends of the centrum and the epiphyses. Increase in size of the diameter of the vertebra results from the destruction and resorption of bone already formed and the deposition of compact bone around the periphery.

In the case of flattened bones of cartilaginous origin such as the scapula or the pelvic-girdle bones, growth in the size of the bone is effected by the conversion of peripherally situated cartilage into bone, and by the destruction and resorption of bone previously formed and its synchronous replacement external to the area of destruction. On the other hand, in the growth of flat bones of membranous origin, the bone increases in size along its margins at the expense of the connective tissue surrounding the bone. Growth in the diameter of membrane bones is similar to that of cartilage bone, namely, destruction, resorption, and deposition of new bone at the surface.



/. Formation of Joints

1) Definitions. The word arthrosis is derived from a Greek word meaning a joint. In vertebrate anatomy, it refers to the point of contact or union of two bones. When the contact between two bones results in a condition where the bones actually fuse together to form one complete bone, the condition is called ankylosis or synosteosis. If, however, the point of contact is such that the bones form an immovable union, it is called a synarthrosis; if slightly movable, it forms an amphiaithrosis; and where the contact permits free mobility, it is known as a diarthrosis. Various degrees of rapprochement between bones, therefore, are possible.

2) Ankylosis (Synosteosis) and Synarthrosis. In the development of the bones of the vertebrate skull, two types of bone contact are effected:

(1) ankylosis and

(2) synarthrosis.

In the human frontal bone, for example, two bilaterally placed centers of ossification arise in the connective-tissue membrane, lying below the skin in the future forehead area. These two centers increase in size and spread peripherally until two frontal bony areas are produced, which are separated in the median plane at birth. Later on in the first year following birth, the two bones become sutured (i.e., form a synarthrosis) in the midsagittal plane. Beginning in the second year and extending on into the eighth year, the suture becomes displaced by actual fusion of bone, and ankylosis occurs. In the cat, however, the two frontal bones remain in the sutured condition (synarthrosis). The temporal bone in the human and other mammals is a complex bone, arising by the ultimate fusion (ankylosis) of several bones. In the human at birth, three separate bones are evident in the temporal bone:

(1) a squamous portion,

(2) a petrous portion, and

(3) a tympanic part.

The squamous and the tympanic bones are of membranous origin, whereas the petrous portion arises through the ossification of the cartilaginous otic capsule. The fusion of these three bones occurs during the first year following birth. The occipital bone is another bone of complex origin. Five centers of ossification are involved, viz., a basioccipital, two exoccipitals, a squamous inferior, and a squamous superior. The last arises as a membrane bone; the others are endochondral. Ultimate fusion of these entities occurs during the early years of childhood and is completed generally by the fourth to sixth years. In the cat, the squamous superior remains distinct as the interparietal bone. Finally, the sphenoid bone in the human represents a condition derived from many centers of ossification. According to Bardeen, TO, fourteen centers of ossification arise in the sphenoidal area, ten of them



arising in the orbitotemporal region of the primitive chondrocranium. At birth, two major portions of the sphenoid bone are present, the presphenoid and the basisphenoid, being separated by a wedge of cartilage. Ultimate fusion of these two sphenoid bones occurs late in childhood (Bardeen, ’10). In the adult cat, they remain distinct. The maxillary bone in the human arises as a premaxillary and a maxillary portion; later these bones fuse to form the adult maxilla. In the cat, on the other hand, these two bones remain distinct. (Consult also Table 3.)

The history of the human skull, therefore, is one of gradual fusion (ankylosis) of bones. In many parts, however, fusion does not occur, and definite sutures (synarthroses) are established between the bones, as in the case of the two parietals, the parietal and the occipital, the frontal and the parietals, etc.

The formation of the association between the parietal bones and neighboring bones establishes an interesting developmental phenomenon, known as the fontanels. The fontanels are wide, membranous areas between the developing parietal and surrounding bones which, at birth, are not ossified. These membranous areas are the anterior fontanel, in the midline between the two parietals and two frontal bones, and the posterior fontanel, between the parietals and the occipital bones. The lateral fontanels are located along the latero- ventral edges of the parietal and neighboring bones (fig. 319E).

3) Diarthrosis. A diarthrosis or movable joint is established at the distal ends of the elongated, cylindrically shaped bones of the body. Diarthroses are present typically in relation to the bones of the appendages. As the bones of the appendages form, there is a condensation of the mesenchyme in the immediate area of the bone to be formed. At the ends of the bone, the mesenchyme is less dense than in the area where the rudimentary bone is in the process of formation (fig. 324A-E). As a result, the area between bones is composed of mesenchyme less compact and less dense than in the areas where bone formation is initiated (fig. 324F, G). This mesenchyme at the ends of the bones thus forms a delicate membrane, tying the bony rudiments together, and, as such, forms a rudimentary synarthrosis. As development proceeds, the miniature bone itself becomes more dense, and, eventually, cartilage is formed. The latter later is displaced gradually by bone (fig. 324E). The areas between the ends of the respective developing bones become, on the contrary, less dense, and a space within the mesenchyme is developed between the ends of the forming bones (fig. 324H). As this occurs, connective tissue, continuous with the periosteum, forms around the outer edges of the ends of the bones, tying the ends of the bones together (fig. 324H, I). A cavity, the joint cavity, thus is formed at the ends of the bones, bounded by the cartilage at the ends of the bones and peripherally by connective tissues or ligaments which tie the ends of the bones together along their margins. The membrane which lines the joint cavity is known as the synovial mem



brane, and the cartilaginous discs at the ends of the bones form the articular cartilages (fig. 324H, J).

4) Amphiarthrosis. The term amphiarthrosis refers to a condition intermediate between synarthrosis and diarthrosis. This condition occurs for example in the area of the pubic symphysis.

g. Dermal Bones

As observed in figure 31 lA, the primitive mesenchyme of the ghost skeleton of the embryo underlies the epidermal tube, as well as enmeshing the neural, gut, and coelomic tubes. As mentioned previously, wherever mesenchyme exists, a potentiality for bony or bone-like structures also exists. Consequently, it is not surprising that various types of dermal armor or exoskeletal structures in the form of bone, dermal scales, and bony plates are developed in various vertebrates in the dermal area, as described in Chapter 12. Aside from the examples exhibited in Chapter 12, other important bony contributions to the skeleton of vertebrates may be regarded as essentially dermal in origin. Among these are the membrane bones of the skull (Tables 1, 2, and 3 ) . These bones sink inward and become integrated with the basic chondrocranial derivatives to form a part of the endoskcleton. Other examples of membrane bones of dermal origin are the gastralia or abdominal ribs of the Tuatera (Sphenodon) and the Crocodilia, the formidable, dermal, bony armor of the Edentata, e.g., the armadillo, and the bony plates on the head, back, and appendages in certain whales (Kingsley, ’25, p. 17). All these examples of dermal armor or exoskeletal structures form an essential protective part of the entire hard or bony skeleton of vertebrate animals.


Baitsell, G. A. 1921. A study of the development of connective tissue in the Amphibia. Am. J. Anat. 28:447.

Bardeen, C R. 1910. Chap. XI. The development of the skeleton and of the connective tissues. Human Embryology, Edited by Keibel and Mall. J. B. Lippincott Co., Philadelphia.

Bell, E. T. 1909. II. On the histogenesis of the adipose tissue of the ox. Am. J, Anat. 9:412.

De Beer, G. R. 1937. The development of the vertebrate skull. Oxford University Press, Inc., Clarendon Press, New York.

Goodrich, E. S. 1930. Studies on the structure and development of vertebrates. Macmillan and Co., London.

Hanson, F. B. 1919. The development of the sternum in Sus scrofa. Anat. Rec. 17:1.

. 1920a. The development of the

shoulder-girdle of Sus scrofa. Anat. Rec. 18:1.

. 1920b. The history of the earliest

stages in the human clavicle. Anat. Rec. 19:309.

Jordan, H. E. 1939. A study of fibrillogenesis in connective tissue by the method of dissociation with potassium hydroxide, with special reference to the umbilical cord of pig embryos. Am. J. Anat. 65:229.

Kingsley, J. S. 1925. The Vertebrate Skeleton. P. Blakiston’s Son & Co., Philadelphia.



Lewis, W. H. 1922. Is mesenchyme a syncytium? Anat. Rec. 23:177.

Mall, F. P. 1902. On the development of the connective tissues from the connective-tissue syncytium. Am. J. Anat. 1:329.

Maximow, A. 1929. Uber die Entwicklung argyrophiler und kollagener Fasern in Kulturen von erwachsenem Saugetiergewebe. Jahrb. f. Morph, u. Mikr. Anat. Abt. II. 17:625.

and Bloom, W. 1942. A Textbook

of Histology. W. B. Saunders Co., Philadelphia.

Rasmussen, A. T. 1923. The so-called hibernating gland. J. Morphol. 38:147.

Shaw, H. B. 1901. A contribution to the study of the morphology of adipose tissue. J. Anat. & Physiol. 36: (New series, 16) :1.

Sheldon, E. F. 1924. The so-called hibernating gland in mammals: a form of adipose tissue. Anat Rec. 28:331.

Stearns, M. L. 1940. Studies on the development of connective tissue in transparent chambers in the rabbit’s ear. Part II. Am. J. Anat. 67:55.

Schreiner, K. E. 1915. Uber Kern- und Plasmaveranderungen in fettzellen wahrend des fettansatzes. Anat. Anz. 48:145.

Terry, R. J. 1942. The articulations. Morris’ Human Anatomy, Blakiston, Philadelphia.


Tke Muscular System

A. Introduction

1. Definition

2. General structure of muscle tissue

a. Skeletal muscle

b. Cardiac muscle

c. Smooth muscle

B. Histogenesis of muscle tissues

1. Skeletal muscle

2. Cardiac muscle

3. Smooth muscle

C. Morphogenesis of the muscular system

1. Musculature associated with the viscera of the body

2. Musculature of the skeleton

a. Development of trunk and tail muscles

1 ) Characteristics of trunk and tail muscles in aquatic and terrestrial vertebrates

a) Natatorial adaptations

b) Terrestrial adaptations

c) Aerial adaptations

2) Development of trunk and tail musculature

a) General features of myotomic differentiation in the trunk

b) Differentiation of the myotomes in fishes and amphibia

c) Differentiation of the truncal myotomes in higher vertebrates and particularly in the human embryo

d) Muscles of the cloacal and perineal area

e) Development of the musculature of the tail region

b. Development of muscles of the head-pharyngeal area

1) Extrinsic muscles of the eye

2) Muscles of the visceral skeleton and post-branchial area

a) Tongue and other hypobranchial musculature

b) Musculature of the mandibular visceral arch

c) Musculature of the hyoid visceral arch

d) Musculature of the first branchial arch

e) Muscles of the succeeding visceral arches

f) Muscles associated with the spinal accessory or eleventh cranial nerve

g) Musculature of the mammalian diaphragm

c. Development of the musculature of the paired appendages

d. Panniculus carnosus




A. Introduction

1. Definition

The muscular system produces mobility of the various body parts. As such, it is composed of cells specialized in the execution of that property of living matter which is known as contractility. Since contractility is a generalized property of living matter, it may occur without the actual differentiation of muscular tissue. In the developing heart of the chick, for example, contractures begin to occur as early as 33 to 38 hours of incubation before muscle cells, as such, have differentiated (Patten and Kramer, ’33).

2. General Structure of Muscle Tissue

Muscle cells are elongated, fibrillated structures, known as muscle fibers. They contain many elongated fibrils, called myofibrils, extending longitudinally along the muscle fiber. The myofibrils may possess a series of cross striations in the form of light and dark transverse bands as in skeletal or striated muscle and cardiac muscle, or the transverse bands may be absent as in smooth muscle (fig. 325 A-C). In smooth muscle, the myofibrils are extremely fine, whereas in striated muscle they are seen readily under the microscope.

a. Skeletal Muscle

In skeletal muscle, the muscle fibers are elongated, cylinder-shaped structures; the ends are rounded; and a row of nuclei extend along the periphery of the muscle fiber or cell, and are more numerous at the ends of the cell than in the central portion. The cell, as a whole, is filled with myofibrils, embedded in a matrix of sarcoplasm. The latter contains fat droplets, glycogen, interstitial granules, amino acids, mitochondria, and Golgi substances. The surrounding cell membrane is a delicate structure and is known as the sarcolemma.

The myofibrils are composed of dark and light transverse bands, a dark band alternating with a light band. The bands are arranged along the myofibrils in such a manner that the dark band of one fibril is at the same level as the dark bands of other fibrils. The light bands are arranged similarly. This arrangement presents the effect shown in figure 325A.

Two types of muscle fibers are found in skeletal muscle. In one type, the red or dark fiber, there is an abundance of sarcoplasm with fewer myofibrils. The myofibrils possess weaker transverse markings or striations. In the second type, the pale or white fiber, there is less of the sarcoplasm present with a larger number of highly differentiated myofibrils, having well-defined transverse striations. This muscle fiber is larger in transverse diameter than the red type. In many animals, such as man, these two sets of fibers are intermingled in the various skeletal muscles, but in some, such as the breast



muscles of the common fowl, the white fibers constitute most of the muscle. Also, in the M. quadratus femoris of the cat or the M. semitendinosus of the rabbit, the red fiber predominates. In general, the more continuously active muscles contain the greater number of red fibers, while the less continuously active contain pale fibers. Pale fibers react more quickly and thus contract more readily than the red fibers. However, they are exhausted more rapidly.

Connective tissue, mostly of the white fibrous variety, associates the muscle fibers (cells) into groups called muscles. Muscles, such as the Mm. biceps brachii, biceps femoris, sartorius, rectus abdominis, etc., are a mass of associated muscle fibers, tied together by connective-tissue fibers.

The surrounding connective tissue of a particular muscle is known as the external perimysium (fig. 325D). The external perimysium extends centralwaref into the muscle and separates it into smaller bundles of fibers, or fasciculi. Thus each fasciculus is a group of muscle fibers, surrounded by the internal perimysium. The perimysium around each fasciculus extends into the fasciculus between the muscle cells, where its fibers become associated with the sarcolemma of each muscle fiber (cell).

The connection between the muscle fibers and their tendinous attachment has attracted considerable interest. One view holds that the myofibrils pass directly into the tendinous fibers. An alternative and more popular view maintains, however, that it is the sarcolemma which attaches directly to the tendinous fibers. Hence, the pull of the muscle is transmitted through the sarcolemmas of the various muscle cells to the tendon.

b. Cardiac Muscle

Cardiac muscle is characterized by the presence of alternating dark and light bands as in skeletal muscle. The striations are not as well developed, however, as in skeletal muscle, nor is the sarcolemma around the muscle fibers as thick. Another distinguishing feature of cardiac muscle is the fact that the fibers anastomose and thus form a syncytium, although M. R. Lewis (T9) questions this interpretation. Still another characteristic structure of cardiac muscle is the presence of the intercalated discs (fig. 325C). These discs are heavy transverse bands which extend across the fiber at variable distances from one another. A final feature which distinguishes cardiac muscle is the central location of the nuclei within the anastomosing fibers.

c. Smooth Muscle

Smooth muscle fibers are elongated, spindle-shaped elements which may vary in length from about 0.02 mm. to 0.5 mm. The larger fibers are found in the pregnant uterus. The diameter across the middle of the fiber approximatess 4 to 7 /i. This middle area contains the single nucleus. The fiber



tapers gradually from the middle area and may terminate in a pointed or slightly truncate tip (fig. 325B).

Smooth muscle cells may contain two kinds of fibrils:

(1) fine myofibrils, presumably concerned with contraction phenomena, within the cytoplasm and

(2) myoglial or border fibrils, coarser than the myofibrils, in the peripheral areas of the cell.

The myoglial fibrils are not usually demonstrable in adult tissues.

A connective-tissue mass of fibers between the smooth muscle fibers which binds the fibers into bundles as in skeletal muscle is not readily demonstrated. It may be that a kind of adhesiveness or stickiness (Lewis, W. H., ’22) associates these muscle fibers into a mass, within which each muscle cell is a distinct entity and not part of a syncytium. However, around the muscle bundles, elastic and white fibers (Chap. 15) seem to hold the muscle tissue in place and some elastic fibers may be present between the cells, especially in blood vessels.

B. Histogenesis of Muscle Tissues 1. Skeletal Muscle

The primitive embryonic cell which gives origin to the later muscle cells is called a myoblast. The myoblasts which give origin to skeletal muscle fibers are derived from two sources:

(1) mesenchyme and

(2) myotomes.

(See Chap. 11 for origin of mesenchyme and myotomes; also consult fig. 252.)

In striated-muscle-fiber formation, the myoblasts begin to elongate and eventually produce cylinder-like structures. As the cell continues to elongate, the nuclei increase in number, and, hence, the myoblast becomes converted into a multinuclear affair in which the nuclei at first lie centrally along the axis of the cell. Later, the myofibrils increase, and the nuclei move peripherally.

As the myofibrils grow older, dark and light areas appear along the fibrils. These dark and light bands are shown in figure 325E. Observe that the light band is bisected by the slender membrane, known as Krause’s membrane, shown in the figure as the dark line, Z., and the dark band is bisected by Hensen’s membrane.

2. Cardiac Muscle

The musculature of the vertebrate heart takes its origin from the two mesial walls of hypomeric fnesoderm (i.e., the splanchnic layers of mesoderm) which come to surround the endocardial primordia or primitive blood capillaries


coursing anteriad below the foregut (Chap. 17). These two enveloping layers of mesoderm give origin to the epicardium and myocardium of the heart, and in consequence they are referred to as the epimyocardial rudiment. From the surfaces of the two layers of hypomeric mesoderm which face the primitive blood capillaries, mesenchymal cells are given off. These mesenchymal cells constitute the myocardial primordium. The outer wall of each hypomeric layer of mesoderm, however, retains its epithelial character and eventually gives origin to the epicardium or coelomic covering of the heart. The mesenchymal cells which form the myocardial primordium surround the two endocardial rudiments (blood capillaries) and later form an aggregate of coalesced cells, i.e., a syncytium. The future heart musculature arises from this syncytium.

As the mass of the myocardial syncytium increases in size, the nuclei become irregularly scattered, and myofibrils make their appearance. The number of myofibrils rapidly increases, and dark bands of anisotropic substance (i.e., substance which is doubly refractive under polarized light) alternate with lighter bands of isotropic substance. Z lines soon appear which bisect the lighter segment of the myofibrils.

The myofibrils increase, and the myocardial syncytium gradually becomes drawn out into elongated strands of cytoplasm which appear to anastomose (fig. 325C). The nuclei are scattered within these strands. As the myofibrils




mesenchyme gives:









^^^■interventral [ZZZI ®AS'VENTRAL J D.

Fig. 326. Arrangement of muscle tissues. (A) Ventricles of alligator heart, ventral aspect, showing spiral arrangement of superficial muscle layers. (Redrawn from Shaver, Anat. Rec., 29.) (B) Arrangement of smooth muscle layers of the stomach. (Redrawn

from Bremer, 1936, Textbook of Histology, Philadelphia, Blakiston, after Spalteholz. ) (C) Transverse section of tail of Squalus acanthias showing arrangement of epaxial and hypaxial muscle groups. (D) Primitive arrangement of myotomes into epaxial and hypaxial groups in relation to the myocommata or myosepta. Observe that the myoseptum attaches to the middle of the vertebra. (Redrawn and modified from Goodrich, Vertebrate Craniata, 1909, New York, Macmillan Co., and Kingsley, Comparative Anatomy of Vertebrates, 1912, Philadelphia, Blakiston.

continue to increase, they become aggregated into groups and are arranged in such a manner that the dark and light bands of adjacent fibrils form regular dark and light bands across the muscular strands. The intercalated discs finally make their appearance here and there across the muscle strands (fig. 325C). In some areas, there are no nuclei within the muscle strand between the intercalated discs.

3. Smooth Muscle

Smooth muscle, cells arise from mesenchyme. In doing so, the mesenchymal cells lose their stellate shapes, elongate, and eventually become spindle shaped. Accompanying these changes, the nuclei experience some extension in the direction of the elongating cells (fig. 325B). Fibrils appear in the cytoplasm, first at the periphery in the form of coarse fibers, to be followed somewhat later by the true myofibrils of finer texture. It is possible that the coarser fibrils, the so-called myoglial fibers, represent bundles of myofibrils. The



myofibrils in smooth muscle fibers do not assume anisotropic (dark) and isotropic (light) bands or cross striations. Increase in the number of muscle fibers (cells) appears to occur by the mitotic division of existing fibers and also by the transformation of other mesenchymal cells.

C. Morphogenesis of the Muscular System

1. Musculature Associated with the Viscera of the Body

The musculature associated with the viscera of the body is of the smooth type with the exception of cardiac muscle and anterior part of the esophagus. Smooth and cardiac musculature are under involuntary control. The smooth muscle tissue of the digestive tract is derived from mesenchyme, which arises from the inner or splanchnic layers of the hypomeres, while that of the urinary and genital systems takes its origin from nephrotomic mesoderm and contributions from the splanchnic layers of the two hypomeres (fig. 311 A, B). The smooth muscle tissue associated with many of the blood vessels of the body arises from mesenchymal sources in the immediate area of the blood vessels.

The arrangement of muscle tissue in various parts of the digestive tract, blood vessels, and urinary and reproductive ducts is generally in the form of circular and longitudinal layers (fig. 325B). On the other hand, the myocardium or muscle tissue of the heart is an association of layers or sheets which tend to be wound in complex spirals. Particularly is this true of the ventricular portion of the heart (fig. 326A). Also, in the stomach, the arrangement of the muscle layers is complex, being composed of an outer longitudinal layer, a middle circular layer, and an inner, somewhat spirally arranged, oblique layer (fig. 326B), The general pattern of arrangement of smooth and cardiac muscle tissues shows much similarity throughout the vertebrate group.

2. Musculature of the Skeleton

The skeletal musculature is striated and under voluntary control. It is that musculature which moves various parts of the endoskeleton and integumental structures, enabling the animal to adapt itself to surrounding environmental conditions. The development of skeletal musculature will be described under the following headings:

(a) development of trunk and tail muscles,

(b) development of muscles of the head-pharyngeal area,

(c) development of the musculature of the paired appendages, and

(d) development of the panniculus carnosus in Mammalia.

a. Development of Trunk and Tail Muscles

1) Characteristics of Trunk and Tail Muscles in Aquatic and Terrestrial Vertebrates. In endeavoring to understand the development of the trunk and



tail musculature in the vertebrate group as a whole, it is important that one consider the environment in which the various species live, for the trunk and tail musculature is adapted to the general functions of moving the animal in its particular habitat. We may recognize three main environmental adaptations :

(1) natatorial,

(2) terrestrial, and

(3) aerial.

a) Natatorial Adaptations. Animals, adapted to swimming, possess a different arrangement of the musculature of the trunk and tail regions than do terrestrial and aerial forms. A transverse section through the tail of the dogfish, Squalus acanthias, demonstrates that the musculature is arranged around the vertebrae in a definite pattern. A horizontal skeletogenous septum extends outward from either side, dividing the muscles on each side of the vertebra into epaxial and hypaxial groups, and dorsal and ventral septa are present in the middorsal and midventral areas (fig. 326C).

Viewed laterally, the muscles are divided by transverse membranes, the muscle septa, myosepta, or myocommata (figs. 326D; 327A). The position of the myocomma corresponds to the intermyotomic (intersegmented) area observed in Chapter 15. Each myocomma is attached to the vertebral body (really several vertebral bodies). The myotomes (fig. 326D) lie in the segmented position between the myocommata and are attached to the latter. In the tail, both these groups of muscles are attached to the myocommata and the vertebrae, but, farther forward in the trunk, it is the epaxial group which is associated directly with the myocommata and the vertebrae, the hypaxial group being less direct in its contact with the vertebral column. (See fig. 31 IB.) In figure 327B, the myotomes and myosepta (myocommata) have a Z-shaped appearance because of a secondary modification during development.

It is evident, therefore, that in the shark, the skeletal muscles of the trunk and tail exist in the form of segments, each segment being divided into an upper epaxial and lower hypaxial component. This arrangement of the muscles and the attachment of the fibers to the myosepta, and thus through the myoseptum to the vertebra, produces a mechanism exceedingly well adapted to the side-to-side movement of the vertebral column so necessary during natation. The conditions present in the sharks are comparable to those of other fishes, and, in all, the epaxial musculature is exceedingly well developed.

b) Terrestrial Adaptations. In the land-frequenting vertebrates, there is less development of and dependence upon the tail region and the dorsal or epaxial musculature for locomotive purposes. In consequence, the epaxial musculature is segregated on either side of the vertebrae in a dorsal position, while the hypaxial musculature and its derivatives in the bilateral appendages are expanded ventrally. The suppression of epaxial muscle development is carried to an extreme form in the aerial adaptations of the bird. In non



aquatic forms the tail musculature is greatly reduced, and in some forms is almost non-existent.

A consideration of the effect that locomotive habits have upon musculature development may be shown by a brief comparison of the musculature in a water-living amphibian, such as Necturus, and in a land-going adventurer, such as the frog. In Necturus, the dorsal (epaxial) musculature, the primitive M. dorsalis trunci, is more like that of the fish, with the muscle fibers attached to the myocommata (fig. 327C), although, contrary to the piscine condition, the muscle fibers close to the vertebrae are attached directly to the vertebrae, where they form short bundles. In the frog, the attachment of the epaxial musculature to the vertebrae is more extensive. Bundles of muscle fibers, the Mm. intertransversarii, pass between the vertebral transverse processes, while Mm. intemeurales connect the transverse processes and spinous processes, respectively, of the vertebrae. A separate muscle, the M. longissimus dorsi, extending from the head to the urostyle, separates from the above-mentioned dorsal muscles (fig. 327D). Although a slight suggestion of myocommata may be present, there is little functional relationship of the myocommata to the vertebrae. Laterally, Mm. coccygeo-sacralis and coccygeo-iliacus also are present as differentiations of the dorsal musculature (fig. 327D). Therefore, a definite formation of special and individual muscles occurs in the dorsal or epaxial musculature of the frog, whereas in Necturus, the dorsal musculature tends to resemble the segmental myotomic condition of the fish. It is to be observed that the dorsal musculature of the frog is adapted to a land-going existence, while the dorsal musculature of Necturus is suited to swimming movements.

A further land adaptation is shown in many salamanders, such as the various species of Desmognathus, where the dorsal trunk musculature differentiates in the neck region into several muscles which insert upon the skull. The latter muscles permit lateral movements of the head.

Turning to the hypaxial musculature, we find that this musculature in Necturus also approaches the condition in fishes. Let us examine this musculature in more detail. In the midventral abdominal area, the fibers assume a primitive, strictly segmental, antero-posterior direction. These muscle bundles form the M. rectus abdominis. Along the lateral side of the body wall, the myosepta (myocommata) are retained between the segmented muscles. However, two layers of muscle fibers are present, an outer thick M. obliquus externus, whose fibers run postero-ventrally, and an inner thin layer, the M. obliquus internus, with fibers coursing antero-ventrally. Turning now to the frog, we find that a segmented rectus abdominis (M. rectus abdominis) is present. In each lateral body wall, an outer external oblique muscle (M. obliquus externus superficialis) runs postero-ventrally, while an internal transverse muscle (M. transversus) courses antero-ventrally (fig. 327D). In Necturus and the frog, therefore, the primitive myotomic condition of the



hypaxial musculature of the shark is disrupted, and the myotomes tend to split into layers or sheets of muscles. This splitting is slight in Necturus and marked in the frog. Also, in the frog, the myocommata are displaced as a part of the muscular-skeletal mechanism, with the exception of the rectus abdominis muscle whose segmentation possibly is a secondary development.

In mammals (fig. 327E), the epaxial musculature is differentiated into a complex of muscles, extending from the sacral area anteriorly into the cervical region and connecting the various vertebrae with each other and the vertebral column with the ribs. The epaxial musculature in the trunk area of the bird is much less developed than it is in the mammal. The hypaxial musculature in both bird and mammal becomes separated into distinct layers, sueh as the external, internal oblique, and transversus muscles. External and internal intercostal muscles are present between the ribs. In the midventral area, the rectus abdominis muscle tends to retain its primitive segmentation.

It is noteworthy to observe that the external and internal intercostal muscles in the mammal appear much the same as the lateral body muscles in Necturus, particularly if we keep in mind the fact that ribs grow out into the myoseptal (myocommal) area (fig. 326D). The external intercostal muscles run posteroventrally, While the internal intercostals pass antero-ventrally from one rib to the next (fig. 327E). The intercostal musculature of the mammal thus retains the primitive, segmented condition.

c) Aerial Adaptations. The musculature of the bird is a highly differentiated organization of structures in which the primitive myotomic plan is greatly distorted. The epaxial musculature is reduced greatly over the trunk region, although well developed in the cervical area. Hypaxial musculature is present in the form of external and internal oblique, and transverse muscle layers. Very short rectus abdominis muscles arc to be found. Aside from the intrinsic muscles of the limbs, a large percentage of the volume of the hypaxial

Fig. 327. Development of branchial and somitic muscles in various vertebrates. (A) Basic areas of the embryo from which skeletal muscle develops. The skeletal muscles of the limb buds are portrayed as masses of mesenchyme represented in this figure as stippled areas in the two limb buds. The origin of this mesenchyme varies in different vertebrates (see text). (B) Skeletal muscular development in the shark. The muscle tissue derived from the hyoid visceral arch is shown in black with white lines. Muscle tissue derivatives from the mandibular visceral arch are shown anterior to the black-white line areas of the hyoid musculature. (C) Same for Necturus maculosus. (D) Same for the frog. (E) Epaxial muscles and intercostal part of hypaxial muscles of cat. External intercostals mostly removed. The “masseter muscle,” a derivative of the mandibular visceral arch tissue of the embryo, also is shown. (F/) Superficial facial and platysma muscle distribution in the cat. These muscles are derivatives of the hyoid visceral and mesenchyme. (E") External pterygoid muscle in the cat, another derivative of the branchial arch mesenchyme. (F) Anterior muscles of- the goose. The muscles derived from the primitive hyoid visceral arch are shown in black with white lines. (Adapted from Huber, 1930. Quart. Rev. Biol., vol. 5, and from Furbringer, 1888, Morphologie und Systematik der Vogel, van Holkema, Amsterdam.) (F') The temporal and masseter muscles in the common fowl. These muscles are derived from the mandibular visceral arch.

Fig. 327 . (See facing page for legend.)




musculature of the bird is contained within the pectoral muscles (fig. 327F). As such the pectoral musculature represents an extreme adaptation to the flying habit. A somewhat similar adaptation is found among mammals, in the bat group, Myotomic metamerism is much less evident in the bird than in any other group of vertebrates, and the only remains of it appear in the intercostal muscles and some of the deeper muscles of the cervical area.

2) Development of Trunk and Tail Musculature: a) General Features OF Myotomic Differentiation in the Trunk. The muscles of the trunk are derived from the primitive myotomes. As described previously, Chapters 11, 12, and 15, the primitive body segment or somite differentiates into the










41/2 WEEKS

Fig. 328. Muscle development in the human embryo. (A and B redrawn from Bardeen and Lewis, 1901, Am. J. Anat., 1.) (A) Early division of truncal myotomes into dorsal

^enaxial) and ventral (hypaxial) regions.
















Fig. 328 — (Continued) Muscle development in the human embryo. (A and B redrawn from Bardeen and Lewis, 1901, Am. J. Anat., 1.) (B) Differentiation of myotomal

derivatives in 11-mm. embryo. Observe that the dorsal division of the spinal nerves is distributed to the epaxial musculature, while the lateral division of the ventral rami passes to the intercostal areas.

sclerotome, myotome, and ’dermatome (fig. 252). After the sclerotome has departed toward the median plane, the myotome and dermatome reconstruct the dermo-myotome which has a myocoelic cavity within (fig. 311 A). The inner layer or myotome gives origin to the muscle fibers of the later myotome. The fate of the dermatome or cutis plate is not definite in all vertebrates. In lower vertebrates it is probable that most of the dermatome gives origin to dermal mesenchyme (Chap. 12). However, in mammals, according to Bardeen (’00) in his studies relative to the pig and human, the dermatome or cutis plate gives origin to muscle cells. On the other hand, Williams (’10) does



not tolerate this view, but believes, in the chick at least, that the dermatome gives origin to dermal mesenchyme.

The primitive position of the myotome is lateral to the nerve cord and notochord. As development progresses, the individual myotomes grow ventrally toward the midventral line (fig. 327A). As this downgrowth progresses, each myotome becomes separated into dorsal (epaxial) and ventral (hypaxial) segments (fig. 328A). As indicated above and in figure 326D, the ribs grow













RECTUS ABDOMINIS sacrospinalis









Fig. 329. Later development of nuisculature in human embryo. (A after Bardeen and Lewis, 1901, Am. J. Anat., 1.) (A) Limb and superficial trunk musculature of 20-mm.

human embryo.
















Fig. 329 — (Continued) Later development of musculature in human embryo. (B after Lewis, 1902, Am. J. Anat., 1.) (B) Developing forelimb musculature of human embryo

(lateral aspect of limb). (C) Differentiation of cloacal musculature in human embryo.




out in the area occupied by the myocommata or connective tissue partitions between the myotomes, and thus ribs and myocommata are correlated intimately with myotomic differentiations in all lower vertebrates. However, in reptiles, birds, and mammals, the outgrowing ribs travel downward within the connective tissue between the myotomes, but the development of the mycommata are suppressed.

b) Differentiation of the Myotomes in Fishes and Amphibia. In the fishes, as the ventral myotomic progression occurs, the differentiating muscle fibers become united anteriorly and posteriorly to the myocommata. In Necturus and in amphibian larvae, in general, this relationship also is established, but, in addition, the myotomes become separated into sheets or layers. In the frog during metamorphosis, this splitting of myotomes and the segregation of separate layers and bundles of distinct muscles is carried further. Also in the frog, a marked migration of separate bundles of muscle fibers occurs, while the fusion of parts of separate myotomes is indicated in the development of the M. longissimus dorsi which superficially appears to be segmented (fig. 327D). There is a pronounced tendency, therefore, in the development of the frog musculature for the primitive myotomic plan to be distorted and myotomes fuse, split, degenerate or migrate to serve the required functional purpose of the various muscles.

c) Differentiation of the Truncal Myotomes in Higher VerteBRATA AND PARTICULARLY IN THE HuMAN Embryo. The principles of myotomic modification by fusion, splitting into separate components, migration of parts of myotomes away from the primitive position, and degeneration of myotomic structure as exemplified in the developing musculature of the frog, are utilized to great advantage in reptiles, birds and mammals. The end to be served in all instances is the adaptation of a particular muscle or muscles to a definite function.

In the development of the adult form of the musculature in the human embryo, the basic division of the primitive myotomes into dorsal (epaxial) and ventral (hypaxial) regions occurs (fig. 328A). The dorsal region of the myotomes is located alongside the developing vertebrae, dorsal to the transverse processes. The ventral portions of the myotomes pass ventrally external to and between the ribs, enclosing the developing viscera.

In a slightly older embryo, the dorsal or epaxial musculature begins to lose its primitive segmentation, and the myotomes fuse into an elongated myotomic column, extending caudally from the occipital area (fig. 328B). The deeper portions of the myotomes, associated with the developing vertebrae, appear to retain their original segmentation, and the Mm. levatores costarum, interspinales, intertransversarii, and rotatores persist as segmental derivatives of the myotomes. The outer layer of the dorsal or epaxial musculature splits lengthwise into an outer muscle group, the dorsally placed Mm. longissimus dorsi and spinalis dorsi, and a latero- ventral Mm. iliocostalis group (fig.



328B). (See Lewis, W. H., ’10.) Between the above two major groups of muscles derived from the epaxial muscle column are other epaxial derivatives such as the semispinalis and multifidus muscles.

The ventral or hypaxial portions of the myotomes overlying the developing ribs fuse into a continuous mass, while the medial portions of the myotomes lying between the ribs give origin to the Mm. intercostales interni and externi. The ventral ends of the fused myotomes on either side of the midventral line split off longitudinally to form the M. rectus abdominis which becomes an elongated sheet, extending from the anterior pectoral area caudal to the differentiating pelvic girdle. The tendency toward segmentation of the two rectus abdominis muscles probably represents a secondary process in man. Tangential splitting of the fused thoracic and abdominal myotomes and migration of the fibers give origin to the Mm. obliquus abdominis externus, obliquus abdominis internus, transversus abdominis, serratus posterior superior, and serratus posterior inferior.

The deep or subvertebral muscles below the vertebral column in the dorsal area are derived from two sources. The Mm. longus colli and longus capitis arise from the migration of myotomic tissue to the ventral vertebral surfaces in the neck region, whereas the Mm. iliopsoas appear to be derived from the musculature of the hind limb (Lewis, W. H., ’10).

d) Muscles of the Cloacal ai^d Perineal Area. The muscle tissue of the cloaca forms a circle of constricting muscular bands which surround the cloacal opening. These muscular bands are derived from myotomic tissue of the posterior truncal region.

In the higher mammals, the primitive cloacal opening becomes divided during development into anterior urogenital and posterior anal openings, and the cloacal musculature is divided into the musculature associated with the urethra, external genital structures, and the anal sphincter (fig. 329C).

e) Development of the Musculature of the Tail Region. The musculature of the tail arises from the tail-bud mesoderm of the early embryo. This mesenchyme condenses to form myotomic concentrations which later divide into epaxial and hypaxial segments as in the truncal region of the body. These myotomic segments are well developed in all fishes and in the adults of amphibia other than the Anura. In fishes the enlarged condition of the epaxial and hypaxial muscles of the tail region coincides with the elongation of neural spines and hemal processes of the tail vertebrae where they serve the function of moving the caudal fin from side to side. Three main types of caudal fin skeletal arrangement in fishes (see fig. 331B-D) act as the framework for the fin which serves the relatively enormous propulsive force generated by the tail musculature.

In Necturus, in Cryptobranchus, and in other water-dwelling amphibians, and also in crocodilians, whales, etc., the tail musculature is developed to serve the natatorial function which requires a lateral movement of the tail.



On the other hand, the prehensile or grasping movement of the tail of the opossum, or the tails of western-hemisphere monkeys necessitates an extreme adaptation on the part of individual muscle bundles and their attachment to the caudal vertebrae. Similar specializations are found in the writhing tail of the cat group. The wagging movement of the tail of the dog or the swishing motion of the tails of cows, horses and other mammals is the result of the activities of the Mm. abductor caudae internus and abductor caudae externus which appear to be derivatives of the hind-limb musculature.

b. Development of Muscles of the Head-pharyngeal Area

1) Extrinsic Muscles of the Eye. The extrinsic muscles of the eyeball are one of the most constant features of vertebrate morphology. Six muscles for each eye are found in all gnathostomes, innervated by three cranial nerves as follows:

(1) M. rectus superior — cranial nerve III,

(2) M. rectus internus or anterius — cranial nerve 111,

(3) M. rectus inferior — cranial nerve III,

(4) M. rectus externus (posterius or lateralis) — cranial nerve VI,

(5) M. obliquus superior — cranial nerve IV, and

(6) M. obliquus inferior — cranial nerve III.

To these muscles may be added the Mm. retractor oculi of many mammals and the Mm. quadratus and pyramidalis of birds.

In the shark group, the muscles of the eye arise from three pre-otic somites or head cavities, namely, the pre-mandibuiar, mandibular and hyoid somites (figs. 253, 327A). The pre-mandibular somite, innervated by the oculomotorius or third cranial nerve, gives origin to all of the rectus muscles with the exception of the Mm. rectus externus. The Mm. obUquus inferior also arises from the pre-mandibular somite. From the mandibular somite, innervated by the trochlearis or fourth cranial nerve, arises the Mm. obliquus superior, while the hyoid somite gives origin to the Mm. rectus externus (Balfour, 1878; Platt, 1891; Neal, T8). A derivation of eye muscles from three pre-otic somites or mesodermal condensations has been described in the gymnophionan amphibia by Marcus (’09), in the turtle by Johnson (M3), in the chick by Adelmann (’26, ’27), and in the marsupial mammal, Trichosurus, by Fraser (’15). For extensive references regarding the eye-forming somites or mesodermal condensations, see Adelmann (’26, and ’27).

Various disagreements, concerning the presence or absence of the various head somites and the origin of the eye muscles therefrom, are to be found in the literature. Regardless of this lack of uniformity of agreement, it is highly probable that the premuscle masses of tissue which give origin to the eye muscles in the gnathostomous vertebrates, in general, adhere closely to



the pattern of the eye-muscle development from three pre-otic pairs of somites as manifested in the shark embryo.

2) Muscles of the Visceral Skeleton and Post-branchial area: a) Tongue AND Other Hypobranchial Musculature. As indicated in figures 253 and 3 27 A, a variable number of post-otic or met-otic somites are concerned with the composition of the head of the gnathostomous vertebrate. In the dogfish, Squalus acanthias, about six pairs of post-otic somites contribute to the structure of the head ( De Beer, ’22). For most vertebrates, about three pairs of post-otic somites, a conservative estimate, appear to enter into the head’s composition. The hypobranchial musculature in the elasmobranch embryo arises as myotomal buds from the myotomes of posterior head area. These muscle buds migrate ventrad from these myotomes to the hypobranchial region as indicated in figure 253. Associated with this migration of myotomal material is the migration and distribution of the hypoglossal nerve, compounded from the ventral roots of post-otic spinal nerves to this area (fig. 253). In the human, W. H. Lewis (’10) favors the view that the tongue musculature arises in situ from the hypobranchial mesenchyme, but Kingsbury (’15) suggests the post-otic origin of the tongue musculature for all vertebrates. Regardless of its origin, the tongue musculature is innervated by ventral nerve roots of post-otic segments in higher vertebrates, i.e., the hypoglossal or twelfth cranial nerve. The tongue musculature becomes associated with the basihyal portion of the hyoid arch, which acts as its support. In mammals, the sternohyoid, sternothyroid, and omohyoid muscles are innervated also by the hypoglossal or twelfth cranial nerve. These muscles probably arise from the post-otic myotomes in a manner similar to the tongue musculature.

b) Musculature of the Mandibular Visceral Arch. The mesoderm, associated with this arch, gives origin to the muscles of mastication, and as a result these muscles are innervated by special visceral motor fibers located in the trigeminal or fifth cranial nerve. In the shark, the muscles arising from the mandibular visceral arch tissue are the adductor mandibulae and the first ventral constrictor muscles (fig. 327B); in the frog, the temporal, masseter, pterygoid, and mylohyoid muscles; in the chick, the pterygotemporal, temporal, and digastric muscles; and, in mammals, the temporal, masseter, pterygoid, anterior portion of the digastric, mylohoid, tensor tympani, and tensor veli palatini muscles (fig. 327D, E', E", F, F').

c) Musculature of the Hyoid Visceral Arch. The musculature, which develops from mesenchyme associated with the embryonic hyoid arch, becomes distributed as indicated in figures 327 and 330. It is to be observed that, in the adult shark (fig. 327B), this musculature functions in relation to the hyoid arch. In the adult frog (fig. 327D), it is represented by deep facial musculature or the depressor mandibulae and subhyoideus muscles. In the adult goose (fig. 327F), it is present as the M. sphincter colli, which



represents superficial facial musculature, and the M. depressor mandibulae or deep facial musculature. In mammals (figs. 327E'; 330A-D), the muscles derived from the hyoid arch is distributed over the cervico-facial area as many separate muscles. The musculature derived from the hyoid arch is innervated by the seventh or facial cranial nerve. Reference may be made to the extensive review of the literature by Huber (’30, a and b), relative to the facial musculature in vertebrates.

d) Musculature of the First Branchial Arch. The musculature of the first branchial arch is innervated by the glossopharyngeal or ninth cranial nerve. In the shark, the muscle tissue arising from the first branchial arch becomes the constrictor musculature of this arch, but, in the mammal, it gives origin to the stylopharyngeus muscle and to the constrictors of the pharynx.

e) Muscles of the Succeeding Visceral Arches. In the shark, these muscles contribute to the constrictor muscles of the gill arches and are under the domain of the vagus or tenth cranial nerve. In the mammal, this muscle tissue becomes associated with the larynx and with the constrictors of the


f) Muscles Associated with the Spinal Accessory or Eleventh Cranial Nerve. The sternocleidomastoid and trapezius musculature in the human, according to W. H. Lewis (TO), arises from a premuscle mass associated at the caudal end of the pharyngeal area below the post-otic myotomes (fig. 336A). With the musculature arising from this premuscle mass, the spinal accessory or eleventh cranial nerve becomes associated. The trapezius musculature migrates extensively over the scapular area (fig. 329A).

g) Musculature of the Mammalian Diaphragm. The striated musculature of the mammalian diaphragm appears to arise from the ventral portions of the myotomes in the midcervical area. In the human, this diaphragmatic musculature is innervated by the ventral roots of cervical nerves IV and V, while, in the cat, cervical nerves V and VI are involved. These ventral rami give origin to the phrenic nerve, which later migrates posteriad with the diaphragmatic musculature together with the developing diaphragm during the division of the coelomic cavities (Chap. 20).

c. Development of the Musculature of the Paired Appendages

Two main theories have arisen relative to the origin of the paired appendages. One is the gill-arch theory of Gegenbauer (1876) and the fin-fold or lateral-fold theory of Balfour ( 1881 ). According to the theory of Gegenbauer, the limb girdles are modified gill arches, and the limb tissue itself represents a modification of the gill septa and supporting gill rays. The pelvic limbs were produced, according to this theory, by a backward migration of the gill arch involved. The lateral-fold theory, on the other hand, postulated that the paired limbs were derived from longitudinal fin folds. The endoskeleton within the






Fig. 330. Facial and cervical muscles in mammals derived from the mesoderm of the hyoid arch. (Redrawn from Huber, 1930, Quart. Rev. Biol., 5.) (A) Opossum (Didel phys). (B) Cat (Felis). (C) New-born baby (white) human. (D) Adult (white) human.

fold arose as a support for the fold in a manner similar to the median fins. The latter theory has the greatest number of adherents today.

The early development of the rudiments of the paired appendages and the properties of the limb field are discussed in Chapter 10, page 508. Relative to the developing limb, the exact origin of the cells which go to make up its intrinsic musculature has been the object of much study. In the elasmobranch and teleost fishes, muscle buds from the myotomes in the vicinity of the developing fin fold unquestionably contribute dorsal and ventral premuscle masses of cells to the limb, which give origin respectively to

1 ) the dorsal, elevator and extensor muscles, and

2) the ventral depressor and adductor muscles of the fin.



In tetrapod vertebrates, however, the exact origin of the cells which enter into the formation of the limb’s intrinsic musculature is open to question. In the amphibia, including Vrodela and Anura, Field (1894) described myotomic processes which contribute to the musculature of the anterior limbs. Byrnes (1898), working experimentally with the same group, and W. H. Lewis (’10b) deny this conclusion and affirm the somatopleural or in situ

Fig. 331. (A) Innervation of premuscie masses in head and pharyngeal areas, and of myotomes in the cervical and caudal head regions of 7-mm. human embryos. Four post-otic (occipital) myotomes and the premuscle mass of the trapezius and sternomastoid muscles are shown just back of the tenth cranial nerve. The first cervical myotome and spinal nerve are shown just posterior to the fourth occipital myotome. (Redrawn from W. H. Lewis, 1910, chap. 12 in Manual of Human Embryology, vol. 1, by F. Keibel and F. P. Mall, Philadelphia, Lippincott.) (B, C, D) Types of caudal fins in fishes.



origin of the limb musculature and connective tissues. Similar affirmations and denials are found in the literature, relative to origin of the intrinsic limb muscles in higher vertebrates, including man. For example, Ingalls (’07) described myotomic cell migrations into the developing human limb, whereas W. H. Lewis (’10a) was not able to subscribe to this view.

Although actual muscle tissue from the myotomes to the limb buds cannot be traced in all cases, the fact remains that the nerve supply to a myotome or to a particular group of muscle-forming cells appears to be a constant feature. For example, the facial musculature, which is derived from the hyoid arch mesenchyme of the embryo as set forth above, retains its innervation by the facial or seventh cranial nerve, even though the muscle migrates far forward from its original site of development. The innervation of the trapezius muscle by the spinal accessory nerve is another example of this same fidelity of the nerve supply to the original site of the origin of the muscle-forming cells. Mall (1898, p. 348) describes this relationship between the nerves and myotomes as follows: “As the segmental nerves appear, each is immediately connected with its corresponding myotome, and all of the muscles arising from a myotome are always innervated by branches of the nerve which originally belonged to it.” (See fig. 331 A.)

The development of the musculature of the tetrapod limb involves two main premuscle masses of tissue:

( 1 ) An intrinsic mass of muscle-forming mesenchyme within the developing limb which condenses to form separate muscle-forming associations of cells around the developing skeleton of the limb. Each of these cellular associations then proceeds to differentiate into a particular muscle or closely integrated group of muscles (figs. 328B; 329 A and B). That is, the intrinsic mass of muscle-forming tissue gives origin to the intrinsic musculature of the limb.

(2) An extrinsic mass of premuscle tissue which ultimately gives origin to the musculature which attaches the limb and its girdle to the axial skeleton. This premusclc tissue arises from two sources:

(a) Premuscle tissue from the limb bud which migrates from the limb bud proximally toward the axial skeleton. In the forelimb, the pectoral, latissimus dorsi, and teres major muscles develop from this mass of tissue, while in the hind-limb the caudo-femoralis, iliopsoas, piriformis, and certain of the gluteal muscles appear to arise from muscle -forming tissue which extends axially to unite the limb with the axial skeleton.

(b) Premuscle tissue which arises outside the limb bud mesenchyme. The muscles which arise from this tissue serve to attach the limb girdle to the axial skeleton. From premuscle tissue of this type arise the Mm. trapezius, sternocleidomastoideus, rhomboidei, levator scapulae, serratus anterior, and omohyoideus.



d. Fannie ulus Carnosus

There are two groups of skeletal “skin muscles,” that is, muscles under voluntary control which move the skin and skin structures. One group is the mimetic or facial musculature, described on page 717 and originating from the primitive hyoid mesoderm; the other is the panniculus carnosus, found only in the Mammalia and derived embryologically from the tissue which forms the pectoral musculature. The facial musculature is innervated by cranial nerve VII or the facial nerve, while the panniculus carnosus receives its innervation from the anterior thoracic nerves (fig. 327E').

The panniculus carnosus is highly developed in the guinea pig and porcupine and, although less developed in the rabbit, cat, dog, and horse, it forms a prominent muscular layer. The fibers may be divided into two groups:

(a) fibers which arise and insert in the superficial fascia of the skin and

(b) fibers that arise in the superficial fascia of the back and thigh and converge toward the greater tuberosity of the humerus, where they insert.

For extensive references and descriptions, see Langworthy (’24 and ’25).


Adelmann, H. B. 1926. The development of the premandibular head cavities and the relations of the anterior end of the notochord in the chick and robin. I. Morphol. 42:371.

. 1927. The development of the

eye muscles of the chick. J. Morphol. 44:29.

Balfour, F. M. 1878. A monograph on the development of elasmobranch fishes. Chap. X in The Works of Francis Maitland Balfour. Edited by M. Foster and A. Sedgwick. Vol. 1, 1885. Macmillan and Co., London.

. 1881. On the development of the

skeleton of the paired fins of elasmobranchii, considered in relation to its bearings on the nature of the limbs of the Vertebrata. Chap. XX in The Works of Francis Maitland Balfour. Edited by M. Foster and A. Sedgwick. Vol. 1, 1885. Macmillan and Co., London.

Bardeen, C. R. 1900. The development of the musculature of the body wall in the pig. Johns Hopkins Hospital Reports. 9:367.

Byrnes, E. F, 1898. Experimental studies on the development of limb-muscles in Amphibia. J. Morphol. 14:105.

De Beer, G. R. 1922. The segmentation of the head in Squalus acanthius. Quart. J. Micr. Sc. 66:457.

Field, H. H. 1894. Die Vornierenkapsel, ventrale Musculatur und Extremitatenanlagen bei den Amphibien. Anat. Anz. 9:713.

Fraser, E. A. 1915. The head cavities and development of the eye muscles in Trichosurus vulpecula with notes on some other marsupials. Pr6c. Zool. Soc., London, sA. 299.

Gegenbaur, C. 1876. Zur morphologie der Gliedmaassen der Wirbelthiere. Morph. Jahrb. 2:396.

Huber, E. 1930a. Evolution of facial musculature and cutaneous field of Trigeminus. Part I. Quart. Rev. Biol. 5:133.

. 1930b. Evolution of facial musculature and cutaneous field of Trigeminus. Part 1. Quart. Rev. Biol. 5:389.

Ingalls, N. W. 1907. Beschreibung eincs menschlichen Embryos von 4:9mm. Arch. f. mikr. Anat. u. Entwicklngsgesch. 70:506.



Johnson, C. E. 1913. The development of the prootic head somites and eye muscles in Chelydra serpentina. Am. J. Anat. 14:119.

Kingsbury, B. F. 1915. The development of the human pharynx. Part 1. The pharyngeal derivatives. Am. J. Anat. 18:329.

Langworthy, O. R. 1924. The panniculus carnosus in cat and dog and its genetical relationship to the pectoral musculature. J. Mammalogy. 5:49.

. 1925. A morphological study of

the panniculus carnosus and its genetical relationship to the pectoral musculature in rodents. Am. J. Anat. 35:283.

Lewis, M. R. 1919. The development of cross-striations in the heart muscle of the chick embryo. Johns Hopkins Hosp. Rep. 30:176.

Lewis, W. H. 1910a. Chap. 12, Development of the Muscular System in Human Embryology. Edited by Keibel and Mall. J. B. Lippincott Co., Philadelphia.

. 1910b. The relation of the myo tomes to the ventrolateral musculature and to the anterior limbs in Amblystoma. Anat. Rec. 4: 183.

. 1922. The adhesive quality of

cells. Anat. Rec. 23:387.

Mall, F. P. 1898. Development of the ventral abdominal walls in man. J. Morphol. 14:347.

Marcus, H. 1909. Beitrage zur Kenntnis der Gymnophionen. III. Zur Entwicklungsgeschichte des Kopfes, I Teil. Morph. Jahrb. 40:105.

Neal, H. V. 1918. The history of the eye muscles. J. Morphol. 30:433.

Patten, B. M. and Kramer, T. C. 1933. The initiation of contraction in the embryonic chick heart. Am. J. Anat. 53:349.

Platt, J. B. 1891, A contribution to the morphology of the vertebrate head, based on a study of Acanthias vulgaris. J. Morphol. 5:79.

Williams, L. W. 1910. The somites of the chick. Am. J. Anat. 11:55.


Tke Circulatory System

A. Introduction

1. Definition

2. Major subdivisions of the circulatory system

B. Development of the basic features of the arteriovenous system

1. The basic plan of the arteriovenous system

2. Development of the primitive heart and blood vessels associated with the primitive gut

3. Formation of the primitive blood vessels associated with the mesodermal and neural areas

4. Regions of the primitive vascular system

C. Histogenesis of the circulatory system

1. The heart

2. Formation of the primitive vascular channels and capillaries

3. Later development of blood vessels

a. Arteries

b. Veins

c. Capillaries

4. Hematopoiesis (Hemopoiesis)

a. Theories of blood-cell origin

b. Places of blood-cell origin

1 ) Early embryonic origin of blood cells

2) Later sites of blood-cell formation

3) Characteristics of development of the erythrocyte

4) Characteristics of various white blood cells

a) Granulocytes

b) Lymphoid forms

D. Morphogenesis of the circulatory system

1. Introduction

2. Transformation of the converging veins of the early embryonic heart into the major veins which enter the adult form of the heart

a. Alteration of the primitive converging veins of the heart in the shark, Squalus acanthids

b. Changes in the primitive converging veins of the heart in the anuran amphibia

1) The vitelline veins

2) Lateral (ventral abdominal) veins

3) Formation of the inferior vena cava

4) Formation of the renal portal system

5) Precaval veins




c. Changes in the primitive converging veins of the heart in the chick

1) Transformation of the vitelline and allantoic veins

a) Vitelline veins

b) Allantoic veins

2) Formation of the inferior vena cava

3) Development of the precaval veins

d. The developing converging veins of the mammalian heart

3. Development of the heart

a. General morphology of the primitive heart

b. The basic histological structure of the primitive embryonic heart

c. Importance of the septum transvcrsum to the early heart

d. Activities of early-heart development common to all vertebrates

e. Development of the heart in various vertebrates

1 ) Shark, Squaliis acanthias

2) Frog, Rana pipiens

3 ) Amniota

a) Heart of the chick

b) Mammalian heart

( 1 ) Early features

(2) Internal partitioning

(3) Fate of the sinus venosus

(4) The division of the bulbus cordis (truncus arteriosus and conus)

f. Fate of embryonic heart segments in various vertebrates

4. Modifications of the aortal arches

5. Dorsal aortae (aorta) and branches

E. Development of the Lymphatic System

F. Modifications of the circulatory system in the mammalian fetus at birth

G. The initiation of the heart beat

A. Introduction

1. Definition

Living matter in its active state depends for its existence upon the beneficent flow of fluid materials through its substance. This passage of materials consists of two phases:

( 1 ) the inflow of fluid, containing food materials and oxygen, and

(2) the outflow of fluid, laden with waste products.

In the vertebrate group as a whole, the inflow of materials to the body substance occurs through the epithelial membranes of the digestive, integumentary, and respiratory systems, while the outflow of materials is effected through the epithelial membranes of the excretory, respiratory, and skin surfaces. The passage of materials through the substance of the body lying between these two sets of epithelial membranes is made possible by (a) the blood and (b) a system of blood-conveying tubes or vessels. These structures form the circulatory system.



2. Major Subdivisions of the Circulatory System

The circulatory system is composed of two major subdivisions:

( 1 ) the arteriovenous system, composed of the heart, arteries, and veins together with the blood vessels and capillaries of smaller dimensions intervening between the arteries and veins, and

(2) the lymphatic system, made up of lymph sacs, and lymphatic vessels together with specialized organs such as the spleen, tonsils, thymus gland, and lymph nodes. In larval and adult amphibia pulsating lymph hearts are a part of the lymphatic system. Lymph hearts are present also in the tail region of the chick embryo.

The lymphatic vessels parallel the vessels of the arteriovenous system, and one of their main functions appears to be to drain fluid from the small spaces within tissues as well as larger spaces, such as the various divisions of the coelomic cavity.

The blood within the arteriovenous system is composed of a fluid substance or plasma together with red blood corpuscles or erythrocytes, white blood cells of various types, and blood platelets. The latter are small protoplasmic bodies which may represent cytoplasmic fragments of the giant, bone-marrow cells or megakaryocytes. The blood within the lymphatic system is composed of a vehicle the lymph fluid, similar to the plasma of the arteriovenous blood system, together with various white blood corpuscles.

B. Development of the Basic Features of the Arteriovenous System

1, The Basic Plan of the Arteriovenous System

The primitive circulatory system is constructed of three main parts:

( 1 ) two sets of simple capillary tubes, bilaterally developed on either side of the median line (fig. 332),

(2) a local modification of these tubes which forms the rudimentary heart, and

(3) blood cells and fluid contained within the tubes.

2. Development of the Primitive Heart and Blood Vessels Associated with the Primitive Gut

The primitive vascular tubes or capillaries form below the anterior region of the developing metenteron or gut tube in relation to the yolk sac or yolkcontaining segment of the gut. Two sets of identical tubes begin to form, one set on either side of the median plane of the embryo (fig. 3 32 A and B). Simultaneous with the formation of these primitive, subintestinal blood capillaries, the splanchnic layers of the two hypomeric portions of the mesodermal tubes grow mesiad to cup around the blood capillaries in the area just posterior


to the forming pharyngeal area of the gut tube (figs. 234; 236D, E; 332F-M). This encirclement of the primitive blood capillaries by the splanchnic layers of the hypomeric mesoderm produces the rudimentary tubular heart, composed within of two fused subintestinal capillaries and without of modified fused portions of the hypomeric mesoderm. The modified portions of the hypomeric mesoderm form the epimyocardial rudiment of the heart, while the fused capillaries within establish the rudimentary endocardium (fig. 332F-M).

Proceeding anteriad from the area of primitive tubular heart, the blood capillaries establish the primitive ventral aortae (fig. 332A).

From the primitive ventral aortae, the two capillaries move forward toward the anterior end of the foregut where they diverge and pass dorsally, one on either side of the foregut, as the first or mandibular pair of aortal arches. In the dorsal area of the foregut the two primitive aortal arches pass inward toward the median plane and each aortal arch joins a primitive capillary which runs antero-posteriorly along the upper aspect of the developing gut tube. These two supraintestinal blood vessels are the rudiments of the future dorsal aorta and they are known as the dorsal aortae. They lie above the primitive gut and below the notochord. In the region where the mandibular pair of aortal arches joins the dorsal aortae, each primitive dorsal aorta sends a capillary sprout toward the developing eye region and the brain. This capillary forms the rudiment of the anterior end of the internal carotid artery. About the midregion of the developing midgut, each of the dorsal aortae sends off a lateral branch which connects with a series of capillaries in the yolk or yolk-sac area of the deveoping midgut. The vessels which diverge from the dorsal aorta to the yolk-sac region form the rudiments of the two vitelline arteries. The capillary network in the yolk region or yolk-sac area of the midgut in turn connect with the two subintestinal capillaries, previously mentioned, which enter the forming heart. The two latter blood vessels constitute the vitelline veins (fig. 332B). Meanwhile, successive pairs of aortal arches are formed posterior to the first pair, connecting the ventral aortae with the dorsal aortae (fig. 332D). These aortal arches pass through the substance of the visceral arches, as mentioned in Chapters 14 and 15.

3. Formation of the Primitive Blood Vessels Associated WITH the Mesodermal and Neural Areas

The system of blood vessels described above (fig. 232A) is developed in relation to the primitive gut tube. Very shortly, however, another system of vessels is established dorso-laterally to the mesodermal tubes. This second system of blood capillaries forms the beginning of the cardinal system (fig. 232B). The cardinal system is composed of two anterior cardinal veins which begin as a series of small capillaries on either side over the forming brain; from whence these veins proceed backward, one on either side over the branchial mesoderm, and lateral to the forming somites. These vessels



eventually proceed latero-ventrad in their development along the outer lateral aspect of the somatopleural mesoderm to the caudal regions of the forming heart, where they turn ventrad along the outer aspect of the somatopleural layer of the hypomere. In the region where the anterior cardinal veins turn ventrad toward the heart region, each anterior cardinal vein is joined by a posterior cardinal vein. The latter proceeds forward from the posterior end of the developing embryo, lying along the outer aspect of the nephrotomic portion of the hypomere below the primitive epidermal tube (fig. 332B). The union of the anterior and posterior cardinal veins on either side forms the common cardinal vein. The latter travels postero-ventrally along the outer aspect of the somatopleure until it reaches the upper limits of the caudal region or sinus venosus of the developing heart. In this area, the splanchnopleural layer (epimyocardium) and the endocardial layer of the developing sinus venosus, bulge laterad to fuse with the somatopleural layer of the hypomere. This area of contact between the epimyocardial layer of the sinus venosus and somatopleural mesoderm produces a bridge across the coelomic space. The two posterior, dorso-lateral regions of the sinus venosus thus extend dorso-laterad on either side across the coelomic space to join the somatopleure. Each common cardinal vein perforates through the somatopleure in this area and empties into the sinus venosus at a point lateral to the entry of the two vitelline veins (fig. 332C). This bridge established across the coelomic cavity from the somatopleure of the body wall to the splanchnopleure of the heart forms a lateral mesocardium on either side. The two lateral mesocardia

Fig. 332. Early development of primitive vascular system including tubular heart. (The diagrams included in this figure should be studied together with descriptions in Chapter 10 relative to tubulation of the major organ-forming areas of the early embryo.) (A) Diagram of the early bilaterally developed vascular tubes (capillaries) which form in relation to the primitive gut tube. This system of capillaries constitutes the first or early vitelline system of developing circulatory structures. (B) The cardinal or primary venous system is added to the primitive vitelline system. (C) The area of union between the early vitelline and cardinal systems at the caudal end of the heart. (D) The basic (fundamental) condition of the vascular system. (E) Two diagrams showing the union of the vitelline and cardinal systems distally between the somites and near the nerve cord. The three vascular tubules to the left in this drawing show an early relationship of the intersegmental arteries and veins, and the drawing of the three vascular tubules to the right depict a later stage of this developmental relationship. (F-M) Stages in the development of the early tubular heart in shark, frog, and chick embryos. As the mammal is similar to the chick it is not included. (F~H) Early development of the heart in Squalus acanthias. (F) The lower, mesial edges of the hypomeric mesoderm begins to cup around the primitive subintestinal capillaries. (G) Later stage. (H) A transverse section through the heart which is now in the form of a straight tube comparable to that shown in Fig. 3 39 A. (I-K) Early stages in the development of the frog heart. Observe that the ventral areas of the two hypomeres become confluent and later form a trough-like cup around the forming subintestinal capillaries below the foregut. (Redrawn from Kellicott, 1913. Outlines of Chordate Development, Henry Holt, N. Y.) (L-M)

Early development of the chick heart. (L) At about 26 hrs. of incubation. (M) About 30 hrs. of incubation.


internal carotid

Fig. 332. (See facing page for legend.)




represent the initial stages in the development of the various coelomic divisions of the primitive coelomic space (Chap. 20).

As the cardinal and intestinal systems of the primitive vascular system become joined together centrally via the common cardinal veins, the two systems become joined peripherally by means of a series of intersegmental blood vessels. The latter arise from the dorsal aortae and travel dorsally between the somites and myotomes to the central nerve tube (fig. 232E). In the nerve-tube area, the primitive intersegmental arteries become continuous with the rudiments of the intersegmental veins which course laterad to join the anterior and posterior cardinal veins. When the above vascular channels are well established, another set of veins is formed between the somatopleural mesoderm of the hypomere and the developing integument (figs. 332D; 336C, D). The last veins course along the lateral body wall, arising in the pelvic area and emptying into the sinus venosus of the heart. In fishes and amphibia, these veins are called lateral veins, but in reptiles, birds, and mammals, they are denominated the allantoic or umbilical veins as they drain principally the allantoic area of the embryo.

4. Regions of the Primitive Vascular System

The primitive morphological plan of the vascular system, as outlined above, is a basic condition strikingly comparable in all vertebrate embryos. In view of the later changes of this fundamental vascular plan necessitated by the adaptation of the vascular system to the environmental conditions existing within the various habitats of the adult, it is well to demarcate, for the purposes of later discussion, certain definite regions of the primitive arteriovenous system. These regions are (fig. 332D):

(1) the converging veins of the heart, composed of the lateral, common cardinal, anterior and posterior cardinal, and vitelline veins,

(2) the primitive heart, made up of the primitive sinus venosus, atrium, ventricle, and bulbus cordis,

(3) the branchial area, composed of the ventral aortae, aortal arches, and adjacent dorsal aortae, and,

(4) the dorsal aortae (later aorta) and efferent branches.

C. Histogenesis of the Circulatory System

1. The Heart

Consult Chap. 16.

2. Formation of the Primitive Vascular Channels and Capillaries

Two principal theories have emerged to account for the origin of the primitive blood vessels in the embryo. These theories are the angioblast theory and the local origin theory.



The angioblast theory rests upon the assumption that a special vascular tissue, called the angioblast by Wilhelm His, develops in the area of the yolk sac. This angioblast tissue, according to the angioblast theory, forms a vascular rudiment within which the endothelium, or flattened epithelial cells peculiar to blood capillaries, is developed. This endothelium produces the primitive capillaries of the yolk area, and, further, it grows into the developing embryo where it forms the endothelium of the entire intra-embryonic vascular system. That is, the angioblast in the yolk area provides the source from which arises the endothelial lining of all the primitive blood vessels of the embryo and also of all later endothelium of later blood vessels. The endothelium of all blood vessels thus traces its ancestry back to the yolk-sac angioblast.

The local origin theory may be divided into two schools of thought. One school espouses the idea that “mesenchyme may, in practically any region of the body, transform into vascular tissue” (McClure, ’21, p. 221). Accordingly, primitive blood capillaries arise in loco from mesenchyme in various parts of the embryo, and these local vessels sprout, grow, and become united to form the continuous vascular system. The endothelium which forms the walls of all capillaries and the lining tissue of all blood vessels of larger dimensions forms directly from mesenchyme. Addition to this mesenchyme may occur by proliferation from endothelium already formed or by the conversion of mesenchyme as single cells or cellular aggregates (McClure, ’21; Reagan, ’17).

A second school which advocates the local origin of blood vessels differs from the view described above principally by the assumption that, while the endothelium of blood vessels appears to arise in loco from the mesenchyme, it is not a generalized type of mesenchyme but rather a “slightly modified mesenchymal cell” (Stockard, ’15). Relative to this position, the following quotation from Stockard, ’15, p. 323, is given:

The facts presented seem to indicate that vascular endothelium, erythrocytes and leucocytes, although all arise from mesenchyme, are really polyphyletic in origin: that is, each has a different mesenchymal anlage. To make the meaning absolutely clear, I consider the origin of the liver and pancreas cells a parallel case. Both arise from endoderm, but each is formed by a distinctly different endodermal anlage, and if one of these two anlagen is destroyed, the other is powerless to replace its product.

3. Later Development of Blood Vessels

While the capillary possessing a wall composed of thin, flattened endothelial cells is the basic or fundamental condition of all blood vessels in the body, it is only of transitory importance in the development of the arteries and veins. For, in the formation of the arteries and the veins, the primitive capillary enlarges and its endothelial wall is soon reinforced by the addition of white and elastic connective tissue fibers and smooth muscle tissue. The



connective tissue and smooth muscle develop from the adjacent mesenchyme present in the area in which the capillary makes its appearance.

a. Arteries

The arteries are the system of blood vessels which convey the blood from the heart to the systemic organs. Most arteries are composed of three coats of tissue which come to surround the endothelium of the capillary, namely, an inner tunica intima, a middle tunica media, and an outer tunica adventitia. The tunica media is composed of smooth muscle fibers and elastic connective tissue fibers, while the other two coatings are fabricated of connective tissue fibers.

In the large arteries in the immediate vicinity of the heart, the tunica media is poorly muscularized but its elastic fibers are plentiful. However, in the more distally placed arteries, the so-called distributing arteries which include most of the arteries, the tunica media is supplied copiously with smooth muscle fibers.

6. Veins

The veins are the vascular tubes which convey the blood from the systemic organs back to the heart. The walls of the veins are more delicate than those of the arteries, and the various tunics mentioned above are thinner, especially the tunica media. The veins of the extremities form internal, pocket-shaped valves which prevent the blood from moving backward.

c. Capillaries

The capillaries which form the ramifying bed of blood vessels between the arteries and veins retain the primitive condition, and their walls are composed of flattened endothelial cells. The size of the arteries and the thickness of the arterial walls decrease as they approach the capillary bed, while those of the veins increase as they leave the capillary area.

4. Hematopoiesis (Hemopoiesis) a. Theories of Blood-cell Origin

Hematopoiesis is the name given to the process which effects the formation of blood cells. Though it is agreed that blood cells generally arise from mesenchymal cells, all students of the problem do not concur in the belief that all arise from a specific type of mesenchymal cell. For example, in the quotation given above from Stockard, T5, it is stated that one type of mesenchymal cell gives origin to the red blood cells, while leukocytes or white blood cells arise from a slightly different type of mesenchymal cell. This may be called the dualistic theory of hematopoiesis. The view held today by many in this field of development is that all blood cells arise from fixed, undif



ferentiated, mesenchymal cells which give origin to a mother cell, the hemocytoblast. From the hemocytoblast, four main stem cells arise, lymphoblasts, monoblasts, granuloblasts, and erythroblasts, each of which differentiates into the adult type of blood cell as shown in fig. 33 3 A. Such an interpretation is the basis for the monophyletic or Unitarian theory of blood cell origin. Some observers, however, believe that the erythrocyte, granulocyte, and the monocyte each have a separate stem cell. The latter view is the basis of the trialistic theory. (Consult Maximow and Bloom, ’42, pp. 107-116 for discussion relative to blood-cell origin.)

b. Places of Blood-cell Origin

1) Early Embryonic Origin of Blood Cells. It long has been recognized that the yolk-sac area is a region of early blood-cell development. This is one aspect of the angioblast theory of His, referred to on page 731. In the teleost fish, Fundidus, Stockard (’15) reports the origin of red blood cells from two main sources:

( 1 ) an intermediate celt mass or blood string in the vicinity of the notochord and

(2) the blood islands in the yolk sac.

However, the yolk-sac area appears to be the primary source for the early phases of hematopoiesis in most vertebrate embryos. In the human embryo, both red and white cells have been described as arising from primitive hemocytoblasts in the yolk sac by Bloom and Bartelmez ('40). These authors report the origin of primitive erythrocytes as arising primarily intra-vascularly, although some develop extra-vascularly. Definitive erythrocytes develop, according to these authors, in the entoderm and within blood vessels of the yolk sac (fig. 333B). In the 24-hr. chick embryo, the blood islands in the area vasculosa of the blastoderm show a direct conversion of mesodermal cells into primitive blood cells and the endothelium of the forming blood capillaries (fig. 333C). In the frog, blood islands appear in the mesoderm and entoderm of the ventro-lateral areas of the body of 3- to 4. 5 -mm. embryos. These islands are extensive, extending from the liver area caudally toward the tail-bud region.

2) Later Sites of Blood-cell Formation. As indicated previously in teleost fishes, early blood formation occurs in the region of the notochord near the developing kidney tissue, as well as in the yolk-sac area. During later development, hematopoiesis in teleost fishes is centered in the kidney area. The origin of blood cells from kidney tissue also is true in the amphibian tadpole (Jordan and Speidel, ’23, a and b). The liver also functions in these forms to produce blood cells. In the developing shark embryo, blood cells appear to be formed around the heart and later in the esophageal area of the adult. In the adult frog, the spleen functions as a center of blood-cell formation, although in the



Fig. 333. Developing blood cells. (A) Diagram showing origin of different types of blood cells from the primitive hemocytoblast. (Redrawn and slightly modified from Patten, 1946. Human Embryology, Blakiston, Philadelphia.) (B) Blood-cell origin in the yolk-sac area of human embryo. (Redrawn from Bloom and Bartelmetz, 1940. Am. J. Anat. 67.) (C) Differentiation of blood cells and blood vessel endothelium in a

blood island of chick embryo yolk-sac area.



terrestrial form, Rana temporaria, the bone marrow functions in this capacity as it does in the adults of reptiles, birds, and mammals. In the adult reptile and bird, the bone marrow seems to function in the production of all types of blood cells. In the mammal, the bone marrow possibly elaborates only erythrocytes and granular, white blood cells, while the lymphocytes probably are produced in other areas, such as the pharyngeal and palatine tonsils and lymph nodes, etc. In all vertebrates from the teleost fishes to the mammals, it is probable that scattered lymphoid tissue in various parts of the body functions in the formation of lymphocytes.

During the development of the early human embryo and later fetus, the following have been given as sites of blood -cell formation (Minot, ’12; Gilmour, ’41):

(a) yolk sac in embryos up to 3 mm., i.e., the end of the fourth week of pregnancy,

(b) mitosis of previously formed erythroblasts in general circulation, yolk sac, and chorion of embryos from 3 to 9 mm. in length,

(c) liver and yolk sac of 10- to 18-mm. embryos. In embryos of 470- to 546-mm. there is a gradual decrease in the liver,

(d) spleen, beginning in the 28-mm. embryo; thymus, and lymph glands in the 35-mm. and larger embryos,

(e) bone marrow during the third month and later.

3) Characteristics of Development of the Erythrocyte. Most vertebrates in the adult condition retain the nucleus in the erythrocyte or red blood cell. To this cell is given the function of carrying oxygen from the site of external respiration to the body tissues. It also is a factor in conveying carbon dioxide from the tissues to the site of external respiration. The oxygen-carrying capacity of the erythrocyte resides in the presence of the compound hemoglobin. Hemoglobin is a complex protein molecule, containing iron atoms. The iron atoms make it possible for the hemoglobin to convey oxygen.

In the adults of various amphibian species, there is a tendency for the red blood cell to lose its nucleus by various means (Noble, ’31, pp. 181-182). This tendency toward loss of the nucleus reaches an extreme form in Batrachoseps where more than 90 per cent of the red blood cells have lost their nuclei. In adult mammals, the mature erythrocyte loses its nucleus (column 6, fig. 333A) but it is retained in the early embryo.

4) Characteristics of Various White Blood Cells. White blood corpuscles or leukocytes vary greatly in number and in morphological features in all vertebrates. In general, the following two major groups of white blood corpuscles may be distinguished.

a) Granulocytes. Granulocytes are cells which arise from granuloblasts (columns 3, 4, and 5, fig. 333A). These cells are characterized by the



presence of an irregularly shaped nucleus and by a cytoplasm which possesses granules of various dimensions and staining affinities.

b) Lymphoid Forms. Lymphoid forms are of two types, namely, lymphocytes and monocytes. These cells arise from lymphoblasts and monoblasts respectively (columns 1 and 2, fig. 333A). The lymphocytes are small, rounded cells with a clear cytoplasm and a large nucleus. They are found in all vertebrates and are abundant especially in fishes and amphibia. Large numbers are found in the lymph nodes in various parts of the body. Monocytes are similar to the lymphocytes but are much larger and have a tendency to possess an irregularly shaped nucleus. Various hematologists hold that the monocyte is a special type of blood cell, distinct from other leukocytes and of a separate developmental origin.

D. Morphogenesis of the Circulatory System

1. Introduction

The major alterations of the basic arterial and venous conditions into the morphology present in the adult or definitive body form of the species occur during the larval period, or the period of transition from primitive embryonic body form to the definitive or adult form. This fact is true not only of the circulatory system but of all other organ systems as well (Chap. 11). The pronounced changes, therefore, which occur in the revamping of the basic, generalized condition of the circulatory system during the larval period should be regarded as transformation which adapts the basic embryonic condition to conditions which must be met when the developing organism emerges into the environment of the adult.

2. Transformation of the Converging Veins of the Early Embryonic Heart into the Major Veins which Enter the Adult Form of the Heart

a. Alteration of the Primitive Converging Veins of the Heart in the Shark, Squalus acanthias

An early stage of the developing venous circulation of Squalus acanthias is shown in figure 3 34 A. Only two veins are present, the primitive vitelline veins. They enter the sinal rudiment of the developing heart. Before the liver lobes form, the left vitelline vein develops a new venous sprout, the intestinal vein, which extends caudalward along the lateral aspect of the intestine to the developing cloacal area (fig. 334B). Here it forms a collar-like venous structure around the cloaca and continues back below the tail gut as the caudal vein. Meanwhile, the anterior, posterior, and common cardinal veins begin their development, and the liver also begins to form (fig. 334C). As the liver develops, two prominent liver lobes are elaborated (Scammon, T3 and the vitelline veins become surrounded by the developing liver trabeculae



(Chap. 13). During this process, the vitelline veins are fenestrated, and sinusoids are produced. These sinusoids connect with the right and left vitelline (hepatic) veins at the anterior end of the liver.

Posterior to the liver, the right and left vitelline veins form a collar around the duodenum as shown in figure 334C. The left portion of the duodenal collar then disappears, and the hepatic portal vein which receives blood from the developing stomach, pancreas, and intestine enters the liver as indicated in figure 334D.

As the above development progresses, three important changes are effected (fig. 334E):

( 1 ) The lateral veins along the lateral body wall arise and join the common cardinal veins near the entrance of the right and left vitelline (hepatic) veins;

(2) the intestinal vein loses its connection with the caudal vein; and

(3) the postcardinal veins extend caudally and connect with the caudal vein.

Meanwhile, the mesonephric kidneys begin to develop, and new veins, in the form of irregular venous spaces, form between the two kidneys. These new veins are the subcardinal veins. The subcardinal veins are joined by the internal renal veins which ramify through the kidney substance from the posterior cardinal veins. They course over and around the forming renal tubules (fig. 334F, G).

Later, the two subcardinal veins extend forward and by means of an anastomosis on either side connect with the posterior cardinal veins anterior to the mesonephric kidneys. As this transformation occurs, the segment of each posterior cardinal vein atrophies between the kidney and the point where the subcardinal venous anastomosis joins the posterior cardinal vein (fig. 334G).

While the above changes evolve, the anterior cardinal veins expand greatly over the dorsal pharyngeal area, where they form sinus-like spaces. These anterior cardinal venous sinuses receive the internal jugular veins from the brain region and various pharyngeal veins. Coronary veins and external Jugular veins also develop as shown in figure 334H.

b. Changes in the Primitive Converging Veins of the Heart in the Anuran Amphibia

1) Vitelline Veins. As in the shark embryo and in all other vertebrates, the vitelline veins of the frog or toad embryo are among the first blood vessels to be formed in the body. In frog embryos of about 3- to 4-mm. in length, the two vitelline veins begin to appear as irregular blood spaces along the ventro-lateral aspect of the midgut region, extending anteriad around the forming liver. At a point immediately anterior to the liver rudiment, these vessels fuse to form the endocardinal rudiment of the heart (fig. 332I-K).



Proceeding forward from the heart region, the two primitive subintestinal blood vessels continue forward below the rudiment of the foregut where they form the rudiments of the ventral aorta. They diverge and extend dorsad around the foregut to the dorsal area of the foregut. These vessels which thus pass around the foregut represent the third pair of aortal arches, i.e., the first pair of branchial aortal arches (fig. 335A). The first branchial aortal arches join the forming dorsal aortae. The dorsal aortae form first as irregular blood spaces, extending along the primitive gut from below the forming brain posteriad to the midgut area. Here they diverge to give origin to the vitelline arteries which ramify over the yolk substance of the midgut and there anastomose with branches of the vitelline veins.

About the time of hatching, the two vitelline veins become enmeshed in the substance of the developing liver, and the vitelline veins gradually become divided into three groups (fig. 335B):

(a) a right and left vitelline vein between the liver and the sinus venosus of the heart,

(b) the veins within the liver which form an irregular mesh work, and

(c) the two vitelline veins, posterior to the liver substance.

The left vitelline vein, anterior to the liver, soon atrophies and becomes fused with the right vitelline vein as indicated in figure 335C and D. The right vitelline vein thus receives the hepatic veins. Within the liver substance, the two vitelline veins break up into smaller veins to form ultimately the sinusoids of the liver (fig. 335C). Posterior to the liver, the vitelline veins form the hepatic portal and intestinal veins (fig. 335C).

2) Lateral (Ventral Abdominal) Veins. The lateral veins form first as two minute veins, which extend posteriad from the lateral ends of the sinus venosus of the heart. Eventually they unite with the iliac veins as shown in figure 335D.

Fig. 334. The developing venous system in Squalus acanthias. (Modified from Hochstetter, ’06.) (A) An early stage in the development of the venous system. The two

primitive vitelline veins only are present. (B) Later stage in development of vitelline veins. (C) Early stage in development of hepatic portal system. A venous ring is formed around the duodenum. Anterior and posterior cardinal veins are evident. (D) Later stage in the hepatic-portal system development. Left segment of duodenal collar has disappeared. Observe that the efferent hepatic veins (V. hepaticae revehentes) represent the right and left vitelline veins between the liver lobes and the sinus venosus, whereas the afferent hepatic veins (V. hepaticae advehentes) are the vitelline veins just posterior to the liver. (E) Lateral veins make their appearance. Posterior cardinal veins join veins around the cloacal area and thus assume responsibility for venous drainage of the tail region, and the intestinal vein in consequence loses its connection with the caudal vein of the tail. (F) Subcardinal veins appear between the kidneys. (G) Subcardinal veins make connection with posterior cardinal veins. Posterior cardinal veins regress anterior to the mesonephric kidneys where the posterior cardinal and subcardinal veins anastomose. (H) Mature plan of the venous system showing the converging veins of the heart. Hepatic portal vein omitted.




Anteriorly, the two lateral (ventral abdominal) veins lose their connection with the sinus venosus and merge together to form one ventral abdominal vein; the latter acquires a connection with the hepatic portal vein near the liver. A ventral abdominal circulation is established thus between the hepatic portal system and the iliac veins (fig. 335E, F).

3) Formation of the Inferior Vena Cava. The inferior vena cava is a vessel not found in the venous system of the developing shark. It is a blood vessel associated with and characteristic of lung breathers. As such, the inferior vena cava appears first among the vertebrates in the lungfishes (Dipnoi) and it functions to shunt the blood from the posterior regions of the body over to the right atrial portion of the heart. That is, the inferior vena cava is a vessel correlated with the division of the heart into two parts. One part is devoted to getting the non-oxygenated systemic blood into the lung region, while the other part functions to propel the aerated blood from the lungs into the head region and other parts of the body. This division of labor within the heart is not necessary in strictly gill-breathing fishes, such as the sharks and teleosts, and, in consequence, an inferior vena cava is not developed in these vertebrates.

The formation of the inferior vena cava in the anuran amphibia is shown in figure 335C-G and need not be explained further. It is to be observed that it forms from four segments:

( 1 ) a right vitelline vein,

(2) an hepatic segment,

(3) a segment which extends posteriad from the liver to the fused subcardinal vein, and

(4) the subcardinal vein, (Consult figure 335E.)

4) Formation of the Renal Portal System. The renal portal system is inaugurated among the cartilaginous fishes (i.e., the shark group). It does not exist in cyclostomes. As shown in figure 334 relative to the developing shark embryo, it results from the formation of the subcardinal veins, accompanied by the obliteration of the anterior portions of the posterior cardinal veins.

Fig. 335. Developing venous vessels in the anuran amphibia. (B-G, redrawn and modified from Kampmeier, 1920, Anal. Rec. 19; H, redrawn from Kampmeier, 1925, J. Morph. 41; I, redrawn from Goodrich after Kerr, 1930, Studies on the Structure and Development of Vertebrates, Macmillan, Ltd., London.) (A) Primitive plan of early circulation in frog embryo. The relationship of the primitive venous system shown in B to the rest of the vascular system is evident. (B) Plan of venous system of 4 mm. embryo of the toad, Bufo vulgaris. (C) Plan of venous system of 6 mm. embryo of the toad, Bufo vulgaris. (D) Plan of venous system of 15 mm. embryo of the toad, Bufo lentiginosus. (E) Plan of venous system of 18 mm. embryo of the toad, Bufo lentigirtosus. (F) Plan of venous system of young toad of Bufo lentiginosus, immediately after metamorphosis. (G) Plan of venous system of mature Rana pipiens. (H) Left posterior lymph hearts of an adult Rana pipiens. (1) Internal structure of mature frog heart.



The blood from the tail and posterior trunk region of the body thus must pass through the small blood vessels within the kidney substance. Here waste materials and excess water are extracted before the blood is passed on to the heart and aeration systems. The renal portal system is developed exceptionally well in the embryos and adults of fishes and amphibia. It is inadequately developed in the adult reptile, and it is questionable whether or not the poorly developed, renal portal system functions in the adult bird. The adult mammal does not possess this system. However, the embryos of all reptiles, birds, and mammals possess a renal portal system wherein blood is shunted through the kidney substance from the posterior cardinal veins into the subcardinal complex. It is a most transient affair in the mammalian embryo. The development of the renal portal system in the anuran embryo is shown in figure 335C-E. Observe that pronephric and mesonephric renal portal systems are developed.

5) Precaval Veins. The formation of the precaval veins is shown in figure 335B-G. It is to be observed that the common cardinal veins become transformed into the anterior or precaval veins, while the anterior cardinals persist as the internal jugular veins.

c. Changes in the Primitive Converging Veins of the Heart in the Chick

1) Transformation of the Vitelline and Allantoic Veins: a) Vitelline Veins. The vitelline veins in the developing chick first make their appearance as two delicate capillaries, one on either side of the inner wall of the anterior intestinal portal in blastoderms of 26-28 hours of incubation. At this time there are about four pairs of somites present. These minute blood vessels are intimately associated with the entoderm of the anterior intestinal portal, and eventually come to lie side by side immediately below the foregut as the anterior intestinal portal recedes caudally. At about 27-29 hrs. of incubation, or when the embryo has about five to six pairs of somites, the two splanchnic layers of the hypomeric mesoderm, in the area where the heart is to form, begins to cup around and enclose the two vitelline capillaries (fig. 332L). A little later, at about 29-33 hrs. of incubation, these two splanchnic mesodermal layers begin to fuse above and below the vitelline capillaries (fig. 332M). At 33-38 hrs. of incubation, or when nine to ten pairs of somites are present, a simple, tubular heart is present which contains the rudiment of the endocardium within in the form of the two fused or fusing vitelline capillaries. This endocardial rudiment is enclosed by the hollow, tube-like epimyocardial rudiment derived from the fused layers of splanchnic mesoderm (fig. 336A).

At about 33-38 hrs. of incubation (fig. 336A), the primitive circulatory system consists of the following:

(1) Two vitelline veins which converge to enter the forming heart just anterior to the intestinal portal;

(2) the primitive tubular heart;

morphogenesis of circulatory system


(3) two delicate capillaries, the future ventral aortae, course anteriad from the heart below the foregut. As the ventral aortae approach the anterior limits of the foregut they diverge and travel dorsad as the mandibular aortal arches, one on either side of the gut tube, to the dorsal region. In the dorsal area of the foregut the mandibular aortal arches become continuous with

(4) the dorsal aortae. These two delicate vessels lie upon the foregut on either side of the notochord, and extend caudalward into the region of the developing midgut.

During the period of 40 to 50 hours of incubation the following changes occur in the above system (fig. 336B and B'):

( 1 ) The rudimentary vitelline arteries extend outward over the yolk-sac area from the dorsal aortae, forming many small capillaries.

(2) The anterior and posterior cardinal veins and connecting intersegmental veins are established and unite with the sinus venosus by means of the common cardinal vein (fig. 336B').

(3) The vitelline veins extend outward over the blastoderm and continue anteriorly around the head area as the anterior vitelline veins. The latter veins unite with the circumferential blood sinus. A complete circulation through the embryo and out over the yolk-sac area is thus effected.

During the early part of the third day of incubation the right and left vitelline veins begin to fuse in the area just posterior to the heart. This fusion forms a single vein, the ductus venosus (fig. 337A). The latter structure joins the sinus venosus of the heart. Posteriorly, the vitelline veins make a secondary connection with the developing posterior vitelline or omphalomesenteric veins which extend backward along the sides of the midgut to the area where the vitelline arteries leave the dorsal aortae. At this point each omphalomesenteric vein turns sharply laterad and courses along the pathway of a vitelline artery (fig. 336C).

At the end of the third day of incubation the ductus venosus is present as an elongated structure lying between the anterior intestinal portal and the heart. A posterior vitelline vein continues posteriad from the ductus venosus around each side of the anterior intestinal portal (fig. 336D). As observed in Chapter 13, during the third and fourth days of incubation the liver rudiment begins to form. In doing so, the trabeculae of the liver surround the ductus venosus. The immediate segment of the ductus venosus which becomes surrounded by the forming liver substance forms the meatus venosus. As development of the liver proceeds, two main groups of veins develop in the liver substance (fig. 337B, D): (1) An anterior efferent group of hepatic veins which drain blood from the liver and (2) a posterior afferent set of hepatic


OORSAt aorta






Fig. 336. Early development of the circulatory system in the chick. (A) Primitive vitelline (omphalomesenteric) veins, heart, ventral aorta, and the first or mandibular pair of aortal arches. About stage 10 of Hamburger and Hamilton, 1951, J. Morph. 88. Approximately 33-38 hrs. of incubation. (A') Lateral view of same. (B) Lateral view of chick circulatory system of about 45-50 hrs. of incubation. (About Hamburger and Hamilton stage 13.) (B') Same, showing common cardinal vein (duct of Cuvier).

(C) Circulatory system of chick during early part of third day of incubation. (About Hamburger and Hamilton stage 15.) (D) Circulatory system of chick embryo about

72 hrs. incubation.




veins, representing branches of the hepatic portal vein. The latter brings blood from the stomach and intestinal areas to the liver.

During the fifth to seventh days of incubation, the afferent and efferent sets of hepatic veins develop profuse branchings, and venous sinusoids are formed within the liver substance between these two sets of veins. Meanwhile, the meatus venosus within the liver atrophies and a complete hepatic portal system is established between afferent and efferent hepatic veins during the seventh and eighth days of incubation as shown in figure 337E.

While the above changes in the liver are emerging, changes in the omphalomesenteric veins, posterior to the liver substance, are produced as shown in figure 337A-E. By the fifth day, a new vein, the mesenteric vein, is formed (fig. 337D), which begins to drain blood from the developing midgut and hindgut areas. By the eighth day, the mesenteric vein is a prominent structure (fig. 337E). At this time, the blood from the yolk sac, via the omphalomesenteric veins, and that from the mesenteric vein must pass through the liver sinusoids en route to the efferent hepatic veins (fig. 337E).

b) Allantoic Veins. The two allantoic or lateral veins begin to develop during the third day of incubation, and, by the end of this day, two delicate blood vessels extend along the lateral body wall, reaching back toward the hindgut area (figs. 336D; 337B). During the fourth day (fig. 337C), the caudal ends of the two allantoic veins begin to ramify within the walls of the allantois. A secondary attachment to the hepatic veins within the liver is established also at this time (fig. 337C). During the late fourth day and the fifth day of incubation, the right allantoic vein degenerates, and the proximal portion of the left allantoic vein loses its connection with the common cardinal vein (fig. 337D). During the seventh and eighth days (and until the time of hatching), the passage of blood from the allantois through the liver to the vena cava inferior is as indicated in figure 337E. The portion of the allantoic vein extending anteriorly from the umbilical area to the liver persists after hatching and drains blood from the midventral portion of the body wall. It is called the epigastric vein (fig. 3371).

2) Formation of the Inferior Vena Cava. The formation of the inferior vena cava of the chick is shown in figure 337F-I and needs no other explanation. It is to be observed that, following the degeneration of the mesonephric kidneys and the ascendancy of the metanephric kidney, the passage of blood by way of the renal portal system through the mesonephric kidney is abated. In the newly hatched chick, a much-weakened, renal portal system is established via the renal portal vein (fig. 3371J However, most of the blood through this vein passes directly into the common iliac vein and not through the kidney substance.

3) Development of the Precaval Veins. The precaval veins are the direct descendants of the anterior cardinal and common cardinal veins as indicated in figure 337F-I. In figure 3371, it is to be observed that the caudal ends of















' PORTAL !â–











LEFT allantoic R | \ >











I /I kidney \ \ /



f VEIN^^


\°®Java)7 hepatic 1


\ anastomosisJJ \ 1 1 SUBCARDINAL'





( anterior







Fig. 337. Ventral views of developing allantoic, hepatic portal, and inferior caval veins in chick. (Diagrams C and D are adapted from figures in Lillie, 1930, The Development of the Chick, Henry Holt, N. Y., after Hochstetter; diagrams F-H are adapted, considerably modified, from Miller, 1903, Am. J. Anat. 2.) (A) Diagram of converging veins

of heart during early third day of incubation. (B) Same at end of third and early fourth days. (C) Middle fourth day. (D) End of fourth and early fifth days. (E) Seventh to eighth days. (F) Development of inferior vena cava at end of fourth and beginning of fifth day of incubation. (G) Same, 6-7 days. (H) Same, fourteenth day. (I) Same at about hatching time, 20-21 days.




the posterior cardinal system function to drain the blood from the caudal end of the body and posterior appendages, while the anterior cardinal veins and common cardinal veins function to drain the blood from the head, neck, and forelimb areas.

d. The Developing Converging Veins of the Mammalian Heart (e.g., Human)

The formation of the hepatic portal system in the human embryo is shown in figure 338G, H, and that of the inferior and superior venae cavae is shown in figure 338 A-F. The general principles of venous development, described in the previous pages of this chapter, apply here, and descriptive matter is not needed to supplement the accompanying figures. It is worthy of mention, however, that two additional veins are introduced in the abdominal area of the embryo, namely, the two supracardinal veins. These veins persist as a part of the vena cava inferior and azygos veins. Anteriorly, the two precavae, so prominent in the lower vertebrates, including the birds, are displaced partially by the formation of an anastomosing vein from the left to the right side with the dropping out, to a considerable extent, of the proximal portion of the left precava. Thus, the common cardinal vein on the right side comes to function as the proximal portion of the single superior or anterior vena cava, while the common cardinal vein on the left side comes to form the coronary sinus of the heart, and occasionally as a variant, the oblique vein of the left atrium.

3. Development of the Heart a. General Morphology of the Primitive Heart

In the vertebrate group, two types of hearts are present, namely, lymp h hearty {fig. 335H) and the heart of the arteriovenous system. The heart of the arteriovenous system is a centralized, well-muscularized mechanism, placed ventral to the esophageal segment of the gut in the anterior extremity of the coelomic cavity. Its function is to receive blood from the veins of the body and to propel it forward toward the anterior or head region. Fund amen tally, the ern bryon ic Jieart of the arteriovenous system is a tubular affair, composed of four segments:

(1) a thin-walled sinus venosus or caudal portion of the heart, connecting with a series of converging veins,

(2) the atrium, a segment lying anterior to the sinus,

(3) the ventricle, lying anterior to the atrium, and

(4) the bulbus cordis.

The ventricle and, to some extent, the bulbus cordis of the embryonic heart later develop the structures which act as the main propulsive mechanism of the heart, while Ihe sinus and atrium give origin to the blood-receiving areas.



b. The Basic Histological Structure of the Primitive Embryonic Heart

Structurally, the embryonic heart is composed of two parts. An inner delicate lining, the rudiment of the endocardium, forms as a result of the fusion of the vitelline blood capillaries in the immediate area of the forming heart. The endocardium thus is composed of endothelium (fig. 332F-M). Surrounding the endocardial rudiment, there is the epimyocardium derived from the ventro-mesial portions of the hypomeric (splanchnopleural) mesoderm which extends ventrally from the foregut in this area (fig. 332F-M). Basically, the mesial walls of the two hypomeric areas of the mesoderm which lie below the foregut in this region constitute the ventral mesentery of the primitive gut. Consequently, the epimyocardium of the primitive heart may be regarded as modified ventral mesentery. That portion of the ventral mesentery which is dorsal to the forming heart forms the dorsal mesocardium, while that part which extends ventrally below the heart forms the ventral mesocardium. The latter is a transient structure, no sooner formed than obliterated in most instances. The dorsal mesocardium tends to persist for a time, more in some species than in others. Caudally, the posterior lateral areas of the sinus venosus project the splanchnopleural mesoderm laterally to contact the lateral somatopleural mesoderm with which the splanchnopleural mesoderm fuses. This outward extension of the caudo-lateral edges of the sinus venosus produces a bridge across the coclomic space from the lateral body wall to the sinus venosus. These bridges on either side across the primitive coelom form the lateral mesocardia. Through these mesocardial bridges, the common cardinal veins empty their contents into the heart.

Fig. 338. Changes in the converging veins of the heart in the mammalian embryo. (Redrawn and modified from Patten, 1946, Human Embryology, Blakiston, Philadelphia, after McClure and Butler.) (A F) Developmental changes in converging veins of the human heart. Primitive converging veins of the heart shown in black; hepatic segment of inferior vena cava shown in white with coarse stipple; subcardinal veins shown in light stipple; supracardinal veins in white with crossed lines. (Note: the author assumes the responsibility for adding a vitelline venous segment to the anterior end of the developing inferior vena cava. As a result of observations on developing pig, cat, and opossum embryos, the author is convinced that a vitelline segment is contributed to the developing posterior vena cava in the mammal.) (A) Primitive basic condition. (B-F) Later stages as indicated. (F) Adult condition. The following contributions appear to enter into the formation of the inferior vena cava, viz., (1) a very short vitelline segment; (2) an hepatic segment; (3) an anastomosis between the hepatic segment and the subcardinal interrenal anastomosis; (4) a subcardinal-supracardinal anastomosis; (5) a right supracardinal segment caudal to the kidneys; and (6) a posterior cardinal contribution in the pelvic area. Note also that the azygos vein is formed from the anterior end of the right posterior cardinal vein plus the right supracardinal with its connections with the hemiazygos vein. Observe further that the superior vena cava is composed of the right common cardinal vein from the area of juncture with the azygos vein to the point of its entrance into the right atrium. (G-J) Formation of the hepatic portal vein in the pig. (Redrawn and slightly modified from Patten, 1948. Embryology of the Pig, Blakiston, Philadelphia.



omphalomesenteric VI





internal jugular veins





























omphalomesenteric VEINS





Fig. 338. (See facing page for legend.)




c. Importance of the Septum Transversum to the Early Heart

There is another structure which is important to the primitive embryonic heart and to its later development. This structure is the primary septum transversum or the mesodermal partition which forms across the coelomic cavity, below (ventral) to the lateral mesocardia. It forms not only a partition or bulwark, separating the developing liver substance from the primitive heart, but it is also a suspensory ligament for the caudal end of the sinus venosus and the converging veins of the heart. (See Chap. 20.)

d. Activities of Early-Heart Development Common to All Vertebrates

The early stages of heart development, following the formation of the basic rudiments mentioned above, are essentially the same for all vertebrates. These changes, which result in the formation of a sigmoid or S-shaped structure, are as follows (see figs. 336, 339):

( 1 ) The dorsal mesocardium soon disappears for most of its extent, and the primitive heart tube begins to elongate and to change its shape rapidly.

(2) The ventricular portion bends ventrally and to the right and, at the same time, grows posteriad, becoming thick-walled.

(3) The atrial area expands laterally, grows forward dorso-anteriad over the ventricular area; and at the same time forms two lateral lobes.

(4) The sinus venosus remains thin walled and rigidly attached to the septum transversum. The latter, in all vertebrates above the fishes, bends forward along its upper margins during the early period of development.

(5) The bulbus cordis extends slowly and becomes a thickened anterior continuation of the heart from which arise the ventral aortic roots.

e. Development of the Heart in Various Vertebrates

From the generalized, S-shaped, basic condition, the hearts of the various vertebrate groups begin to diverge in their development as follows:

1) Shark, Squalus acanthias. Starting as a straight tube when the embryo is 5.2 mm. long (fig. 339A), the ventricular portion begins to bend toward

Fig. 339. Early stages in morphogenesis of various vertebrate hearts. (A-C) Stages in heart development in Squalus acanthias. (Redrawn from Scammon, 1911, Chap. 12, in Normentafeln Entwichlungsgeschichte der Wirbeltiere by F. Keibel, G. Fischer, Jena.) (I>-F') Heart development in the frog, Rana pipiens. (D-F) Left lateral views; (F') ventral view. (G-K) Heart development in the chick, ventral views. (H-K, redrawn from Kerr, 1919, Text-Book of Embryology, vol. 11, Macmillan and Co., Ltd., London, after Greil.) (L- O) Heart development in the human embryo, ventral views. (Redrawn from Kramer, 1942, Am. J. Anat. 71. L, after Davis, modified; M, after Tandler, modified; N, after Waterston, modified.) Observe that ventricular end of the original bulbus cordis, i.e. the conus portion, contributes to the right ventricle in diagrams N and O.









artery V right


^ ROOT / T



Fig. 339. (See facing page for legend.)




the right and ventrad in the embryo of 7.5 mm. At 15 mm., the heart appears as indicated in figure 339B, while, at 20.6 mm., it assumes the general appearance of the adult form (fig. 339C). It is to be noted that the ventricular portion of the heart does not bend as dramatically toward the right as in the chick or mammalian heart. In the embryo of 37 mm., the heart already has attained the characteristics of the adult form. The following developmental features are present. The bulbus cordis has transformed into the anterior contractile chamber, the conus arteriosus; the ventricular area has developed a pronounced musculature; the atrium is thin walled and bilobed, while the sinus venosus is cone shaped with its base applied against the septum transversum. Right and left valves guard the sinu-atrial entrance. A series of semilunar or pocket valves arc arranged around the atrioventricular orifice, while, more anteriorly, cup-shaped valves are forming in transverse rows along the inner walls of the conus arteriosus.

2) Frog, Rana pipiens. At 4'/i mm. in length, the heart is present as a simple straight tube (fig. 339D). At 5 mm., it begins to bend, the ventricular area moving ventrad and toward the right, and the atrial area and sinus venosus moving anteriad over the ventricular area (fig. 339E). At 7 mm., the heart has assumed the typical S-shaped condition of the adult form, and constrictions appear between the atrium and ventricle (fig. 339F). At this time, also, a median septum begins to divide the atrial chamber. The atrial septum begins as a fold from the antero-dorsal wall of the atrium and grows ventrad and posteriad to divide the atrium into a larger right atrium and a smaller left artium. Moreover, as the atrial septum is developed, it forms to the left of the opening of the sinus venosus into the atrium. Therefore, in the 8- to 10-mm. tadpole, the opening of sinus venosus into the atrium is entirely restricted to the right atrium, and the flow of venous, systemic blood is directed toward the right side of the heart. At about this time, also, the formation of the vena cava inferior proceeds rapidly. (See fig. 335.) At 8 to 10 mm., the lung buds (Chap. 14) expand rapidly, and the pulmonary veins begin to bring back blood from the lungs. The pulmonary veins empty into the left atrium (fig. 257B).

During the late tadpole stages and metamorphosis, internal changes occur which transform the heart into a complicated mechanism, designed to separate and project the oxygenated blood anteriad toward the head and into the systemic vessels; the non-oxygenated blood from the sinus venosus passes into the pulmocutaneous arteries. These different blood currents within the heart are made possible largely by the modification of the internal walls of the primitive bulbus cordis into the highly complicated mechanism of the contractile conus arteriosus. Aside from a series of small pocket valves, the dorsal wall of the conus forms an elongated spiral valve which functions to separate its channel into two parts. The non-oxygenated blood is projected dorsally to the spiral valve and into the pulmocutaneous vessels by the spiral



valve, while the oxygenated blood passes ventrally to the spiral valve and into the arteries coursing toward the head and into the systems (fig. 3351). This condition of the conus is present also in urodeles with well-developed lungs, but, in urodeles without well-developed lungs, the spiral valve is absent and the interatrial septum may regress (Noble, ’31, pp. 187-194).

3) Amniota. The heart of reptiles, birds, and mammals differs from the heart of the Amphibia in that a mechanism is present which separates, more or less completely, the oxygenated blood from the non-oxygenated blood. For example, the heart of birds and mammals is a four-chambered affair as an interventricular septum divides the primitive ventricle into two separate compartments while an interatrial septum separates the primitive atrium into two atria. A double heart is produced in this manner wherein the nonoxygenated blood returning from the organ systems passes through the right atrium and ventricle en route to the lungs while the oxygenated blood from the lungs journeys through the left atrium and ventricle on its way back to the organ systems. In the heart of birds and mammals, it is to be observed also, that only two arterial channels convey blood from the heart; namely, a pulmonary arterial trunk and a systemic arterial trunk. Another feature is present in the heart of the birds and mammals which serves to distinguish it from the hearts found in all lower vertebrates, in that the sinus venosus is absorbed almost entirely during embryonic development into the wall and structure of the right atrium.

Turning now to a consideration of the hearts of reptiles we find that the turtles and snakes possess a heart with two atria and a ventricular region divided rather completely into two ventricles. However, the interventricular septum is slightly incomplete in the region near the atria, and some leakage of blood between the two ventricles is possible. In the crocodilians the interventricular septum is completely developed, but a small opening, the fommen of Panizza, is present at the bases of the two systemic arterial trunks. This foramen arises as a secondary perforation later in development and does not represent an incompleteness of the interventricular septum. In the reptilian heart the sinus venosus retains its identity as a separate chamber of the heart. Furthermore, contrary to the conditions found in the avian and mammalian heart, three arterial trunks convey blood away from the ventricles. Two of these vascular trunks come from the right ventricle, and one from the left ventricle, for a pulmonary trunk conveys blood from the right ventricle to the lungs, while a systemic aortic root also carries blood from the right ventricle to the abdominal aorta. From the left ventricle, on the other hand, blood is propelled through a single aortic root to the head, forelimbs, and abdominal aorta (fig. 341H).

a) Heart of the Chick. The heart arises as a simple tube during the second day of incubation (fig. 339G). At the end of the second day and during the third day, the primitive ventricle bends to the right, and the atrium



begins to travel forward above the ventricle (figs. 336C; 339^1"). At the end of the third day, the heart attains the typical sigmoid or S-shaped condition which arises as the first major step in heart development in all vertebrate embryos. During the fourth day of incubation, the atrial area expands into two main lobes, the beginnings of the right and left atria; the ventricular area expands greatly and thickens; and the bulbus cordis lies in the median line between the developing atria (fig. 3391). The position of the various parts of the heart on the whole assumes more nearly the adult condition.

Internally, toward the end of the fourth day, an interatrial septum begins to develop from the dorso-anterior area between the two atrial lobes, slightly to the left of the opening of the sinus venosus. The septum continues to form posteriad toward the narrowed atrio-ventricular opening between the atria and the forming ventricles. Simultaneously in the atrioventricular opening, two endocardial thickenings, the endocardial cushions, arise, one dorsal and one ventral. At the apex of the ventricle, an interventricular septum appears and grows forward toward the atrioventricular opening (fig. 340G).

During the fifth and sixth days, the two endocardial cushions grow together and separate the atrioventricular canal into two passageways by the formation of a cushion septum. The atrial septum grows toward the endocardial cushion area and unites with the cushion septum. However, the atrial septum never is completed during embryonic life, as small openings or fenestrae, appear in the septum permitting blood to pass through the septum. During the last week of incubation, the fenestral openings in the atrial septum become much smaller and completely close shortly after hatching. The ventricular septum, meanwhile, grows forward to unite with the cushion septum. Up to the fifth day, but one passageway leaves the heart via the developing bulbus cordis and ventral aorta. However, during the fifth day, beginning at the area just anterior

Fig. 340. Early stages in morphogenesis of various vertebrate hearts {Continued). (A-E) Internal changes in the developing heart of the pig. (A-D, redrawn from Patten, 1948. Embryology of the Pig, 3d edit., Blakiston, Philadelphia.) (A) Diagram of 3.7 mm. pig embryo heart, ventral wall removed. (B) Similar diagram of 6 mm. pig heart. (C) Similar diagram of 9.4 mm. pig heart. (D) Similar diagram of dissected pig fetal heart shortly before birth. (E) Schematic drawing of dissected 18 mm. pig heart viewed from right side with walls of right atrium and right ventricle removed. Observe that the bulbus cordis has divided into two vascular trunks. (F) Dorsal aspect of the heart of an 11 wk. (60 mm.) human embryo. (Redrawn and modified from Patten, 1946. Human Embryology, Blakiston, Philadelphia.) The contraction wave of the heart beat is indicated by heavy arrows. Starting at the sinus node situated in the dorsal wall of the right atrium, the contraction wave spreads over the atrial walls and also to the atrioventricular node located in the atrial septum from whence it travels distally through the ventricular tissue. (G) The developing chick heart, of about 6-7 days. Right walls removed to show developing cardiac septa. The ventricular septum is still incomplete, and the atrial septum is fenestrated. (This figure has been modified considerably from Kerr, 1919. Text-Book of Vertebrate Embryology, vol. 11, Macmillan, Ltd., London, after Greil.) (H) Adult heart of the South American lung fish, Lepidosiren paradoxus, right side removed. (Redrawn from Robertson, 1913. Quart. J. Micros. Sci., 59.)




Fig. 340. (See facing page for legend.)




to the sixth pair of aortal arches, a spiral septum begins to form within the caudal portion of the ventral aortal sac and the bulbus cordis. This septum grows caudalward within the bulbus in a spiral manner, separating the pulmonary trunk ventrally and the root of the systemic aorta dorsally. It continues backward toward the interventricular septum and there unites with a similar septum at the caudal end of the bulbus. The original bulbus cordis thus becomes divided at about the seventh day of incubation into two separate vessels which course spirally around each other, namely, a pulmonary trunk which unites with the right ventricle and an aortal root which is continuous with the left ventricle (fig. 339J).

Coincident with the above changes, the valves of the heart are developed. As the spiral septum is developed in the region of the bulbus cordis, three semilunar or cup-shaped valves appear at the base of each of the divisions of the bulbus. That is, at the base of the aortic root and also at the base of the pulmonary trunk. These valves prevent the backward flow of the blood from the aortic root into the left ventricle and from the pulmonary trunk to the right ventricle. When the original atrioventricular opening is divided into two atrioventricular openings by the formation of the cushion septum, the atrioventricular or cuspid valves are formed in the two atrioventricular openings. These valves prevent the backflow of blood into the atria from the ventricles. At the opening of the sinus into the right atrium, the right and left sides of the opening enlarge and produce folds which project inward into the atrium. These folds form the sinu-atrial (sinu-auricular) valves. During the last week of incubation, a third valve, the Eustachian valve or sinus septum, arises as a fold from the dorsal aspect of the sinus which projects into the right atrium between the openings of the vena cava inferior and the right and left venae cavae superior (precavac). It divides the sinu-atrial opening.

As hatching time approaches, the sinus becomes incorporated almost completely into the walls of the right atrium. A small portion of the sinus probably is incorporated into the cardiac end of the left precaval vein. The sinu-atrial valves also disappear and the fenestrae of the atrial septum gradually close.

b) Mammalian Heart: 1) Early Features. The early development of the mammalian heart (fig. 339) follows the general pattern of the developing heart of lower vertebrates. A primitive tubular heart composed of a sinus venosus, atrium, ventricle and bulbus cordis is evolved. This simple tubular heart is followed by a typical sigmoid-shaped structure in which the two atrial lobes hang ventrally, one on cither side of the bulbus cordis, while the ventricular region projects caudo-ventrally (fig. 339N). The sinus venosus is much smaller, relatively speaking, than that formed in lower vertebrates and tends to be placed toward the right side of the heart in relation to the future right atrium. By the fifth and sixth weeks in the human (fig. 3390), the heart attains outwardly the general appearance of the four-chambered heart.

2) Internal Partitioning. The internal divisions of the heart begin to appear



in the human at about the fifth week, and in the pig at about 4 mm. or 17 days. This process is similar in the human and the pig, and while the following description pertains particularly to the pig it may be applied readily to the developing human heart. In the pig, as in the chick, a crescentic fold or septum of the atrial chamber begins to grow caudally toward the atrioventricular opening from the antero-dorsal region of the atrium. This septum forms the septum primum or interatrial septum I (fig. 340A). As this septum grows caudad, two thickenings, the endocardial cushions, one dorsal and one ventral, arise in the atrioventricular opening (fig. 340B) . The endocardial cushions fuse and divide the atrioventricular canal into two openings. The septum primum ultimately joins and fuses with the endocardial cushions, but the septum as a whole is incomplete, an interatrial opening being present (fig. 340C). Meanwhile, the sinus venosus shifts more completely toward the right atrium, and the opening of the sinus into the right atrium also shifts dextrally. This permits an enlarged area to appear between the interatrial septum and the valvulae venosae, or valves of the sinus venosus guarding the sinu-atrial opening. In this area, interatrial septum II or septum secundum, arises as a downgrowth from the atrial roof (fig. 340C, D). This second septum eventually produces a condition as shown in figure 340D. The arrow denotes the passageway or foramen ovale in the septum secundum and also the outlet for the blood into the left atrium over the dorsal part of the valve of the foramen ovale (valvula foraminis ovalis), derived from the atrioventricular end of septum I. This condition persists until birth. The valve of the foramen ovale derived from septum 1 prevents the backflow of blood from the left atrium into the right atrium.

The atrioventricular valves are shown also in figure 340D, together with the fibrous attachments of these valves to the muscular columns of the left and right ventricles. The atrioventricular or cuspid valves arise as thickened, shelf-like growths of connective tissue, to which the tendinous cords from the papillary muscles become attached. The left and right ventricles arc produced as in the chick by the upgrowth from the ventricular apex of the interventricular septum. In the human, the interventricular septum fuses with the endocardial cushions during the eighth to ninth weeks. The papillary muscles projecting inward into the ventricular cavities (fig. 340D) represent modifications of the trabeculae carneae (fig. 340B).

J ) Fate of the Sinus Venosus. The developing superior and inferior venae cavae open into the right horn of the sinus venosus. As the right atrium enlarges it absorbs this right horn into its walls and the venae cavae obtain separate openings into the right atrium (fig. 340D). The body of the sinus venosus becomes the coronary sinus which opens into the right atrium below the opening of the inferior vena cava. The coronary veins empty into the coronary sinus. The left horn of the sinus venosus may persist as a part of the oblique vein of the left atrium (fig. 340F).

/. Fate of the Segments of the Early Embryonic Heart in Various Vertebrates

Fishes Amph ibia Reptiles Birds Mammals

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4) The Division of the Bulbus Cordis (Truncus Arteriosus and Conus). The division of the bulbus cordis occurs synchronously with the above changes. Two internal ridges opposite each other are formed during this process. These ridges fuse and divide the bulbus in a spiral fashion into a dorsal aortic root and a pulmonary trunk as indicated in figure 340E. The pulmonary trunk opens into the right ventricle, and the aortic root opens into the left ventricle. Three cup-shaped, semilunar (pocket) valves are developed from internal ridges in the areas between the base of the aortic trunk and the left ventricle and between the base of the pulmonary trunk and the conus portion of the right ventricle (fig. 340E).

4. Modifications of the Aortal Arches

When the heart begins to form, its position is ventro-posteriorly to the developing pharyngeal area. As the pharyngeal region enlarges, the heart recedes, relatively speaking, and moves caudally. This caudal recession of the primitive heart in relation to the pharyngeal area is greater in fishes than in the amphibia and higher vertebrates. Therefore, the ventral aortae (and later ventral aorta) are longer in fishes than in other vertebrates. Actually, in the amphibia and particularly in the higher vertebrates, the primitive heart itself tends to lie below the pharyngeal area. Consequently, the bulbus cordis or anterior end of the primitive heart comes to lie below the midpharyngeal region, and the aortal arches in amphibia and in higher vertebrates arise from the anterior end of the primitive heart in bouquet fashion (figs. 34 IE, 342 A, E). On the other hand, in fishes, a single, elongated, ventral aorta is formed, which extends the length of the pharyngeal area. The developing heart is attached to its caudal end, and the aortal arches arise along its extent (fig. 341A).

The aortal arches arc paired vessels which run dorsally through the substance of the visceral arches. Six pairs of these arches are formed generally in the gnathostomous vertebrates, although some of them are transitory structures. The first, second, and fifth pairs of aortal arches are the most transitory in all forms above the fishes.

During development the aortal arches are modified differently in the various vertebrate groups. In fishes, a permanent, branchial mechanism is inserted midway along the branchial visceral arches. The aortal arch of each branchial visceral arch is broken up into an afferent vessel, passing from the ventral aorta to the branchial (gill) structure, and an efferent vessel, leading from the gill mechanism to the dorsal aorta (fig. 341B). In the majority of amphibia, the first, second, and third branchial aortal arches become involved temporarily in the development of gill mechanisms, although some, such as Necturus, retain the gills permanently. In higher vertebrates, none of the aortal arches are concerned with gill formation, and are, in consequence, transformed directly into the adult form.



The transformation of the aortal arches in the shark, frog, chick, and mammal is shown in figures 341 and 342. It is important to observe that, in those vertebrates possessing lungs, the pulmonary artery grows back from the sixth aortal arch. In a sense, however, the pulmonary arteries represent a direct caudal growth from the posterior ventral aortae, particularly in reptiles, birds, and mammals (fig. 342 A, B, C, E, F, G).

5. Dorsal Aortae (Aorta) and Branches

Two dorsal aortae arise first, one on either side of the notochord and above the primitive gut tube, and their origin is synchronous with the formation of the ventral, vitelline (subintcstinal ) blood vessels and the heart. Posterior to the pharyngeal area, the primitive dorsal aortae soon fuse to form a secondary vessel, the dorsal aorta, lying below the notochord. Anteriorly, in the pharyngeal area, they remain separate, and the cephalic end of each primitive dorsal aorta grows forward into the developing forebrain area. These forward growths of the primitive dorsal aortae into the forebrain area form the anterior rudiments of the internal carotid arteries. The primitive dorsal aortae, therefore, give origin to a single secondary vessel, the dorsal aorta, which is bifurcated at its cephalic end in the region of the pharyngeal area of the gut.

Aside from the cephalic ends of the internal carotid arteries, three main sets of arteries arise from the developing dorsal aorta:

1 ) Dorsal intersegmental arteries, passing between the somites and sending a dorsal branch toward the neural tube and epaxial musculature and a lateral branch into the hypaxial musculature (fig. 343A). The lateral branches develop into intercostal and lumbar arteries of the

Fig. 341. Modifications of the aortal arches. In the following diagrams, the aortal arches are depicted in such a way as to represent two parts, viz. an afferent system, conveying the blood from the heart to the branchial (gill) region, and an efferent system, leading the blood away from the branchial area. The afferent system of vessels is finely stippled, whereas the efferent system is ringed with lines. With the exception of certain lateral views all diagrams have been made from the dorsal view. ( A-D) Aortal vessel changes in embryos of Squalus acanthias. (A and B, adapted from actual conditions described by Scammon, 1911. See reference under Fig. 339.) (A) Generalized, basic

condition present in embryo of 15 mm. embryo. (B) Lateral view, 20.6 mm. stage. (C and D) The afferent and efferent systems in the adult form. D should be superimposed upon C. Diagrams C and D have been separated to minimize confusion. (E-G) Modifications of the aortal arches in the frog. The modifications of the aortal arches in the frog involve a complicated series of changes. In Fig. 335 (A) the simple tubular aortal arches are shown during the earlier phases of development. In Fig. 257 (B) a later stage is depicted. In the latter figure the aortal arches are separated into functional afferent and efferent vessels supplying the branchiae or gills. At the time of metamorphosis the vessels are reorganized, apparently, into tubular vessels according to the pattern shown in Fig. 341 (E). The transformations of the basic conditions shown in Fig. 341 (E) into the adult form are outlined in Figs. 341 (F and G). (H) The

three divisions of the bulbus cordis in the turtle.






Fig. 341. (See facing page for legend.)



adult. The arteries to the bilateral appendages arise as modifications of the lateral branches of the intersegmental arteries (fig. 343B, C').

2) Lateral arteries which are not as truly segmented as are the dorsal intersegmental arteries. They pass laterally into the developing nephrotomic structures (fig. 343A). The renal and genital arteries of the adult are derived from the lateral series of arteries.

3) Ventral arteries much fewer in number than the above-mentioned series (fig. 343A). The vitelline arteries of the yolk-sac area are the first of these ventral arteries to develop. In the Amniota, the umbilical or allantoic arteries also belong to the ventral series of arteries arising from the dorsal aorta. These vessels pass to the placenta or allantoic areas. The coeliac, superior mesenteric, inferior mesenteric, and umbilical arteries are the adult derivatives of the ventral series of arteries arising from the primitive dorsal aorta.

£. Development of the Lymphatic System

The lymphatic system often is called the white blood circulatory system because red blood cells are not present normally, its blood being composed of a lymph fluid and various types of white blood cells.

Lymph vessels are present in all gnathostomous vertebrates, particularly in the bony fishes and in amphibia, reptiles, birds, and mammals. They appear to be absent in cyclostomes. The lymphatic system is highly developed in the amphibia where it possesses lymph hearts, which actively propel the lymphatic fluid forward. Lymph hearts are found in the tail region of bird embryos, including the chick. However, lymph flow on the whole is of a sluggish nature. Lymph vessels never join arteries but connect in various regions with the veins. In larval amphibia and in certain adult species of amphibia, these connections with the venous system may be numerous.

Fig. 342. Modifications of the aortal arches (Continued). (A) Generalized, basic condition of the aortal arches in the chick embryo developed during the first 314 days of incubation. (B) Left lateral view of condition present during latter part of the third day. (C) Schematic representation of changes in aortal arches, dorsal aortae, and the aortal sac of the chick embryo after the first week and a half of incubation. Observe that each external carotid artery arises from the anterior end of a ventral aortic root plus an anastomosis with the common carotid segment. Note further that the right and left sixth aoral arches persist until approximately the twenty-first day (see diagram D). (Diagram C is based to some extent upon data supplied by Pohlman, 1920 . Anat. Rec. 18 .) (D) Dorsal view of adult condition of aortal-arch and bulbus cordis derivatives in the developing chick after hatching. (E) Generalized aortal arch condition in mammalian embryo. (F) Dorsal view of aortal arches of about 6 mm. human embryo. (G) Lateral view of same. (This figure redrawn and adapted from Patten, 1946 . Human Embryology, Blakiston, Philadelphia, after Congdon.) (H) Dorsal view of aortal arches of 14 mm. embryo. (I) Left lateral view of same. (This figure is redrawn and adapted from Patten, 1946 . Human Embryology, Blakiston, Philadelphia.) (J) Dorsal view of conditions present after birth. (See also Fig. 379.)


Fig. 342. (See facing page for legend.)




Two general views are held as to the origin of the lymphatic system. One view holds that lymphatic vessels develop independently of blood vessels and originate as small spaces in the mesenchyme, the mesenchymal cells flattening and forming an endothelial lining for the space (Huntington, T4). Such primitive lymph spaces fuse with nearby lymph spaces to form discrete channels (McClure, ’21). A second view maintains that the certain, small lymph sacs arise from small endothelially lined channels which are a part of the primitive venous plexuses in certain areas (Sabin, ’12, p. 709). Both views agree, however, that once formed, the primitive lymph vessels grow and spread by sprouting new channels from previously established vessels (Clark and Clark, ’32).

The first lymphatic capillaries appear to develop along the main veins. In certain regions, these capillaries give origin to the lymph sacs. Right and left jugular lymph sacs arise in the mammal along the anterior cardinal veins at the base of the neck (fig. 343D). These lymph sacs grow, expand, and coalesce with smaller adjoining lymph spaces. Various other lymph sacs arise, such as the subclavian lymph sac which is associated with the subclavian vein in the axillary region, the cisterna chyli which arises from the retroperitoneal, median lymph sac in the lumbar area, and the iliac lymph sacs which arise posterior to the retroperitoneal rudiment of the cisterna chyli. From these central lymph sacs, the peripheral lymph channels arise and grow rapidly in a distal direction. The thoracic duct comes into existence as a longitudinal vessel along the middorsal area of the body and together with the left jugular lymphatic trunk opens into the venous system near the junction of the internal and external jugular veins. The right jugular lymphatic trunk opens into the venous system similarly on the right side. From these main lymphatic areas, smaller peripheral channels arise as endothelial outgrowths. Valves develop within.

Fig. 343. Branches of dorsal aorta; lymphatic structures. (A) Diagram illustrating various branches of dorsal aorta. (B) Arteries of brain area, appendages, body wall and umbilical cord of human embryo of seven weeks. (Redrawn from Patten, 1946. Human Embryology, Blakiston, Philadelphia, after Mall.) (C and C') Two stages in development of forelimb arteries of pig: C, embryo of 4.5 mm.; C', embryo of 12 mm. (Redrawn from Woollard, 1922. Carnegie Contribution to Embryology, No. 70, Vol. 14.) (D) Formation of primitive lymph sacs in the mammal (cat). (Redrawn from

F. T. Lewis, 1906. Am. J. Anat. 5.) (E and E') Four stages in the development of a lymph node. (Redrawn from Bremer, 1936. A Text-book of Histology, Blakiston, Philadelphia.) Diagram E, to the left. Lymphatic vessels come to surround a mass of primitive lymphoid tissue composed of mesenchymal tissue and lymphocytes. Primitive connective tissue surrounds the mass. Diagram E, to the right. The ingrowing lymphatic channels break up the lymphoidal tissue with the subsequent formation of lymph sinuses. Observe that a peripheral lymph channel is established, and also that the surrounding connective tissue is beginning to form a surrounding capsule from which trabeculae are growing into the lymphoidal mass. Diagram E', to the left. Further development of growth changes shown in E, to the right. Diagram E', to the right. A loose meshwork of lymph channels and sinuses appears in the central portion or medulla of the lymph node, whereas the periphery or cortex is composed of secondary nodules separated into compartments by the ingrowth of trabeculae from the peripheral capsule.












Fig. 343. (See facing page for legend.)




A characteristic feature of the lymphatic system is the development of lymph nodes (lymph glands) along the lymphatic vessels. A lymph node is a small, rounded structure with lymph vessels entering it at various points (fig. 343E). From these lymph vessels, a flow of lymph oozes around a meshwork of lymphoid cords, contained within the lymph node. After passing through the meandering lymph spaces within the node, the lymph emerges from the opposite side of the lymph node into lymphatic channels.

Lymph nodes appear to arise from lymph sacs which are invaded by ingrowing mesenchyme and connective tissue. Lymphoblasts become associated with these connective-tissue ingrowths, and lymphocytes are differentiated in large numbers. Eventually the developing lymph node forms two areas, an outer cortex, containing dense masses of lymphocytes and an inner medulla, containing a loose meshwork of lymph channels and sinuses. Connective tissue forms a capsule around the lymph node from which partitions or trabeculae grow inward to divide the cortex into secondary nodules. Beneath the capsule, a peripheral lymph sinus is developed. Blood vessels enter the lymph node at the hilus and pass along the trabeculae to the secondary nodules. The returning blood vessels follow the same pathways.

The spleen is a large lymph gland attached to the omental derivative of the dorsal mesogastrium or peritoneal support of the stomach. It arises as a concentration of mesenchyme along the left aspect of the early mesogastrium. This mesenchymal mass eventually increases in size and projects from the surface of the mesogastrium from which it later becomes suspended by a constricted peritoneal support, the gastro-splenic ligament.

The mesenchymal mass of the developing spleen is well supplied with blood vessels, and a completely closed set of vascular channels is formed at first. Later, however, sinus-like spaces appear which unite with the closed vascular channels converting the closed system into one possessing open sinuses. Lymphoid tissue forms and masses of splenic corpuscles develop about the blood vessels. (Consult Maximow and Bloom, ’42, for detailed description of splenic structure.)

F. Modifications of the Circulatory System in the Mammalian Fetus

at Birth

Consult Chap. 22.

G. The Initiation of the Heart Beat

The first parts of the heart to be developed are the anterior regions, namely, the bulbus cordis and the ventricle. When the ventricular region is developed in the chick, it starts to twitch. Later when the atrial portion is formed, it commences to contract with a rhythm different from that of the ventricular area, and its beat supersedes that of the ventricle. Still later when the sinus venosus is established, it emerges with its own contraction rhythm, and this



rhythm then dominates the contraction wave which spreads forward over the heart. The area of the sinus continues to be the “pacesetter” of the heart beat throughout life, although in birds and mammals, the sinus is taken up into the posterior wall of the right atrium. In the mammal (fig. 340F), the sinus node, located in the right atrium, initiates, under normal conditions, each heart beat. The contraction stimulus spreads distally to the peculiar fibrous bundle, located in the atrial septum and the atrioventricular area. This bundle is known as the atrioventricular node, and its fibers descend into the muscles of the ventricular area, conveying the heart beat to the ventricles.

Though fibers from the autonomic nervous system reach the heart in the region of the right atrium and stimuli from these nerves may greatly affect the rhythm of the heart beat, the essential control of the beat lies within the heart’s own nodal system (fig. 340F).


Bloom, W. and Bartelmez, G. W. 1940. Hematopoiesis in young human embryos. Am. J. Anat. 67:21.

Clark, E. R. and Clark, E. L. 1932. Am. J. Anat. 51:49.

Gilmour, J. R. 1941. Normal haemopoiesis in intra-uterine and neonatal life. J. Path. & Bact. 52:25.

Hochstetter, F. 1906. Chap. IV in Handbuch der vergleichenden und experimentellen Entwickelungslehrc der Wirbeltiere by O. Hertwig. Gustav Fischer, Jena.

Huntington, G. S. 1914. Development of lymphatic system in amniotcs. Am. J. Anat. 16:127.

Jordan, H. E. and Speidel, C. C. 1923a. Blood cell formation and destruction in relation to the mechanism of thyroid accelerated metamorphoses in the larval frog. J. Exper. Med. 38:529.

and . 1923b. Studies on

lymphocytes. I. Effects of splenectomy, experimental hemorrhage and a hemolytic toxin in the frog. Am. J. Anat. 32:155.

Kampmeier, O. E. 1920. The changes of the systemic venous plan during development and the relation of the lymph hearts to them in Anura. Anat. Rec. 19:83.

Maximow, A. A. and Bloom, W. 1942. A Textbook of Histology. Saunders, Philadelphia.

McClure, C. F. W. 1921. The endothelial problem. Anat. Rec. 22:219.

Miller, A. M. 1903. The development of the postcaval vein in birds. Am. J. Anat. 2:283.

Minot, C. S. 1912. Chap. 18, Vol. II, p. 498, The origin of the angioblast and the development of the blood in Human Embryology by Keibel, F. and Mall, F. P. J. B. Lippincott Co., Philadelphia.

Noble, G. K. 1931. The Biology of the Amphibia. McGraw-Hill, New York and London.

Reagan, F. P. 1917. Experimental studies on the origin of vascular endothelium and of erythrocytes. Am. J. Anat. 21:39.

Sabin, F. R. 1912. Chap. 18, Vol. II, p. 709, Development of the lymphatic system in human embryology by Keibel, F. and Mall, F. P. J. B. Lippincott Co., Philadelphia.

Scammon, R. E. 1913. The development of the elasmobranch liver. Am. J. Anat. 14:333.

Stockard, C. R. 1915. The origin of blood and vascular endothelium in embryos without a circulation of the blood and in normal embryos. Am. J. Anat. 18:227.


Tke Excretory and Reproductive Systems

A. Introduction

1. Developmental relationships

2. Functions of the excretory and reproductive systems

3. Basic embryonic tissues which contribute to the urogenital structures

B. Development of the excretory system

1. General description

a. Types of kidneys formed during embryonic development

b. Types of nephrons or renal units produced in developing vertebrate embryos

2. Functional kidneys during embryonic development

a. Pronephros

b. Mesonephros

c. Metanephros and opisthonephros

3. Development and importance of the pronephric kidney

a. General considerations

b. Shark, Squalus acanthias

c. Frog

d. Chick

e. Mammal (human)

4. Development of the mesonephric kidney

a. Squalus acanthias

b. Frog

c. Chick

d. Mammal

5. Development of the metanephric kidney

a. Chick

1) Metanephric duct and metanephrogenous tissue

2) Formation of the metanephric renal units

b. Mammal (human)

1) Formation of the pelvis, calyces, collecting ducts, and nephric units

2) Formation of the capsule

3) Changes in position of the developing kidney

6. Urinary ducts and urinary bladders

a. Types of urinary ducts

b. Urinary bladders

c. Cloaca



C. Development of the reproductive system

1. Early developmental features; the indifferent gonad

2. Development of the testis

a. Mammal

b. Chick

c. Frog

3. Development of the ovary

a. Mammal

b. Chick

c. Frog

4. Development of the reproductive ducts

a. Male reproductive duct

b. Female reproductive duct

5 . Development of intromittent organs

6. Accessory reproductive glands in mammals

a. Prostate glands

b. Seminal vesicles

c. Bulbourethral glands

7. Peritoneal supports for the reproductive structures

a. Testis and ovary

b. Reproductive ducts

A. Introduction

1. Developmental Relationships

The excretory and reproductive systems often are grouped together as the urogenital system. This inclusive term is applied to these two systems because they are associated anatomically in the adult form and, during development, show marked interrelationships and dependencies.

An important relationship, shared by the developing reproductive and excretory systems, involves the caudal end or cloaca of the developing digestive tube. It is this area of the differentiating metenteron which affords an outlet to the external environment for the urogenital ducts in the majority of the vertebrate species. This fact will become obvious later.

2. Functions of the Excretory and Reproductive Systems

The functions of the reproductive systems of the male and female are discussed in Chapters 1 to 4 and 22.

The excretory system is most important in the maintenance of life, and is an important feature in the flow of fluids through the body as described in the introduction to Chapter 17. Food substances and water pass into the body through the walls of the digestive tract, and oxygen is admitted through the respiratory surfaces. The veins convey these substances to the heart and arteries (with the exception of fishes and some amphibia where oxygen passes directly into the arterial system), and the heart and arteries propel them to the tissues. Flere the food substances and water are utilized, and excess






CANAL mesonephric lUBULE


Fig. 344. Regions of kidney origin within the vertebrate group; types of renal units formed. (A) The regions in the body where the different types of vertebrate kidneys arise. The pronephric tubules and the pronephric duct are shown in black to emphasize the fact that this part of the developing renal system is a fundamental and necessary primordium without which later kidney development is distorted. (B) Differentiation of the anterior portion of the nephrotomic plate and the common method of origin of the pronephric duct. In the anterior region (toward the left in the figure) the nephrotomic plate segments into individual nephrotomes from each of which a renal tubule arises (see tubules 1 to 5). Tubules 6-9 is a vestigial area of tubule development. The anterior mesonephric region indicated by tubules 10 to 15, etc. In the anterior mesonephric area, e.g., tubules 10 and 11, the individual tubules show a tendency to arise segmentally, but in more posterior mesonephric regions, e.g., tubules 12 to 15, etc., the tubules arise through condensation of cellular masses within the nephrogenic cord. Hence, primitive

(Continued on facing page.)




salts, wastes, and water are the by-products. The veins, lymphatics, and arteries convey these substances to the areas of elimination as follows:

(1) Carbon dioxide and water are residues of carbohydrate metabolism. The carbon dioxide and some of the excess water in the body are discharged through the respiratory surfaces.

(2) The products of protein breakdown together with excess water and mineral salts are conveyed mainly to the kidneys and are eliminated there.

Exceptional areas exist for the elimination of some of the above-mentioned materials. For example, a certain amount of salts, nitrogenous wastes, and

Fig. 344 — (Continued)

segmentation is lost. The pronephric duct is formed through coalescence of the outer distal portions of the pronephric tubules (see tubules 3, 4, and 5). The coalesced portion thus formed grows caudally to join the cloaca. The mesonephric tubules, however, appropriate the pronephric duct in a secondary manner, growing outward to join this duct (see tubules 10 to 12). The pronephric duct, after this appropriation, becomes the mesonephric or Wolffian duct.

Figs. 344C-F are diagrams of different types of renal units (nephrons) which appear in developing vertebrate kidneys.

(C) This diagram represents a form of renal unit which we may designate as Type I. It is a vestigial tubule which may or may not become canalized. Its chief function is to initiate the formation of the pronephric duct. It is found in the pronephric kidneys of elasmobranch fishes, reptiles, birds, and mammals and, to some extent, in the anterior portion of the mesonephric kidneys of these groups.

(D) This diagram represents a renal unit found typically in the pronephric kidneys of larval forms such as that of the frog tadpole. It is designated as Type II. It possesses a ciliated nephrostome connecting with the coelomic cavity and a secretory portion which joins the pronephric duct.

(E) This diagram is given to represent the typical form of renal unit found in the earlier phases of mesonephric kidney development of lower vertebrates. It is called Type III. It is found also in the pronephric kidney of Hypogeophis (Gymnophiona) (see Brauer, ’02), With some modifications it may represent a type of renal unit found in the adult kidney of the urodele, Necturus maculosus (see fig. 345D).

(F) The Type IV renal unit is similar to Type III but lacks the ciliated nephrostomal connection with the coelomic cavity. It is the later renal unit of the mesonephric kidney of most fishes and amphibia and the typical renal unit found in the mesonephric kidney of reptile, bird, and mammalian embryos. With some elaboration it would represent the nephron (renal unit) found in the metanephric kidney of reptiles, birds, and mammals.

G.I., G.2., G.3., stages in development of the mesonephric tubule in the embryo of Squalus acanthias. G.l. and G.2. the tubule arises from the nephrotome in a segmental fashion and appropriates the pronephric duct. G.3. a later mesonephric tubule. In the latter tubule the nephrostomal connection with the coelomic cavity is lost. Observe that the tubule empties into the collecting duct, an outgrowth of the mesonephric duct. The early primitive segmental condition is lost and many tubules are formed in each body segment,



water pass off through the sweat glands of mammals; water and possibly small quantities of salts and wastes find riddance through the tongue’s surface and oral cavity of dogs; and the salt-excretory glands in the gills of teleost fishes remove excess salt materials from the blood, together with small amounts of nitrogenous substances. On the whole, however, the kidneys function to eliminate most of the nitrogenous residues and excess water, together with salt ions of various kinds, particularly those of chloride, sulfate, sodium, and potassium. The dispatch of salt ions by the kidneys is all important in maintaining the correct salt balance in the blood stream.

3. Basic Embryonic Tissues Which Contribute to the Urogenital Structures

The basic, embryonic, cellular areas which contribute to the formation of the excretory and reproductive structures are as follows:

(1) the nephrotomic plate (intermcdiatc-ccll-mass mesoderm) (fig. 344A).

(2) the adjacent coelomic tissue, underlying the nephrotomic plate during its development,

(3) the entodermal lining and surrounding mesoderm at the caudal end of the digestive tube, and

(4) the ectoderm of the integumentary areas where the urogenital openings occur.

(5) primordial germ cells.

B. Development of the Excretory System

1. General Description

The excretory system is composed of the following:

( 1 ) a series of excretory units, known as nephric units or nephrons,

(2) the kidney, a structure in which the nephrons are grouped together,

(3) a series of collecting ducts from a particular region of the kidney, which join the nephric units on the one hand and a main excretory duct on the other, and

(4) the cloaca (or its derivative, the urinary bladder) and a passageway to the external surface of the body (figs. 345A, B, D; 348G, D).

a. Types of Kidneys Formed During Embryonic Development

The kidney in Greek is called nephros and in Latin, ren. The words nephric and renal are adjectives, pertaining to the kidney but differing etymologically. By adding a prefix to the word nephros, various types of kidneys are denoted as follows:

(1 ) Holonephros is a word that was introduced by Price (1896) and designates a kidney derived from the entire nephrotomic plate in which a single nephron (nephric unit) arises from each nephrotome. (The



word nephrotome is applied to each segmented mass or bridge of mesoderm, developed within the nephrotomic plate, which connects the somite to the unsegmented lateral plate mesoderm or hypomere. See figure 344B.) The early development of the kidney tubules in the hagfish, Polistotrema (Bdellostoma) stouti (Price, 1896), and in the elasmobranch fish, Squaliis acanthias (Scammon, Tl), tends to simulate holonephric conditions.

(2) Pronephros, mesonephros, metanephros, and opisthonephros are terms for types of kidneys. Actually, during the development of all gnathostomous vertebrates, the nephrotomic plate on either side produces not one holonephros but instead three types of kidneys which are adapted to three different developmental and functional conditions. These kidneys develop antero-posteriorly in three general regions of the nephrotomic plate (fig. 344A). The most anteriorly developed kidney is called the pronephros; the kidney which develops from the midregion of the nephrotomic plate is the mesonephros; and that which arises from the caudal end of the nephrotomic material is the metanephros. Kerr (T9) attaches the name opisthonephros to the kidney which arises posterior to the pronephros in the late larvae of fishes and amphibia. The opisthonephric kidney takes its origin from the entire caudal portion of the nephrotomic plate. It therefore represents the nephrogenic tissue of the posterior part of the embryonic mesonephric kidney plus the nephrogenic material which enters into the formation of the metanephric kidney of reptiles, birds and mammals.

. b. Types of Nephrons or Renal Units Produced in Developing Vertebrate Embryos

Four main types of renal units are produced during kidney development in various vertebrate species. Consult figure 344C-F.

2. Functional Kidneys During Embryonic Development

During embryonic development, the following types of functional kidneys occur in the gnathostomous vertebrates.

a. Pronephros

The pronephric kidney is functional in all species producing free-living larval forms. In these larvae it operates not only to remove waste materials but is essential also in the removal of excess water, thus preventing edema (Howland, M6, ’21; Swingle, ’19). Free-living larvae are found in teleost, ganoid and lung-fishes, and in the amphibia.

b. Mesonephros

In all free-living larvae the pronephros is succeeded by the mesonephros during the larval period. The decline of the pronephros and the ascendancy



of the mesonephros is well illustrated in figure 335B-E relative to the developing venous system in anuran larvae. The mesonephric kidney also functions in the embryos of elasmobranch fishes, reptiles, birds, and mammals. In the mammals its efficiency as a renal orggn appears to be correlated with the degree of intimacy existing between the extra-embryonic and maternal tissues in the placenta. When this relationship is intimate (fig. 373D) as in rats, mice, humans, etc., the mesonephric kidneys are less developed, and therefore probably less functional, than in species such as the pig. In the pig the placental relationship between embryonic and maternal tissue is not so close as in the species mentioned above (fig. 373B), and the mesonephric kidneys are very large and well developed.

c. Metanephros and Opisthonephros

As indicated on p. 773 the metanephros is the kidney of the adult form of reptiles, birds, and mammals, while the opisthonephros is the mature kidney in fishes and amphibians. As the definitive or adult form of the body is achieved in both of these groups, the mature form of the kidney assumes the renal responsibilities.

3. Development and Importance of the Pronephric Kidney

a. General Considerations

Observation and experimentation upon the developing urinary and genital systems of gnathostomous vertebrates suggest that the pronephric kidney, and particularly its duct, the pronephric duct, are most important in the later development of the excretory and reproductive systems (Gruenwald, ’37, ’39, ’41). The pronephric kidney therefore may be regarded as fulfilling two important functions in the gnathostomous vertebrates, namely:

( 1 ) It operates as an early renal organ in free-living larval species, and

(2) It is a necessary precursor in the development of the reproductive system and the later excretory system.

The pronephric kidney develops from the anterior portion of the nephrotomic plate at about the level of the developing heart and stomach region (fig. 3 44 A and B). This area of the nephrotomic plate becomes segmented into separate nephrotomes (fig. 344 A and B). During the differentiation of each nephrotome in the pronephric area, the connection between the nephrotome and the dermo-myotome disappears, and a small dorso-lateral outgrowth from the middle portion of the nephrotome occurs (fig. 344B, 1 and 2). This cylindrical outgrowth proceeds dorso-laterally toward the developing skin and then turns posteriad and grows caudally (fig. 344B, 3). In the next posterior nephrotome, it meets a similar rudimentary tubule with which it unites (fig. 344B, 3 and 4). The area of union formed by these combined tubules



grows caudal ward to the next nephrotome to unite with its tubule (fig. 344B, 5), etc. As a result, the fused portions of the pronephric tubules give origin to the pronephric or segmental duct (fig. 344B).

The above method of origin of the pronephric duct has been described for elasmobranch fishes, reptiles, birds, and mammals. A different method of pronephric duct origin occurs in the amphibia and teleosts where the pronephric duct apparently arises by a longitudinal splitting of the nephrotomic plate (Field, 1891; Goodrich, ’30). The pronephric duct, once formed, continues to grow caudalward above the nephrotomic plate until it reaches the caudal end of the plate. In this area, the growing end of the pronephric duct turns ventrally and joins the cloaca (figs. 344A; 346F).

The entire pronephric portion of the nephrotomic plate is never realized in the formation of pronephric tubules. The number of tubules actually formed varies greatly and is confined generally to a limited number of nephrotomes in the middle or posterior pronephric are^

b. Shark, Squalus acanthias

In Squalus acanthias, a considerable nephrotomic area, overlying the caudal portion of the developing heart in segments 5-11, may produce suggestive indications of pronephric tubule formation. However, generally only three to five pronephric tubules are definitely formed. The distal ends of these tubules unite to form the pronephric or segmental duct and the latter grows caudalward to join the cloaca. The pronephric tubules are aberrant and soon disappear, but the pronephric duct remains and when joined by the mesonephric tubules it becomes known as the Wolffian or mesonephric duct (fig. 347A).

c. Frog

In the frog, Rana sylvatica, Field (1891) describes the origin of the pronephric kidney from a thickening and outgrowth of the somatopleuric layer of the nephrotomic plate in segments 2-4. Three tubules arise from this thickened area, one tubule in segment two, another in segment three, and a third in segment four.

A cross section of the developing second pronephric tubule at a time when the neural tube is wholly closed and a short while before hatching is shown in figure 346A. At about the time of hatching the second pronephric tubule is well advanced, as indicated in figure 346B, and the fully developed first pronephric tubule of an embryo (larva) of about 8 mm. is shown in figure 346C. The entire pronephric kidney of one side consisting of three tubules viewed from the ventral aspect at the 8 mm. stage is presented in figure 346E. The general plan of the pronephric kidney at the 18 mm. stage is pictured in figure 346F. Figure 346D lies in plane A-D of figure 346F.

Contrary to the manner of origin of the pronephric duct from the distal ends of the pronephric tubules in the embryo of Squalus acanthias, Field de



scribes the origin of this duct in the frog from a thickening of the somatopleuric layer of the nephrotomic plate in segments 4-9. This somatopleuric thickening separates, becomes canalized, and grows caudally to join the dorsal area of the cloaca, a union which is accomplished at about the time of hatching (fig. 25 8F'). The pronephric tubules in their development unite with the cephalic end of this duct.

As the development of the pronephric kidney advances it is to be observed that one large glomus is formed, projecting into the restricted coelomic chamber or nephrocoel which is shut off partly from the common peritoneal cavity by the expanding lungs (fig. 346D). Each ciliated nephrostome opens into this nephrocoelic chamber (fig. 346F). {Note: Reference may be made to figure 335A-C which shows the well-developed renal portal system inserted into postcardinal vein in relation to the pronephric kidney. The postcardinal vein breaks up into a series of small capillaries which ramify among the coiling pronephric tubules (see figure 346C) to be gathered up again into the posterior cardinal vein as it opens into the common cardinal vein.)

d. Chick

The pronephric tubules of the pronephric kidney of the chick are rudimentary, occupying a region of the nephrotomic plate, from the fifth to the sixteenth somites. However, all of the tubules do not appear simultaneously.

The pronephros begins to form at about the stage of 12 to 13 pairs of somites (stage 11, Hamburger and Hamilton, ’51, or at about 40 to 45 hrs. of incubation), and small aberrant tubules are formed (fig. 345E) which grow caudally to give origin to the pronephric duct as indicated in figure 344A.

Fig. 345. Developing kidney tubules. (A & B) General structure of adult human kidney. (A) This diagram represents a single renal unit in relation to blood vessels, collecting duct and the minor calyx. Arrows denote direction of excretional flow. The position of A in drawing B is shown by the elongated oblong in B. (A is redrawn, somewhat modified, from Glendening, 1930, The Human Body, Knopf, Inc., N. Y.) (B)

Human kidney, part of wall removed, exposing pelvis and other general structures. (Redrawn from Maximow and Bloom, 1942, A Textbook of Histology, Saunders, Philadelphia, after Brauer.) (C) Including C-1 to C-6. Stages in the development of a mesonephric renal unit in the frog, Rana sylvatica (C to C-6 redrawn from Hall, 1904, Bull. Mus. Comp. Zool. at Harvard College, vol. 45). C represents a section through a developing mesonephric tubule showing cellular condensation in relation to pronephric (mesonephric) duct. C-1 to C-6 are diagrammatic figures of a developing renal unit from right side of body. The somatic or lateral portion of the tubule is shaded by lines, the splanchnic portion is unshaded. (D) Diagrammatic representation of a section through pelvic kidney of Necturus maculosus. (Redrawn and modified from Chase, 1923, J. Morph., 37.) A tubule of the ventral series is shown with a peritoneal canal and ciliated nephrostome which opens into the coelomic cavity. A tubule of the dorsal series also is depicted. The latter type of tubule lacks a ciliated nephrostome opening into the coelom. (E) Pronephric tubule in the chick. Section passes through somite 11 of embryo of 16 17 somites. (F) Section through mesonephric kidney of 96 hr. chick embryo, partly schematized. (G) Schematized section through mesonephric kidney of six to seven day chick.





At the 16- to 21 -somite stage, the pronephric kidney is well developed, but not all the tubules are present. At the 21 -somite stage, pronephric tubules are present from the eleventh to fifteenth somites. Anterior to this area, they are degenerate and rudimentary. At the 3 5 -somite stage (65 to 70 hrs. of incubation or stage 18, Hamburger and Hamilton, ’51 ), the pronephric kidney as a whole is undergoing degeneration, although the pronephric duct (now the mesonephric duct) remains and, at this time, joins the dorso-lateral area of the cloaca.

e. Mammal (Human)

In the human embryo, the pronephric rudiments extend from the seventh to the fourteenth somites (fig. 344A), although rudimentary conditions may extend as far forward as segment 2 (Felix, ’12). The pronephric kidney appears in embryos of about 9 to 10 pairs of somites, and begins to degenerate at a stage of 23 to 28 segments. As in the chick and the shark, the pronephric duct arises from the fusion of the dorso-lateral ends of the rudimentary pronephric tubules and grows caudalward to open into the ventro-lateral aspect of the cloaca in embryos of 4.2 mm., greatest length (fig. 344A). (See Felix, ’12.)

Although the human pronephros is vestigial, it is as well developed as in any other mammalia.

/ 4. Development of the Mesonephric Kidney

The mesonephric kidney develops in the region of the nephrotomic plate posterior to the pronephric kidney (fig. 344A). Five features distinguish the mesonephric kidney from the pronephric kidney:

(1) The primitive segmentation manifest in the origin of the pronephric kidney tubules is lacking generally in the mesonephric kidney, although there is a tendency for the tubules to arise segmentally in the anterior region. Also, a segmental origin of the tubules throughout the length of the early mesonephros occurs in the embryo of the hagfish, Pollstrotrema (Bdellostoma) stouti (Price, 1896), and a primitive segmental condition is found in the early mesonephros of the shark and frog embryos as indicated below.

(2) The mesonephric tubules join the previously formed pronephric duct and thus appropriate this duct. The pronephric duct then becomes the mesonephric (Wolffian) duct.

(3) The antero-posterior extent of the mesonephric kidney is much greater than the pronephric kidney, the mesonephric kidney utilizing the greater part of the nephrotomic plate.

(4) An innovation, the collecting duct system, is introduced in the mesonephric kidney as a result of outgrowths from the mesonephric duct.





Fig. 346. The developing pronephric kidney in the frog, Rana sylvatica (A-C and E, redrawn from Field, 1891, Bull. Mus. Comp. Zool. at Harvard College, vol. 21. E considerably modified). (A) Transverse section through developing second pronephric tubule of frog embryo at a time when the neural tube is completely closed, two gill fundaments are present and the otic vesicle is a shallow depression. (B) Same tubule at about the time of hatching. (C) Section through first pronephric tubule at 8 mm. stage. (D) Transverse section through second pronephric tubule, see line d, fig. 346F, of 18 mm. Rana pipiens tadpole. (E) Entire pronephric kidney of one side of 8 mm. R. sylvatica embryo. (F) Schematic reconstruction of 18 mm. R. pipiens tadpole looking down from dorsal area upon the pronephric kidneys and the developing mesonephric kidneys.




The renal units empty their products into these collecting ducts in the mature form of the kidney.

(5) Whereas the functional pronephric kidney is confined to those species which develop free-living larvae, the mesonephric kidney is functional in all vertebrate embryos with the possible exception of a few mammalian species?)

a. Squalus acanthias

The mesonephric tubules in the embryo of Squalus acanthias and in other elasmobranch fishes originate in a manner similar to the pronephric tubules. That is, a single tubule arises from each nephrotome of the nephrotomic plate. In doing so, the nephrotome loses its connection with the developing somite or dermo-myotome, and its dorso-lateral aspect thickens and grows laterad in the form of a tubule. This tubule comes in contact, and fuses, with the pronephric or segmental duct (fig. 344B, 11; G.l, G.2). The latter then becomes the mesonephric or Wolffian duct. In the 20.6-mm. embryo of Squalus acanthias according to Scammon (’ll), 37 pairs of these tubules are present, extending along the mesonephric duct to the cloaca (fig. 347A). Later, this primitive segmentation is lost, and many tubules are developed in each segment. The anterior portion of the kidney soon degenerates; the nephrostomal connections of the mesonephric tubules with the coelom established during the development of the tubules are lost; and the mesonephric tubules assume the general morphology shown in figure 344G.3). As shown in figure 344G.3, a series of collecting ducts eventually develops to connect the mesonephric tubules with the mesonephric duct. Renal units eventually arise in the nephrogenous tissue overlying the cloaca. This area corresponds to the metanephric region of higher vertebrates, and the mature kidney of Squalus acanthias thus becomes a combination of caudal, mesonephric, renal units, associated with metanephric units. The mature kidney thus is an opisthonephros. (See Kerr, ’19, also p. 773). In the adult kidney, segmentally arranged nephrostomes may be observed in a limited area along the medial side of the kidney, although they do not connect with the renal units.

b. Frog

The mesonephric renal units in the frog begin to arise at about the 10-mm. stage. As in the shark embryo, the early origin of the mesonephric renal units is segmental. An intermediate zone of the nephrotomic plate between the developing mesonephros and the pronephric kidney does not develop renal units. Coincident with this fact those units which arise more posteriorly in the nephrotomic plate are developed better than those which arise anteriorly.

The renal units arise as cellular condensations of mesodermal cells within the cellular mass of the nephrotomic plate (fig. 345C-1). These cellular condensations elongate, become canalized, and assume a union with the meso



nephric duct as shown in figure 345C-1 to C-5. A nephrostomal connection with the coelomic cavity also appears, but the nephrostomal segment soon acquires a secondary connection with a renal vein (fig. 345C, 4-6). The veins thus come to drain the coelomic cavity directly. (In the water-abiding urodele, Nectiirus maculosus, the nephrostomal connection remains in contact with some of the renal units, even in the adult. See figure 345D.)

As the mesonephric kidney of the frog continues to develop, many new mesonephric renal units are added, and several units appear in each body segment. In consequence the primitive segmental arrangement of the renal units is lost, particularly in the caudal region of the nephrotomic plate where the kidney is developed most highly. Collecting ducts develop as evaginations of the mesonephric duct and the renal units discharge their contents into these collecting ducts.

Caudally situated nephrotomic material, comparable to the metanephric area of the kidney of higher vertebrates, is incorporated along with the mesonephric kidney as in the shark embryo. The adult form of the kidney, therefore, may be regarded as an opisthonephros, composed of mesonephric and metanephric renal units.

c. Chick

The mesonephros of the chick develops from the nephrotomic plate in the region between the somites 13 and 30. The nephrotomic plate in the chick embryo increases its substance rapidly through cell proliferation posterior to the area of pronephric-kidney origin. The original nephrotomic plate in this way becomes converted into an elongated mass or cord of cells called the nephrogenic cord. The mesonephric tubules arise as condensations within this cord of nephrogenous tissue. The renal unit emerges initially as a rounded mass of epithelial cells as in the frog. These epithelial masses elongate. They acquire a Malpighian body at one end, while the other end unites with the mesonephric duct. Some of the anterior tubules may have coelomic connections, similar to the pronephric tubules, but as this portion of the mesonephric kidney degenerates, these nephrostomal structures have little functional significance.

As development progresses, the nephrotomic substance increases greatly through proliferation of its constituent cells, and several renal units arise in each body segment (fig. 345F). To aid this process, the mesonephric duct forms collecting ducts which extend outward into the region of the developing renal units, and a group of these units joins each collecting duct (fig. 345G). The mature form of the mesonephric tubule of the chick consists of a glandular (secretory) segment which connects with either the mesonephric or the collecting duct on the one hand and with a Malpighian body and its glomerulus on the other (fig. 345G). The mesonephric kidney of the chick is a prominent ^^xcretory organ from the fifth to the eleventh day. During



the developmental period from 8 to 10 days its tubular system is exceedingly complex compared to that shown in figure 345G. After this period, it begins to degenerate, and its function is taken over by the developing metanephric kidney.

d. Mammal

As in the chick, the mesonephric kidney in many mammalian embryos is a prominent excretory structure. However, in the rat, mouse, and certain other mammals its function as an excretory organ is dubious, probably resulting from the fact that the placental connection in these forms is sufficiently intimate to assume excretory functions. In the 10-mm. pig (figs. 261, 262), it is a prominent structure, filling a considerable part of the coelomic cavity on either side. In the human embryo, the condition is intermediate between that of the pig and rat. It possibly functions as an excretory structure in the human embryo.

The renal unit or mesonephric tubule which is evolved within the nephrogenic cord is similar to that of the bird. It develops from a condensed mass of epithelium within the nephrotomic plate (nephrogenic cord). This condensed, S-shaped mass elongates, becomes canalized, and joins the mesonephric duct. The mesial end of the tubule, in the meantime, develops a Malpighian body with its glomerules and vascular connections. The glandular tube is a highly coiled affair and is associated intimately with the veins as indicated in figure 344F. Collecting ducts, arising as evaginations of the mesonephric duct similar to those in the chick mesonephros, are formed.

("5. Development of the Metanephric Kidney

The metanephric kidney is the later embryonic and adult form of the renal organ in reptiles, birds, and mammals. As observed above, the mesonephric kidney involves three structures:

( 1 ) the urinary or Wolffian duct,

(2) a series of collecting ducts which evaginate from the mesonephric or Wolffian duct to connect with the renal units, and

(3) the nephrons or renal units.

These same relationships are present in the developing metanephric kidney.

Fig. 347. Urogenital system relationships in various vertebrates. (A) Reconstruction of 20.6 mm. embryo of Squalus acanthias. (Redrawn from Scammon, 1911, Chap. 12, Normentafeln Entwichlungsgeschichte der Wirbeltiere, by F. Keibel, G. Fischer, Jena.)

(B) Left side view of dissection of male pickerel, Esox Indus, showing reproductive and urinary ducts and absence of a cloaca. (Redrawn from Goodrich, 1930, Studies on the Structure and Development of Vertebrates, Macmillan and Co., Limited, London.)

(C) Male reproductive system, ventral aspect, of the pigeon. (Redrawn from Parker, lonfi Zootomy, Macmillan and Co., Limited, London, The Macmillan Co., N. Y.)



a. Chick

1) Metanephric Duct and Metanephrogenous Tissue. The metanephric kidney in the chick begins to arise at the end of the fourth day of incubation from a diverticulum which evaginates from the caudal end of the mesonephric duct as the latter enters the cloaca (fig. 259). The origin of the metanephric diverticulum is similar to that of the various collecting ducts of the mesonephric kidney, i.e., it arises a's an outpushing from the mesonephric duct. The metanephric diverticulum enlarges as its distal end grows forward and dorsad into the nephrogenous tissue of the caudal end of the nephrotomic plate in trunk segments 31-33. As the metanephric diverticulum enlarges and grows into the nephrogenous tissue in this area, the nephrogenous tissue separates from the mesonephric tissue and, together with the metanephric diverticulum, moves anteriad above the mesonephros to the anterior end of the mesonephros. During this process, the distal end of the metanephric diverticulum enlarges into the future pelvic cavity of the kidney. Numerous small secondary evaginations make their appearance and extend outward from this cavity. The secondary evaginations from the primary pelvic cavity of the kidney form the rudiments of the future collecting ducts of the kidney.

2) Formation of the Metanephric Renal Units. The formation of the metanephric renal units is similar to that of the mesonephric units. At about 7 to 8 days of incubation, the nephrogenous tissue around the terminal ends of the collecting-duct evaginations from the primary pelvic cavity of the kidney forms dense epithelial masses. Each of these masses of condensed nephrogenous tissue assumes an S shape. One end of the S-shaped rudiment unites with the distal end of the developing collecting duct, while the other end forms a Malpighian body or renal corpuscle. (Comparable stages involving the development of the S-shaped rudiment in the mammalian metanephric kidney are shown in figure 348 A-C.) By the eleventh day, well-formed renal units are found in the developing kidney.

The outer capsule of the kidney arises from the peripheral portions of the nephrogenous tissue and surrounding mesenchyme. The metanephric kidney is retroperitoneal in position, that is, it lies outside the peritoneal cavity proper.

The posterior end of the metanephric duct or ureter acquires an independent opening into the cloaca as the above changes occur, for the caudal end of the mesonephric duct is drawn into, merges with, and thus contributes to the cloacal wall as the cloaca enlarges.

b. Mammal (Human)

1) Formation of the Pelvis, Calyces, Collecting Ducts, and Nephric Units.

As in the bird, the metanephric kidney of the mammal has a dual origin. One part, the metanephric diverticulum, arises as an evagination from the caudal end of the mesonephric duct at the level of the twenty-eighth somite in the 5- to 6-mm. human embryo (fig. 348H). This evagination extends dorsally

Fig. 348. The developing metanephric kidney. (A) Condensation of rudiment of renal tubule in relation to rudiment of arched collecting tubule. (B) Renal tubular rudiment has united with arched collecting tubule. (C) Later stage in differentiation of renal unit. (D) Final stage in development of renal unit. (E) Developing mesonephric and metanephric kidney of human embryo of about 5 weeks. (F & G) Mesonephric and metanephric conditions in human embryo of 8 mm. or about sixth week of development. (H) Diagram showing origin of metanephric uteric bud from caudal end of mesonephric duct in human embryo approximating 5.3 mm. greatest length. (Redrawn from Felix, 1912, in Chap. 19, Human Embryology, by F. Keibel and F. P. Mall, Lippincott, Philadelphia.) (I) Differentiation of kidney pelvis in human embryo of 20 mm. length or about seven weeks of gestation.




into the caudal end of the nephrotomic piate (nephrogenic cord). (See figure 348E.) The metanephric diverticulum enlarges at its distal end and thus forms the rudiment of the pelvis of the kidney as in the chick (fig. 348F). As the rudimentary pelvis enlarges, it sends out secondary evaginations, the rudiments of the future collecting ducts of the kidney (fig. 3481). Surrounding these secondary diverticula, there is the cellular substance (fig. 3481) of the metanephrogenous tissue, derived from the nephrogenic cord posterior to the caudal limits of the mesonephric kidney.

In human embryos of 14 to 15 mm. (about seven weeks), four definite primordia of the metanephric urinary system are established as follows (fig. 3481):

( 1 ) Nephrogenous tissue is present which surrounds beginning diverticula of the collecting ducts;

(2) a system of developing collecting ducts which represents evaginations from the primitive pelvis of the kidney;

(3) from the primitive pelvis of the kidney arise the rudiments of the anterior and posterior major calyces; and

(4) the primitive ureter (metanephric duct) of which the primitive pelvis is the distal enlargement.

(The word calyx refers to a rounded, distal division of the pelvis of the kidney. The plural form of calyx is calyces.)

From each major calyx, secondary or minor calyces arise (fig. 3481), and from each minor calyx, the primary or straight collecting ducts emerge into the surrounding, nephrogenous, cellular mass. Each primary calyx and its straight collecting-duct rudiments, together with the surrounding nephrogenous cells, form the rudiment of the future renal lobe.

The straight collecting ducts continue to elongate and push out into the surrounding nephrogenous tissue. In doing so, the distal end of each collecting duct sends out several (usually three or four) smaller evaginations into the surrounding nephrogenous material. These smaller terminal evaginations represent the rudiments of the arched collecting tubules of the collecting duct system (fig. 348A). Around each of the arched-tubule rudiments, masses of nephrogenous tissue condense into the S-shaped structure typical of the developing renal units of the mesonephric kidney of the frog, chick, and mammal and in the metanephric kidney of the chick. A sigmoid-shaped concentration of nephrogenous cells fuses with each arched collecting tubule and elongates distally, differentiating into the parts of the typical, mammalian, metanephric tubule (fig. 348A--D).

As the kidney continues to develop, the original primary or straight collecting ducts branch repeatedly, forming about 12 generations by the fifth month of human fetal existence. As these branches arise, the pelvis of the kidney and the calyces enlarge considerably, and some of the collecting ducts



are drawn into and are taken up into the walls of the expanding calyces. In the fully formed kidney, about 20 of these large straight collecting ducts open into the papillary ducts at the apex of the renal lobe or pyramid into a minor calyx (fig. 3 45 A, B) (Felix. ’12). The outer peripheral portion of the kidney, containing the glomeruli and various parts of the renal units (nephrons), forms the cortex of the kidney, while the inner portion, in which lie the straight collecting and papillary ducts, forms the medulla (fig. 345B).

2) Formation of the Capsule. The metanephrogenous tissue around the developing pelvis and collecting ducts of the kidney becomes divided into inner and outer zones. The inner zone cells differentiate into the renal units, whereas the outer zone cells form the interstitial connective tissue and outer, connective-tissue capsule of the kidney.

3) Changes in Position of the Developing Kidney. The early developing kidney is located in the pelvic area at the caudal end of the mesonephric kidney. As the mesonephric kidney declines in size and moves caudally, the metanephric kidney pushes anteriorly and takes its final retroperitoneal position at birth in the region of the first lumbar area. (Cf. figs. 3B-F; 348E-G.)

6. Urinary Ducts and Urinary Bladders a. Types of Urinary Ducts

The following two types of urinary ducts were mentioned above:

(1) The pronephric duct, which later becomes the mesonephric duct, is the functional urinary duct in the larval embryonic form of fishes, amphibia, reptiles, birds, and mammals. It continues to be the main urinary duct in adult fishes and amphibia, particularly in the female. (See (2) below.)

(2) A second type of urinary duct represents an outgrowth of the mesonephric duct. Examples of this type are: (a) the metanephric duct and its branches in the kidneys of reptiles, birds, and mammals, (b) the collecting ducts in the mesonephric kidney of all vertebrates, and (c) the adult urinary ducts in the posterior kidney region of certain male fishes, such as are present in the shark, Squalus acanthias, and in the salamander, Triton taeniatus.

b. Urinary Bladders

During the development of the urinary system in the mammal, the ventral portion of the cloacal area and its allantoic diverticulum become separated from the dorsal cloacal or rectal area by the caudal growth of a fold of tissue, known as the urorectal fold or cloacal septum. The cloacal septum eventually divides the cloaca into a ventral bladder and urogenital sinus region, and a dorsal primitive rectum (fig. 348E--G). As this development proceeds, the proximal portions of the mesonephric and metanephric ducts are taken up



into the wall of the caudal bladder region, and a considerable amount of mesoderm is contributed to the entodermal lining of the developing bladder. This mesodermal area presumably forms a part of the lining tissue of the bladder (fig. 349A, B). The metanephric duct or ureter, in the meantime, shifts its position anteriad and becomes united with the dorso-posterior portion of the bladder, while the point of entrance of the mesonephric duct migrates posteriad to empty into the anterior end of the dorsal region of the urogenital sinus (figs. 348F, G; 349A, B).

In turtles and in some lizards, the adult relationships of the urinary bladder and rectum are established in a somewhat similar manner to that of the mammals, although the caudal migration of the cloacal septum is not extensive. Also, the cloaca is retained.

The urinary bladder (or bladders) of some teleost and ganoid fishes arise as swellings and evaginations of the caudal ends of the mesonephric ducts (fig. 347B). A distinct urinary bladder is absent in elasmobranch fishes and in birds, but is present in amphibia as a ventral diverticulum of the cloaca.

c. Cloaca

A cloaca into which open the urogenital ducts and the intestine is a common basic condition of the vertebrate embryo. It is retained in the definitive or adult body form of elasmobranch fishes and to a considerable extent in dipnoan fishes. It is present also in the adults of amphibia, reptiles, birds (fig. 347C), and prototherian mammals. A cloaca is dispensed with in the adult stage of teleost (fig. 347B) and ganoid fishes, and also in the adult stage of higher mammals (fig. 349A-D).

C. Development of the Reproductive System

The general features of the adult condition of the reproductive system are described in Chapters 1 and 2. For most vertebrates, the reproductive system consists of the reproductive glands, the ovaries or testes, and the genital ducts.

Fig. 349. Differentiation of the caudal urogenital structures in the human embryo. (A) Later stage in differentiation of the cloaca; the rectal area is being separated from the ventrally placed urogenital sinus by the cloacal (urorectal) membrane. Condition of sixth week (about 12 mm.) embryo. (B) Rectal and urogenital areas completely separated. Mullerian and mesonephric ducts present. Metanephric duct has moved forward into the posterodorsal area of the developing bladder. The MUIlerian ducts have fused at their caudal ends to form the uterovaginal rudiment. This condition is present at about 8 weeks. (C) Male fetus of about 5 months. Testis beginning to pass into developing scrotal sac. (See also fig. 3.) (D) Female fetus of about 5 months.

(E to K) Stages in development of external genitalia. (E) Indifferent condition (about 7 weeks). (F) Male about tenth week. (G) Male about 3 months. (H) Male close of fetal life. (I) Female about tenth week. (J) Female about 3 months. (K) Female close of fetal life. (L & M) Stages in development of the broad ligament and separation of the recto-uterine pouch above from the vesico-uterine pouch below.

Fig. 349. (See facing page for legend.)

'-‘v;’, ’r'l-S},'




Fig. 350. Sex gland differentiation. (A) Transverse section through early genital rudiment on medial aspect of mesonephric kidney in the 10 mm. pig embryo. (B) Transverse section through early sex gland of the chick about middle of sixth day of incubation showing ingression of sex cord of first proliferation. Observe primordial germ cells in germinal epithelium. Compare with fig. 345G. (Redrawn from Swift, 1915, Am. J. Anat., 18.) (C) Transverse .section through sex gland rudiment of human embryo

11 mm. greatest length. (Redrawn and slightly modified from Felix, 1912, Chap. 19, in Human Embryology, vol. II, by F. Keibel and F. P. Mall, Lippincott, Philadelphia.) (D) Transverse section through testis of human embryo 70 mm. head-foot length. (Redrawn from Felix, 1912. For reference see C above.) (E) Section through human testis of embryo 70 mm. head-foot length, showing connection between te.sticular cords (developing .seminiferous tubules) and developing rete tubules. (Redrawn from Felix, 1912, reference same as in C, above.) (F) Transverse section through testis of seventh month human embryo showing developing seminiferous tubules. (Redrawn from Felix,

{Continued on facing page.)



1. Early Developmental Features; the Indifferent Gonad

The gonads or reproductive glands are associated intimately with the developing mesonephric kidneys. The typical site of origin is the area between the dorsal mesentery and the anterior portion of the mesonephric kidney (figs. 345F, G; 350C). As development progresses, it tends to move laterad and in doing so becomes located along the mesial aspect of the developing mesonephric ridge (figs. 3A; 345G).

The reproductive gland arises as an elongated fold, the genital ridge or genital fold. The extent of this fold, in general, is longer than the actual site from which the rudimentary gonad or reproductive gland arises, and it may extend for a considerable distance along the mesonephric kidney. Felix (’06) designates three general areas of the primitive genital ridge:

(1) a gonal portion, from which the sex gland arises,

(2) a progonal area in front of the gonal area, which gives origin to the anterior suspensory ligament of the gonad, and

(3) an epigonal area behind, which continues caudally as a peritoneal support along the mesonephric kidney (fig. 3A).

The rudimentary structural parts of the early genital ridge in the gonal area, viewed in transverse section, consist of the following (fig. 350A-C):

(1) primitive germ cells (origin of the germ cells discussed in Chapter 3, sec figure 60),

(2) the germinal (coelomic) epithelium and the primitive sex cords and cells proliferated therefrom, and

(3) contributions from mesonephric tissue, forming in most vertebrates the rete tissue of the urogenital union together with the primitive mesenchyme of the gonad.

The first stages in the development of the gonad consist of a thickening of the germinal (coelomic) epithelium and of a rapid and copious proliferation of cells from its inner surface. The primitive (primordial) germ cells become associated with the thickened germinal epithelium and its proliferated cells, and migrate inward into the substance of the gonad with the cells of the germinal epithelium (fig. 350B).

As a result of the activities of the germinal epithelium, a mass of cells, the

Fig. 350 — (Continued)

1912, reference same as in C, above.) (G) Differentiating testis in the wood frog, Rana sylvatica. (Redrawn from Witschi, 1931, Sex and Internal Secretions, edited by Allen et al., Williams and Wilkins, Baltimore.) (H) Ingrowth of sex cords from germinal epithelium of ovary of 6 weeks old rabbit. (Redrawn from Brambell, 1930, The Development of Sex in Vertebrates, Macmillan, N. Y.) (I) Section through differentiating

ovary in the opossum, 63 mm. pouch young. (J) Differentiating ovary in the wood frog, Rana sylvatica. (Redrawn from Witschi, 1931, reference same as G, above.)



so-called epithelial nucleus (Felix, ’12), is deposited in the genital ridge between the coelomic (germinal) epithelium and the Malpighian (renal) corpuscles of the mesonephric kidney (fig. 350C). As the epithelial nucleus increases in quantity, the genital ridge bulges outward from the general surface of the mesonephric kidney, and, at the same time, the nuclear cells push into the mesonephric substance against the renal corpuscles (figs. 345G; 350A-C).

During the early stages of the proliferative activities of the germinal epithelium in most vertebrates, cellular cords, the sex or medullary cords, appear to arise from the germinal epithelium (fig. 350B). These cords of cells are composed as indicated above of epithelial and germ cells. However, in the mouse and in the human, the proliferative activity of the germinal epithelium is such that the cellular nucleus of the genital ridge arises without a visible, dramatic ingrowth of cellular cords from the germinal epithelium (Brambell, ’27; Felix, ’12). Still, the cellular sex cords or elongated masses of cells do appear as secondary developments somewhat later in the genital ridges of the mouse and human (fig. 350C).

The early gonad up to this stage of development represents an indifferent, bipotential condition, having the structural basis for differentiation either into the testis or ovary (see figs. 350C; 351C-3). The indifferent condition in the human sex gland is present when the embryo is about 11 to 14 mm. long, i.e., at about the sixth or seventh week; in the chick, it occurs during the sixth day of incubation; and in the frog, it is present during the larval period.

2. Development of the Testis a. Mammal (Human)

As the indifferent gonad begins to differentiate into the testis, the following behavior is evident:

( 1 ) The germinal epithelium becomes a distinct flattened membrane, separated from the primitive tunica albuginea. Unlike the conditions in the developing ovary, the germinal epithelium quickly loses its germinative character and forms the relatively inactive, superficial membrane of the sex gland (fig. 350D). (The tunica albuginea eventually becomes a connective tissue layer below the coelomic (germinal) epithelium of the male and female sex glands.)

(2) The primitive sex or medullary cords of the indifferent gonad grow more pronounced, and they possibly may segregate lengthwise into separate, elongated cellular masses (fig. 350D).

(3) These elongated cellular masses or primitive seminiferous tubules become remodeled directly into the later seminiferous tubules. In doing so, their distal ends (i.e., the ends toward the primitive tunica albuginea of the sex gland) appear twisted and show anastomoses with neighboring seminiferous tubules, while their proximal ends assume



a straightened condition and project inward toward the area connecting the sex gland with the mesonephric kidney (fig. 350D).

(4) In the area between the inner ends of the developing seminiferous tubules and the Malpighian corpuscles of the mesonephric tubules, a condensation of cellular material occurs which forms the rete primordium (fig. 350D). From the rete primordium the future rete tubules are developed.

(5) As the rete tubules form, they unite with the inner straightened portions of the seminiferous tubules (the developing tubuli recti) and distally with the renal corpuscles (Malpighian bodies) of the mesonephric tubules (fig. 350E). The appropriated mesonephric tubules form to a considerable degree the efferent ductules of the epididymis.

(6) While the foregoing processes ensue, the sex gland gradually becomes separated as a body distinct from the mesonephric kidney and appears suspended from the kidney by a special peritoneal support, the mesorchium. Within the mesorchium are found blood vessels, lymphatics, and the efferent ductules of epididymis (fig. 350D).

(7) Coincident with these changes, mesenchyme between the developing seminiferous tubules forms a coating of connective tissue around each tubule. This connective tissue membrane gives origin to the basement membrane of the seminiferous tubule. Within the tubules, epithelial elements, primitive germ cells, and sustentacular elements (Chap. 3) or Sertoli cells appear. The Sertoli cells extend from the connectivetissue wall of the tubule inward between the epithelial and genitaloid cells. The genital cells lie close to the surrounding connective-tissue or basement membrane (figs. 8; 350F).

(8) Between the developing seminiferous tubules, the various cells, blood vessels, etc., of the interstitial tissue begin to appear (fig. 3 5 OF; see Chap. 1).

(9) Accompanying the foregoing transformations, the primitive tunica albuginea, which originally appeared as a narrow area, containing a few scattered cells between the germinal epithelium and the sex cords, becomes thickened and develops into a tough, connective-tissue layer, surrounding the testicular structures and separating the latter from the covering coelomic epithelium. This appearance of the tunica albuginea is one of the characteristic features of testicular development. Extending from the tunica albuginea inward between small groups of seminiferous tubules as far as the rete area or mediastinum, connectivetissue partitions are formed. These partitions are the septula. Each septulum comes to surround a small group of seminiferous tubules and thus divides the testis into compartments or lobules (fig. 7). Within each lobule, several seminiferous tubules are found, with the tubuli contorti or twisted portion of the tubules lying distally within



the compartment and the tubuli recti lying proximally toward the rete testis and mediastinum.

The formation of the rete-testis canals and of the urogenital union in general has been the subject of much controversy. In the elasmobranch fishes, Brachet (’21) considered the rete-testis canals to be formed by the nephrostomial canals of the anterior mesonephric tubules which unite with the developing seminiferous tubules. In the frog, Witschi (’21) believed a condensation of cells in the hilus of the testis formed the rudiments of the rete tubules and that these rudiments unite with the mediastinal ends of the seminiferous tubules on the one hand and with the renal corpuscles of the mesonephric tubules on the other, forming the urogenital union. In the chick, it is possible that the rete tubules arise as outgrowths from the renal corpuscles (Lillie, ’30, p. 394). In the human, Felix (’12) concluded that the rete tubules arise from a rete rudiment in the testicular hilus, but de Winiwarter (’10) considered them as outgrowths from the renal (Malpighian) corpuscles of the mesonephric tubules.

b. Chick

The development of the testis in the chick closely resembles that described above for the mammal. The sex or medullary cords arise during the fifth and sixth days of incubation from the germinal epithelium (fig. 350B). For a detailed description, consult Swift, ’16, and Lillie, ’30.

c. Frog

The main essentials of testicular development in the frog follow the pattern described above. However, because the gonadal rudiment of the frog differs slightly from that described for the mammal, certain features are presented here.

The germinal epithelium of the primitive gonad of the anuran is thin, and the primitive germ cells lie, together with various epithelial elements, below the germinal epithelium. In the center of this primitive gonad is the slit-like primitive gonadal cavity. This cavity is surrounded by the germ cells, epithelial cells and germinal epithelium. This condition may be regarded as the indifferent stage of gonadal development.

In the differentiation of the testis, cellular strands, the rudiments of the future rete tubules, grow down into the primitive gonadal cavity from the mesonephric kidney. In the male, these mesonephric strands are thick and grow rapidly. The primitive germ cells and epithelial cells eventually grow inward across the primitive gonadal cavity and become clustered about the mesonephric strands (fig. 350G).

At first the germ cells and epithelial elements form cellular nests associated with the mesonephric strands. Later, the cellular nests and associated cells from the mesonephric strands elongate into the primitive seminiferous tubules.



These seminiferous tubules develop lumina and unite directly with the rete tubules which arise, in the meantime, from cells of the mesonephric strands. The distal ends of the rete tubules join with the Malpighian corpuscles of certain mesonephric tubules. The mesonephric tubules thus united to the rete tubules are, of course, joined to the mesonephric duct. In consequence, these mesonephric tubules become the efferent ductules or vasa efferentia of the testis (Witschi, ’21, ’29).

3. Development of the Ovary a. Mammal

1) Formation of Primary Cortex and Medulla. The early phases of differentiation of the ovary varies in different mammalian species. Two features, however, are constant — features that serve to distinguish the differentiating ovary from the testis. One of these features consists of the fact that the ovary is more retarded in its development than the testis; the testicular features appear sooner in the male embryo than do ovarian features in the female embryo. This is a negative difference, but nevertheless, it serves to distinguish the two sexes. Another constant and positive feature, however, is that the germinal epithelium in the ovary retains its proliferative activity, while, in the differentiating testis, this activity is lost in the early stages of differentiation.

In the cat and rabbit (de Winiwarter, ’00, ’09 ), and in the calf and opossum, the first stage of ovarian differentiation is indicated by a second proliferation of sex cords (Pfluger’s cords) from the germinal epithelium (fig. 350H and I). The earlier sex or medullary cords thus are pushed inward toward the hilus of the* ovary, and a definite compact primary cortex is established, containing cords of epithelial and germ cells. The medullary cords become broken up in the meantime and are pressed inward in the direction of the forming primary medulla of the ovary. Some of the germ cells of the medullary cords undergo the earlier stages of meiosis but soon degenerate.

Synchronized with the foregoing changes in the peripheral area of the ovary are transformations within the hilar region, that is, the area of the ovary nearest to the mesonephric kidney. A conspicuous feature of these changes is the ingrowth of mesenchyme and differentiating connective tissue from the mesonephric kidney. Three morphogenetic phenomena accompany this ingrowth :

( 1 ) Blood vessels grow into the ovary from the mesonephric kidney to form a primitive vascular plexus within the developing medulla.

(2) A concentration of mesenchymal cells appears in the area between the developing ovary and the mesonephric kidney. This concentration of mesenchyme is the rete blastema, or the rudiment of the rete ovarii.

(3 ) From the region of the rete blastema radiating columns of mesenchyme and differentiating connective tissue fibers extend outward through



the medullary zone into the cortical zone of the ovary. These columns establish the septa ovarii. The septa ovarii branch distally, dividing the cortical zone into columns and compartmental areas of germ and epithelial cells.

The proliferation of sex cords (Pfluger’s cords) may continue from the germinal epithelium for an extensive period in certain mammals, such as the cat. De Winiwarter and Sainmont (’09) noted three successive periods, although Kingsbury (’38) was unable to find a clear-cut distinction between the first and second proliferation. In the developing opossum, active proliferation from the germinal epithelium may be observed up to a time just previous to the fourth month, following birth (Nelsen and Swain, ’42).

At an early stage of development, the primitive ovary in transverse section presents the following features (fig. 3501):

( 1 ) an outer proliferating germinal epithelium;

(2) a primitive tunica albuginea beneath the germinal epithelium, composed of epithelial and germ cells together with some connective tissue elements contributed by the ovarian septa;

(3) the primitive cortex, a compact layer within the primitive tunica albuginea, composed of masses of germ cells, egg cords, and epithelial elements, together with strands of differentiating mesenchymal cells. The mesenchymal strands from the ovarian septa segregate the egg cords into separate areas of germ cells and epithelial elements;

(4) internally, near the mesovarium or the peritoneal support of the ovary, is the primitive medulla composed of epithelial cells, mesenchyme, blood vessels, and some oocytes and oogonia;

(5) in the region of the mesovarium is a compact cellular mass, the rudiment of the rete ovarii, the homologue of the rudiment of rete testis in the male. The fundament of the rete ovarii continues rudimentary, but a framework of connective tissue is established in this area of the ovary similar to that of the mediastium in the testis, and

(6) from the area of the rete ovarii, radiating strands of mesenchymal cells, extend peripherally through the medulla and into the cortex, and thus establish the septa ovarii, i.e., septa of the ovary. Certain relatively large “interstitial cells” appear in the septula areas.

2) Formation of the secondary cortex and medulla. During later stages in ovarian development the following changes are effected:

( 1 ) The primitive tunica albuginea becomes converted into a relatively thick secondary tunica albuginea lying between the germinal epithelium and the cells of the cortical zone. It contains connective-tissue fibrils and fibers of larger dimension, together with mesenchyme and connective tissue cells. The changes in the developing tunica albuginea



are associated with an ingrowth of cells from the ovarian septa into the albuginean tunic.

(2) The primitive cortex transforms into a thick secondary cortex, containing many oocytes, some of which are surrounded by epithelial cells. The complex of an oocyte enclosed by epithelial cells forms a primitive egg follicle, which in mammals is called a primary Graafian follicle. The complete development of the Graafian follicle, however, does not occur until sexual maturity, although earlier stages may be produced previous to this period.

(3) A secondary medulla is formed containing a connective tissue network, enclosing blood vessels. From these blood vessels branches extend into the cortex. Some genitaloid cells may be found in the medulla.

(4) The rete blastema remains as a compact mass of cells, sharply delimited from surrounding cells. It comes to lie in the area between the ovary and the mesovarium, and forms the rete ovarii.

The development of the human ovary differs somewhat from the account given above in that active proliferation of cortical cords from the germinal epithelium is problematical. The proliferation of cells in the developing human ovary appears more gradual, and the egg cords of the primary cortex are developed in a gradual manner from cells lying below the germinal epithelium of the undifferentiated gonad (Felix, T2, p. 904).

b. Chick

The pattern of ovarian development in the chick follows that of the mammal, and a cortex and a medulla are established. One clear distinction in the ovarian development in the chick compared with that in the mammal occurs, however, for the right sex-gland rudiment remains vestigial in the chick while the left rudiment develops rapidly into the ovary. Thus it is, that sex differences can be distinguished in developing chicks by macroscopic examination of the sex glands during the latter part of the second week of incubation. The enlarged appearance of the left ovary in the female chick becomes noticeable at this time.

c. Frofi

The developing ovary in the frog differs primarily from the developing testis in two ways:

( 1 ) The germ cells and accompanying epithelial cells remain peripherally near the germinal epithelium, where they multiply and increase in number; some of them enlarge during the formative stages of the oocyte.

(2) The mesonephric rete cords, which in the testis are much thickened, appear slender in the developing ovary and fuse to form the lining


Fig. 351. Development of the reproductive and urinary ducts in vertebrates. (A-1 to A-4) Development of the reproductive ducts in Squalus acanthias. In A-2 the origin of the ostial funnel or coelomic opening of the oviduct is presented as a derivative of the opening of one or more pronephric tubules into the coelomic cavity. In fig. A-3, the urinary or opisthonephric duct is independent of the mesonephric (pronephric) duct which now is the vas deferens. The opisthonephric duct appears to take its origin as an evagination from the caudal end of the original pronephric duct. (B-1 to B-4) Development of the reproductive ducts in the frog. B-1 is adapted from data given by Hall, 1904, Bull. Mus. Comp. Zool. at Harvard College, vol. 45. (C-1 to C-7) Development

of the reproductive and urinary ducts in mammals. The MUllerian duct arises as an invagination of the coelomic epithelium at the anterior end of the mesonephric kidney. (See fig. 35 ID.) Once its formation is initiated, it grows caudalward along the pronephric

(Continued on facing page.)



tissue of the ovarian sac or enlarged space within the ovary (fig. 350J) . The ovary of the fully developed frog (and amphibian ovaries in general) is saccular (Chap. 2).

4. Development of the Reproductive Ducts

Most vertebrate embryos, with the exception of those of teleost and certain other fishes, develop two sets of ducts, one set of which later functions as reproductive ducts. These ducts are the mesonephric, Wolffian or male ducts and the Mullerian or female ducts. In the elasmobranch fishes, the Mullerian duct arises by a longitudinal division of the mesonephric duct (fig. 351 A). In the Amphibia, the Mullerian duct takes its origin independently. Anteriorly it arises as a peritoneal invagination of the coelomic epithelium, in the region of the cephalic end of the mesonephros. Posteriorly, this peritoneal invagination, as it grows caudally, appears to receive, in some urodeles, contributions from the mesonephric duct (fig. 35 IB). In the Amniota the Mullerian duct arises independently by a tubular invagination of the coelomic epithelium at the anterior end of the mesonephric kidney (fig.

Fig. 351 — (Continued)

(mesonephric) duct to join the cloaca (see fig. 351, C-2). The metanephric duct or ureter arises as an evagination of the caudal end of the pronephric (mesonephric) duct (see fig. 344A). C-2 is a drawing of the urogenital system of a 26 mm. pig embryo

viewed from the ventral aspect. Note extent of Mullerian duct growth caudalward. C-3 represents a generalized indifferent condition of the urogenital system of the mammal. C-4 and C-5 are diagrams of later stages in the development of the female (C-4) and the male (C-5), These conditions pertain particularly to human embryos. However, by a division of the uterus simplex into a bicornate or duplex condition it may be applied readily to other mammals. (C-6) Later arrangement of reproductive ducts and the associated ovaries in the human female after the descent of the ovaries. Observe origin of various ligaments. (In this connection see also fig. 3.) (C-7) Later development of

the reproductive duct-testis complex in the human male, during descent of the testis into the scrotum. Observe origin of testicular ligaments. (See also fig. 3.) (D) Transverse section through anterior end of the mesonephric kidney of 10 mm. pig embryo presenting the Mullerian duct invagination of the coelomic epithelium covering the mesonephros. E -N are diagrams showing the adult excretory and reproductive duct relationships in various fishes. The urinary ducts are shown in black. (Redrawn and modified from Goodrich, 1930, Studies on the Structure and Development of Vertebrates, Macmillan and Co., Limited, London, after various authors.)

It will be observed that in the male ganoid fish, Acipenser, the vasa efferentia extend from a longitudinal testis duct through the anterior or genital part of the kidney to the Wolffian (mesonephric) duct. The Wolffian duct thus becomes a duct of Leydig as in the frog. However, in teleosts, and in Protopteriis and Polypterus, a separate genital duct which opens into the caudal end of the mesonephric duct is evolved. Hence, the Wolffian (mesonephric) duct in these forms functions as a urinary duct only. The separation of the genital duct from the urinary duct, with the exception of the urogenital sinus region at the posterior end, is a fundamental characteristic of most vertebrate male reproductive systems, including many amphibia. In female fishes, fig. 351, 1-N, as in other vertebrates, the reproductive duct is always distinct from the urinary duct. The exact homologies of the reproductive duct in forms such as Lepisosteus (Lepidosteus) and teleosts (fig. 351, L-N) with the Mullerian duct in other verterbates is not clear.



TESTIS ligament Of\,






Fig. 351 — ( Continued)

See legend on pp. 798 and 799,



Fig. 351 — (Continued)

See legend on pp. 798 and 799.

35 1C). The blind caudal end of the invagination grows posteriorly along the side of the mesonephric duct to join the cloaca (fig. 351C-2).

a. Male Reproductive Duct

The developing gonad of the males of Amphibia, reptiles, birds, and mammals, together with the elasmobranch and ganoid fishes, appropriates the mesonephric duct for genital purposes. In this appropriation, the rete tubules of the testis unite with certain of the mesonephric tubules. The latter form the vasa efferentia or efferent ductules of the epididymis (fig. 351A-C). In teleosts, dipnoan fishes, and Polypterus, the marginal testicular duct becomes modified into a vas deferens which conveys the genital products to the urogenital sinus (fig. 351F-H).

In all vertebrates and in some mammals (Chap. 1), the testis remains within the abdominal cavity. However, in most mammals and in the flatfishes, there is a posterior descent of the testis (figs. 3 and 5) into a compartment posterior to the abdominal cavity proper.



b. Female Reproductive Duct

In the eutherian or placental mammals, the two Mullerian ducts in most species unite posteriorly to form a single uterovaginal complex (fig. 349B, D). In all other vertebrates, the Mullerian ducts or oviducts remain separate (see figures 33; 351A-4, B-4). The vagina of the eutherian female mammal probably is constructed partly of entoderm from urogenital sinus, for entoderm from this area invades the caudal end of the uterovaginal rudiment and lines the vaginal wall, at least in part (fig. 349B, D).

In the teleost fishes (fig. 35 IM, N), the origin of the Mullerian ducts is problematical (Goodrich, ’30, pp. 701-705).

5. Development of Intromittent Organs

Various types of intromittent structures are described in Chapter 4. The development of pelvic-fin modifications under the influence of the male sex hormone occurs in fishes. Cloacal intromittent structures are developed in certain Amphibia. A definite penis occurs in reptiles, certain birds, and in all mammals. The transformation, occurring in the external genital structures in male and female human embryos, is shown in figure 349E-K.

6. Accessory Reproductive Glands in Mammals

Refer to figures 2 and 349C.

a. Prostate Gland

The prostate gland arises as entodermal outgrowths from the membranous urethra near the entrance of the genital ducts. The surrounding mesenchyme provides the connective tissue and muscle. The paraurethral glands or ducts of Skene in the female represent minute homologues of the prostate gland.

b. Seminal Vesicles

The seminal vesicles arise as saccular outgrowths from the mesonephric ducts.

c. Bulbourethral Glands

The bulbourethral (Cowper’s) glands in the male arise as outgrowths from the entoderm of the cavernous urethra. The vestibular glands or glands of Bartholin are the female homologues of the bulbourethral glands.

7, Peritoneal Supports for the Reproductive Structures a. Testis and Ovary

The testis and ovary are pendent structures in all vertebrates and they are ’ ’ ■extensions from the dorso-lateral region of the



coelomic cavity. The support of the testis is the mesorchium and that of the ovary is the mesovarium. However, supports other than those mentioned in the preceding sentence are concerned with the support of the testis and ovary during development. Figures 3 A, B and 351C-3 demonstrate an anterior ligamentous, progonal support for the developing sex gland, whereas caudally there is a posterior, epigonal support continuing posterially to join the inguinal ligament of the mesonephros. In the developing mammal the progonal support merges with the diaphragmatic ligament of the mesonephros. Caudally the inguinal ligament of the mesonephros joins a ligamentous area in the genital swelling, known as the scrotal ligament in the male and the labial ligament in the female. Consult fig. 351C-6 and C-7 for later history.

b. Reproductive Ducts

The male reproductive duct (vas deferens, Wolffian duct) lies close to the kidney structures in the retroperitoneal space in most vertebrates other than those mammals with descended testes (see Chap. 1). The male reproductive duct, therefore, assumes a retroperitoneal position and is not suspended extensively within the coelomic cavity. On the other hand, the female reproductive duct (oviduct) is a pendant, twisted structure and is supported by a well-developed peritoneal support, the mesotubarium. In mammals, due to the fact that the reproductive ducts tend to join posteriorly, the mesotubarial supports, along the caudal region of the reproductive ducts, aid in dividing the pelvic region of the coelomic cavity into two general regions, viz., a dorsal or rectal recess, and a ventral, urinary recess (fig. 349L, M ).

In the mammals, the mesotubarial support of the Fallopian tube is known as the mesosalpinx. The mesosalpinx is continuous with the broad, shelf-like, lateral support of the uterus, known as the broad Ugament. The broad ligament is developed from the mesotubarium together with the remains of the mesonephric kidney substance (349L, M). The round Ugament of the mammalian uterus and the ovarian ligament arise from a basic rudiment comparable to the gubernaculum testis in the male (see figs. 3; 351C-3, C-6, C-7).


Brachet, A. 1921. Traite d’Embryologie des Vertebres. Paris.

Brambell, F. W. R. 1927. The development and morphology of the gonads of the mouse. Part I. The morphogenesis of the indifferent gonad and the ovary. Proc. Roy. Soc., London, sB. 101:391.

Brauer, A. 1902. Beitrage zur Kenntniss der Entwicklung und Anatomie der Gymnophionen. III. Die Entwicklung der Excretionsorgane. Zool. Jahrbiicher, Abt. Anatomie und Ontogenie. 16:1.

de Winiwarter, H. 1900. Recherches sur Povogenese et I’organogenese de I’ovaire des mammiferes (lapin et homme). Arch, biol., Paris. 17:33.

. 1910. Contribution a I’etude de

I’ovaire humain. Arch biol., Paris. 25:683.

and Sainmont, G. 1909. Nouvelles

recherches sur Povogenese et Porganogenese de Povaire des mammiferes (chat). Arch biol., Paris. 24:1.



Felix, W. 1906. Chap. 2, Part III, in Vergleichenden und Experimentellen Entwickelungslehre der Wirbeltiere by O. Hertwig. Gustav Fischer, Jena.

. 1912. Chap. 19 in Human Embryology by F. Keibel and F. P. Mall. J. B. Lippincott Co., Philadelphia.

Field, H. H. 1891. The development of the pronephros and segmental duct in Amphibia. Bull. Mus. Comp. Zool. at Harvard College. 21:201.

Goodrich, E. S. 1930. Studies on the Structure and Development of Vertebrates. Macmillan and Co., London.

Gruenwald, P. 1937. Zur Entwicklungsmechanik des urogenitalsystems beim Huhn. Arch. f. Entwicklngsmech. d. Organ. 136:786.

. 1939. The mechanism of kidney

development in human embryos as revealed by an early stage in the agenesis of the ureteric buds. Anat. Rec. 75:237.

. 1941. The relation of the growing Mullerian duct to the Wolffian duct and its importance for the genesis of malformations. Anat. Rec, 81:1.

Hamburger, V. and Hamilton, H. L. A series of normal stages in the development of the chick embryo. J. Morph. 88:49.

Howland, R. B. 1916. On the effect of removal of the pronephros of the amphibian embryo. Proc. Nat. Acad. Sc. 2:231.

. 1921. Experiments on the effect of

removal of the pronephros of Amblystoma punctatum. J. Exper. Zool. 32:355.

Kerr, J. G. 1919. Textbook of Embryology, Vol. II, Vertebrata with the Exception of Mammalia. Macmillan Co., Ltd., London.

Kingsbury, B. F. 1938. The postpartum formation of egg cells in the cat. J. Morphol. 63:397.

Lillie, F. R. 1930. The Development of the Chick. Henry Holt & Co., New York.

Nelsen, O. E. and Swain, E. 1942. The prepubertal origin of germ cells in the ovary of the opossum (Didelphys vir~ giniana). J. Morphol. 71:335.

Price, G. C. 1896. Development of the excretory organs of a myxinoid, Bdellostoma stouti Lochington. Zool. Jahrb. Anat. u. Ontogenic. 10:205.

Scammon, R. E. 1911. Normal plates of the development of Squalus acanthias. Chap. 12 in Normentafeln zur Entwicklungsgeschichte der Wirbeltiere von F. Keibel. G. Fischer, Jena.

Swift, C. H. 1916. Origin of the sex cords and definitive spermatogonia in the male chick. Am. J. Anat. 20:375.

Swingle, W. W. 1919. On the experimental production of edema by nephrectomy. J. Gen. Physiol. 1:509.

Witschi, E. 1921. Development of gonads and transformation of sex in the frog. Am. Nat. 55:529.

. 1929. Studies on sex differentiation and sex determination in amphibians. I. Development and sexual differentiation of the gonads of Rana sylvatka. J. Exper. Zool. 52:235.


Tke Nervous System

A. Introduction

1. Definition

2. Structural and functional features

a. The morphological and functional unit of the nervous system

b. The reflex arc

c. Structural divisions of the vertebrate nervous system

d. The supporting tissue

B. Basic developmental features

1. The embryonic origin of nervous tissues

2. The structural fundaments of the nervous system

a. The elongated hollow tube

b. The neural crest cells

c. Special sense placodes

3. The histogenesis of nervous tissue

a. The formation of neurons

1 ) General cytoplasmic changes - 2) Nuclear changes

3) Growth and development of nerve-cell processes

b. The development of the supporting tissue of the neural tube

c. Early histogenesis of the neural tube

d. Early histogenesis of the peripheral nervous system

C. Morphogenesis of the central nervous system

1. Development of the spinal cord

a. Internal changes in the cord

b. Enlargements of the spinal cord

c. Enveloping membranes of the cord

2. Development of the brain

a. The development of specialized areas and outgrowths of the brain

1 ) The formation of the five-part brain

2) The cavities of the primitive five-part brain and spinal cord

b. The formation of cervical and pontine flexures

c. Later development of the five-part brain

D. Development of the peripheral nervous system

1. Structural divisions of the peripheral nervous system

2. The cerebrospinal system

3. General structure and function of the spinal nerves

4. The origin, development and functions of the cranial nerves O. Terminal




I. Olfactory

II. Optic

III. Oculomotor

IV. Trochlear

V. Trigeminal

A. Ophthalmicus or deep profundus

B. M axillaris

C. Mandibularis

VI. Abducens

VII. Facial

VIII. Acoustic

IX. Glossopharyngeal

X. Vagus

XI. The spinal accessory

XII. Hypoglossal

5. The origin and development of the autonomic system

a. Definition of the autonomic nervous system

b. Divisions of the autonomic nervous system

c. Dual innervation of thoracicolumbar and craniosacral autonomic nerves

1) Autonomic efferent innervation of the eye

2) Autonomic efferent innervation of the heart

d. Ganglia of the autonomic system and their origin

E. The sense or receptor organs

1. Definition

2. Somatic sense organs

3. Visceral sense organs

4. The lateral-line system

5. The taste-bud system

6. The development of the olfactory organ

a. Development of the olfactory organs in Squalus acanthias

b. Development of the olfactory organs in the frog

c. Development of the olfactory organs in the chick

d. Development of the olfactory organs in the mammalian embryo

7. The eye

a. General structure of the eye

b. Development of the eye

c. Special aspects of eye development

1) The choroid fissure, hyaloid artery, pecten, etc.

2) The formation of the lens

3) The choroid and sclerotic coat of the eyeball; the cornea

4) Contributions of the pars caeca

5) The origin of the ciliary muscles

6) Accessory structures of the eye

8. Structure and development of the ear

a. Structure

1 ) Three semicircular canals

2) An endolymphatic duct

3) A cochlear duct or lagena

b. Development of the internal ear

c. Development of the middle ear

d. Development of the external auditory meatus and pinna

F. Nerve-fiber-effector organ relationships



A. Introduction

1. Definition

The nervous system serves to integrate the various parts of the animal into a functional whole, and also to relate the animal with its environment. It consequently is specialized to detect changes in the environment (irritability) and to conduct (transmit) the impulses aroused by the environmental change to distant parts of the organism. The environmental change provides the stimulus, the protoplasmic property of irritability detects the stimulus, and transmission of impulses thus aroused makes it possible for the animal to respond once the impulse reaches the responding mechanism. This series of events is illustrated well in less complex animal forms such as an ameba. In this organism, the stimulus aroused by an irritating environmental change is transmitted directly to other parts of the cell, and the ameba responds by a contraction of its protoplasm away from the source of irritation. On the other hand, the complex structure of the vertebrate animal necessitates an association of untold numbers of cells, some of which are specialized in the detection of stimuli, and others transmit impulses to a coordinating center, from whence still other cells convey the impulses to specialized effector (responding) structures (fig. 352A).

2. Structural and Functional Features a. The Morphological and Functional Unit of the Nervous System

There are two opposing views regarding the morphological and functional unit of the nervous system. One view, widely championed, postulates that this unit is a specialized cell called the neuron. The neuron is a distinct cellular entity, having a cell body containing a nucleus and a central mass of cytoplasm from which extend cytoplasmic processes of various lengths (fig. 352B). The nervous system is made up of many neurons in physiological contact with each other at specialized functional junctions known as the synapses (fig. 352A). The synapse represents an area of functional contact specialized in the conduction of impulses from one neuron to another. However, it is not an area of morphological fusion between neurons. Each neuron, according to this view, originates from a separate embryonic cell or neuroblast of ectodermal origin, and each develops a definite polarity, i.e. impulses normally pass in one direction to the cell body and from thence distad to the area of synapse.

A contrary, older view is the reticular or nerve-net theory. This theory assumes that the nerve cells and their processes are a continuous mass of protoplasm or syncytium in which the “cell bodies” are local aggregations of a nucleus and a cytoplasmic mass. The entire controversy between this and the neuron theory revolves around the “synapse area.” The neuron doctrine as



sumes a distinct morphological separation at the synapse, but the reticular theory postulates a direct morphological continuity. We shall assume that the neuron doctrine is correct.

b. The Reflex Arc

While the neuron, in a strict sense, represents the functional unit of the nervous system, in reality, chains of physiologically related neurons form the functional reflex mechanism of the vertebrate nervous system. The functional

Fig. 352. Neuron structure and relationships. (A) Structural components of a simple reflex arc. (B) Diagrammatic representation of a motor neuron. (Redrawn from Ranson, 1939, The Anatomy of the Nervous System, Philadelphia, Saunders, after Barker.) (C) Developing nerve fiber (process) of young neuroblast. Observe growth or incremental eone at distal end of growing process. (Redrawn from Ranson, 1939, The Anatomy of the Nervous System, Philadelphia, Saunders, after Cajal, Prentiss-Arey. ) (D) Neuron from spinal ganglion of a dog showing ganglion cell body with its surrounding capsular cells and capsule. Observe that the capsular cells and capsule are continuous with sheath cell and neurilemma. (Redrawn, somewhat modified, from Ranson, 1939, The Anatomy of the Nervous System, Philadelphia, Saunders.) (E) Longitudinal section of myelinated nerve fiber. (Redrawn from Ranson, 1939, The Anatomy of the Nervous System, Philadelphia, Saunders, after Nemiloff, MaximowBloom.)



reflex mechanism is an arrangement of neurons known as the reflex arc. Theoretically, a simple type of reflex arc would possess (fig. 352A):

( 1 ) a sense receiving structure, the receptor;

(2) the sensory neuron, whose long afferent or sensory fiber contacts the sensory receptor, while its efferent fiber or axon continues from the body of the neuron to the central nervous system. Within the central nervous system the terminal fibers (telodendria) of the efferent fiber of the sensory neuron forms a synapse with

( 3 ) the dendrites of an efferent neuron. From the efferent or motor neuron a motor fiber (axon) leaves the central nervous system and continues to

(4) the effector organ.

Functionally, however, even the simplest type of reflex arc may not be as elementary as this. More probably, a system of one or more association neurons placed between the sensory and motor neurons exists in most instances.

c. Structural Divisions of the Vertebrate Nervous System

The nervous system of vertebrate animals consists of

( 1 ) the central nervous system, a tubular structure composed of a coordinated assembly of association neurons and their processes. The central nervous system is integrated with

(2) the peripheral nervous system constructed of a series of sensory and motor neurons which connect the central nervous system with distal parts of the body. Through the medium of various types of sense receptors the central nervous system is made aware of changes in the external and internal environment of the body.

d. The Supporting Tissue

In addition to the irritable cellular neurons, the nervous system contains connective or supporting tissue. However, unlike most of the other organ systems of the body, the supporting tissue of the nervous system is derived mainly from an ectodermal source. Small amounts of connective tissue of mesodermal origin parallel the various blood capillaries which ramify through nervous tissue, but the chief supporting tissue of the brain and spinal cord is the neuroglia of ectodermal origin. The neuroglia consists of two main cellular types, the ependymal cells and the cells of the neuroglia proper.

The ependymal cells (fig. 353 A) form a single layer of columnar epithelium which lines the lumen of the neural tube. From the inner aspect or base of each ependymal cell a process extends peripherad toward the external surface of the neural tube (fig. 353F-H). Later the peripheral process may be lost. During the earlier stages of their development the ependymal cells are ciliated on the aspect facing the neurocoel (fig. 353A).



The cells of the neuroglia proper lie within the substance of the nerve tube between the neuron-cell bodies of the gray matter and also between the nerve fibers of the white matter (fig. 353H). Conspicuous among the neuroglia cells are the protoplasmic astrocytes (fig. 353D) which reside mainly among the neurons of the gray matter and the fibrous astrocytes (fig. 353B) found in the white matter. The processes of the fibrous astrocytes are longer and finer than those of the protoplasmic astrocytes, and they may attach to blood vessels (fig. 353B). Two other cellular types of neuroglia, the oligodendroglia and the microglia cells, also are present (fig. 353C and E). The microglia cells presumably are of mesodermal origin (Ranson, ’39, p. 57).

B. Basic Developmental Features

1. The Embryonic Origin of Nervous Tissues

The ectoderm of the late gastrula is composed of two general organ-forming areas, namely, neural plate and epidermal areas (fig. 192A). Both of these primitive ectodermal areas are concerned with the development of the future nervous system and associated sensory structures. From the neural plate region arises the primitive neural tube (Chap. 10), the basic rudiment of the central nervous system, whereas the line of union between the neural plate and the epidermal areas gives origin to the ganglionic or neural crest cells which contribute much to the formation of the peripheral nervous system. As observed in Chapters 9 and 10, the determination of the neural plate material and the formation of the neural tube are phenomena dependent upon the inductive powers of the underlying notochord and somitic mesoderm in the Amphibia. Presumably the same basic conditions obtain in other vertebrate embryos.

Fig. 353. Structure of the developing neural tube. (A) Ciliated ependymal cells from ependymal layer of the fourth ventricle of a cat. (Redrawn from Maximow and Bloom, 1942, A Textbook of Histology, Philadelphia, Saunders, after Rubaschkin.) (B-E) Various types of neuroglia cells. (Redrawn from Ranson, 1939, The Anatomy of the Nervous System, Philadelphia, Saunders, after Rio Hortega.) (F) Transverse section of neural tube of three-day chick embryo. The spongioblasts are stained black after the method of Golgi. (Redrawn from Maximow and Bloom, 1942. See reference under A, after Cajal.) (G) Transverse section of part of spinal cord of 15 mm. pig embryo showing structural details. This section was constructed from several sections. The part of the section to the left reveals the neuroglial support of the developing neuroblasts. (Redrawn from Hardesty, 1904, Am. J. Anat., 3.) (H) Transverse sec tion, constructed from sections, of part of the spinal cord of 55 mm. pig embryo showing neuroglial support for developing neuron cells. (Redrawn from Hardesty, 1904, Am. J. Anat., 3.) (I) Transverse section of spinal cord of newborn mouse depicting

spongioblasts which are moving peripherally from the central canal. These spongioblasts are in the process of transforming into stellate neuroglia cells or astrocytes. (J) Transverse section of 9 mm. pig embryo portraying ependymal, mantle, and marginal layers, external and internal limiting membranes, and blood vessels growing into the nerve substance. (Redrawn from Hardesty, 1904, Am. J. Anat., 3.) (K) Transverse

section of spinal cord of 20 mm. opossum embryo indicating general structure of the spinal cord. Observe dorsal root of spinal nerve growing into nerve cord at the right of the section.

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2. The Structural Fundaments of the Nervous System

The early nervous system shortly after the neural tube is formed is composed of an elongated, hollow tube, aggregations of neural crest cells, and a series of sense placodes.

a. The Elongated Hollow Tube

The primitive neural tube, located dorsally in the median plane (fig. 217G and H), forms the basis for the central nervous system and potentially is composed of two major regions, namely, the future brain region at its anterior end and posteriorly the rudiment of the spinal cord. The future brain region quickly develops three regions, viz.:

( 1 ) the prosencephalon, or the rudiment of the forebrain;

(2) the mesencephalon, or future mid-brain region, and

(3) the rhombencephalon, or hindbrain region (fig. 354D and E).

The rhombencephalon passes imperceptibly into the developing spinal cord, or the primitive neural tube posterior to the brain region.

The cephalic end of the primitive neural tube from the time of its formation tends to present a primary neural flexure, the cephalic flexure (see Chap. 10). This flexure occurs in the region of the mesencephalon. It is slight in teleost fishes, more marked in amphibia, and pronounced in elasmobranch fishes, reptiles, birds and mammals (fig. 354E and F).

During the early stages of neural tube development, the anterior end of the tube tends to form primitive segments or neuromeres. These neuromeres fuse together as they contribute to the primitive brain regions as indicated in figure 354A-D (see Hill, 1900).

b. The Neural Crest Cells

As the neural tube is formed, the neural crest cells come to lie along the dorso-lateral aspect of the neural tube. The crest cells soon become aggregated together in clumps, each aggregation representing the initial stage in the formation of the various cranial and spinal ganglia (see figures 347A; 357B-F).

c. Special Sense Placodes

The special sense placodes are a series of epithelial thickenings of the lateral portions of the epidermal tube overlying the future head region. These placodes, which represent contributions of the epidermal tube to the forming nervous system, are as follows:

( 1 ) The nasal placodes, two in number, each arising on either side of the ventro-anterior region of the primitive head.

(2) The lens placodes, two in number, each arising in relation to the optic outpushing of the diencephalic portion of the forebrain.



Fig. 354. Early development of the brain in the chick and teleost fish showing the tendency to form neural segments or neuromeres. (All figures redrawn from Hill, 1900, Zool. Jahrblicher, abt. Anat. u. Ontogenie 13.) (A) Dorsal view of developing brain of

chick embryo of 4 pairs of somites. (B) Dorsal view of primitive brain or encephalon of chick embryo of 7 pairs of somites. (C) Dorsal view of brain of chick embryo with 11 jpairs of somites. (D) Dorsal view of developing brain of chick embryo with 14 pairs of somites. (E) Lateral view of brain of chick embryo about 75 to 80 hours of incubation. In the foregoing illustrations, observe that the neuromeres gradually fuse to form parts of primitive five-part brain shown in E. (F) Brain, lateral view, Salmo fario, 33 somites, 22 days old. Segments 1-3 represent the prosencephalon, 4 and 5 the mesencephalon, 6 the anterior part of the rhombencephalon, and 7-11 to the posterior region of the rhombencephalon. Observe that the cephalic flexure is present slightly at this time. A little later in the 36 day embryo it is more pronounced.

(3) The acoustic placodes, two in number, taking their origin from the dorso-lateral portion of the epidermal tube overlying the middle portion of the hindbrain.

In water-dwelling vertebrates, other placodes arise in the head region associated with the lateral-line system. The lateral line placodes probably represent an extension of the acoustic placodal system in lower vertebrates. Hence, the general term acoustico-lateral or neuromast system (see Goodrich, ’30, p. 732) may be applied to this general system of sensory structures.

(4) Taste-bud placodes. The taste buds are distributed variously in different vertebrate species. In man, cat and in other mammals they are located on the tongue, particularly its posterior part (fig. 285E) on the



soft palate, and in the pharyngeal area. In fishes, taste buds are found generally over the buccal cavity and pharynx, and also on the outer surface of the head and branchial region. In some teleosts they may be distributed generally over the external surface of the body (fig. 356C). The external distribution of taste buds over the head region occurs also in certain aquatic amphibia. Consequently, the distribution of the epithelial thickenings which give origin to the taste buds varies greatly in different vertebrates.

3. The Histogenesis of Nervous Tissue a. The Formation of Neurons

The neurons of the central nerve tube arise from primitive neuroblasts. The primitive neuroblasts in turn take their origin from the cells of the ependymal zone of the nerve tube. The ependymal zone is the layer, two to three cells in thickness, which lines the lumen or neurocoel of the developing tube. Cell proliferation occurs within this zone, and the primitive neuroblasts migrate outward into the more lateral areas. After leaving the immediate confines of the ependymal zone, the neuroblasts presumably begin to differentiate into the many peculiar forms of the neurons to be found within the central nervous system. The neurons of the peripheral nervous system arise from cells which migrate from the central nerve tube, and from cells of the neural crests and certain sense placodes.

1) General Cytoplasmic Changes. The basic physiological functions of irritability and conductivity found in living protoplasm is developed to a high degree in the neuron or essential cellular entity of the nervous system. In consequence, the morphological changes which the simple epithelial cell of the forming neural tube assumes during its differentiation into a neuron is in harmony with these basic functions. One of the morphological changes in the developing neuroblast is the formation of coagulated threads of cytoplasmic material embedded in a more liquid cytoplasm. These threads arc known as neurofibrils, while the more liquid, less-differentiated parts of the cytoplasm are called the neuroplasm. Accompanying the changes which produce the neurofibrils is the formation of another characteristic of neurons, namely, processes or cytoplasmic extensions from the body of the cell (fig. 352B). These processes are of two general types, the dendrites and the axon (neuraxis or axis cylinder). Several dendrites are generally present but only one axon is developed. The exact function of the dendrites has been questioned but the possibility is conceded that they function as “the chief receptive organelles of the neuron” (Maximow and Bloom, ’42, p. 190), whereas the axon is believed to convey the nerve impulse away from the cell body to the terminal arborizations or teledendria (fig. 352A). The teledendria make physiologic contact (i.e., they synapse) with the dendrites of other neurons or they form a specialized relationship with effector cells such as glandular cells or



muscle fibers (fig. 352A). The neurofibrils extend into the cell processes. The precise relationship of the neurofibrils to conduction and transmission of nervous impulses is unknown. {Note: The formation of the sheaths surrounding the nerve fiber is described on page 819.)

2) Nuclear Changes. Associated with the changes in the cytoplasm mentioned above are alterations of the nucleus. One of the striking features of nuclear change is that it enlarges, and becomes vesicular, though the basichromatin remains small in quantity. The nucleolus experiences profound changes, and is converted from a homogeneously staining body into a vacuolated structure in which the desoxyribose nucleic acid is irregularly localized along the edges. Contemporaneous with the nucleolar changes there is a ‘‘marked production of Nissl substance in the cytoplasm” (Lavelle, ’51, p. 466), Accompanying the changes in the nucleus is its loss of mitotic activity, although a centrosome is present in the cytoplasm. All neuroblasts, however, do not lose their power of division; only those which start to differentiate into neurons. During embryonic life many potential neurons remain in the neuroblast stage and these continue to proliferate and give origin to other neuroblasts. Shortly after birth or hatching this proliferative activity apparently ceases, and the undifferentiated ncuroblasts then proceed to differentiate into neurons.

3) Growth and Development of Nerve-cell Processes. The early neuroblasts of the central nerve tube are at first apolar, that is, that do not have distinct processes. These apolar cells presumably transform in unipolar and bipolar varieties of neuroblasts. The unipolar cells have one main process, the axon, and the bipolar cells have two processes, an axon and a dendrite. From these two primitive cell types multipolar neurons arise having several dendrites and one axon (fig. 352B).

As the nerve-cell process begins to develop, a small cytoplasmic extension from the cell body occurs. To quote directly from Harrison (’07), p. 118, who was the first to study growing nerve -cell processes in the living cell: “These observations show beyond question that the nerve fiber develops by the outflowing of protoplasm from the central cells. This protoplasm retains its amoeboid activity at its distal end, the result being that it is drawn out into a long thread which becomes the axis cylinder. No other cells or living structures take part in the process. The development of the nerve fiber is thus brought about by means of one of the very primitive properties of living protoplasm, amoeboid movement, which, though probably common to some extent to all cells of the embryo, is especially accentuated in the nerve cells at this period of development.” The distal end of a growing nerve fiber has a slight enlargement, the “growth cone” or “growth club” (fig. 352C). The conclusions of Harrison on growing nerve fibers in tissue culture were substantiated by Speidel (’33) in his observations of growing nerve fibers in the tadpole’s tail.

Many different shapes of cells are produced during the histogenesis of the



neural tube. However, two main morphological types of cells may be considered :

( 1 ) One type of neuron possesses a short axon or axis cylinder. This type of neuron lies entirely within the gray substance of the neural tube.

(2) In a second type of neuron a long fiber or axis cylinder is developed and this fiber leaves the gray substance and traverses along the white substance of the cord or within the fiber tracts of the forming brain. In many instances, the cell body of the second type of neuron lies within the gray matter of the spinal cord, but its axis cylinder passes out of the nerve tube as the efferent or motor fiber of a spinal or cranial nerve (fig. 355F and I).

b. The Development of the Supporting Tissue of the Neural Tube

The potential connective tissue cell of the neural tube is the spongioblast. Spongioblasts are of ectodermal origin and differentiate into two main types of cells: (1) Ependymal cells, and (2) neuroglia cells.

Spongioblasts together with primitive neuroblasts lie at first within the ependymal zone of the neural canal particularly close to the lumen. Cilia are developed on the free surface of each spongioblast lining the neurocoel. From the opposite end of the cell, that is, the end facing the periphery of the tube, an elongated process extends peripherad to the outer surface of the neural tube. In this way a slender framework of fibers extends radially across the neural tube, from the lumen to the periphery (fig. 353F~K). A spongioblast which retains a relationship with the lumen and at the same time possesses a fiber extending peripherad is known as an ependymal cell. The ependymal cells thus are those cells whose bodies and nuclei lie next to the lumen of the developing spinal cord and brain but possess processes which radiate outward toward the periphery of the cord (fig. 3 53 A and F). The peripheral fiber or extension may be lost in the later ependymal cell together with its cilia.

In fishes and amphibians the supporting elements of the central nerve tube retain the primitive arrangement outlined above (see Ariens-Kappers, ’36, p. 46). However, in reptiles, birds and mammals, the radial pattern of many of the primitive spongioblasts is lost, and these spongioblasts transform into neuroglia cells, losing their connection with the lumen and with the external limiting membrane of the tube (fig. 3531).

c. Early Histogenetic Zones of the Neural Tube

The neural plate of the late gastrula is a thickened area of cells of about 3 to 4 cells in thickness. As the neural plate is transformed into the neural tube the majority of the neural plate cells become aggregated within the lateral walls of the tube. The lateral walls of the developing neural tube in consequence are thicker than the dorsal and ventral regions. As already observed



in Chapter 10, this discrepancy in the thickness of the walls of the tube is due (in the amphibia) to the inductive influence of the somite which comes to lie along the lateral regions of the primitive tube. In the 9-mm. pig embryo, the neural tube in transverse section begins to present three general zones (fig. 353J), viz.:

(1) an ependymal layer of columnar cells lining the lumen,

(2) a relatively thick nucleated mantle layer occupying the middle zone of the neural tube, and

(3) a marginal layer without nuclei extending along the lateral margins of the tube.

The ependymal layer of cells lies against the internal limiting membrane of the tube, and consists of differentiating spongioblasts as indicated above. The mantle layer contains many neuroblasts and in consequence is referred to as the middle nucleated zone. It forms the future gray matter of the neural tube. The outer or marginal zone in its earlier phases of development is a meshwork of neuroglia and ependymal cell processes. Later, however, the processes of neurons come to lie among the fibrous processes of the neuroglia and ependymal cells as the nerve cell fibers extend along the spinal cord. The external limiting membrane lies around the outer edge of the marginal layer, and thus forms the outer boundary of the tube. In figure 353H is shown the relationships of the ependymal, mantle and marginal layers of the spinal cord of a 55-mm. pig embryo together with the ependymal and neuroglia cells. The arrangement of the ependymal, mantle and marginal layers in the spinal cord of a 22-mm. opossum embryo is shown in figure 35 3K.

d. Early Histogenesis of the Peripheral Nervous System

The formation of the cerebrospinal scries of nerves which comprise the peripheral nervous system involves cells located within the neural crest materials and also within the mantle layer (gray matter) of the neural tube. One feature of the development of the spinal nerves is their basic metamerism, for a pair of spinal nerves innervates the somites of each primitive segment or metamere.

The neuroblasts of each spinal nerve arise in two areas, viz.:

(1) the neural crest material which forms segmental masses along the lateral sides of the neural tube, and

(2) cells within the ventral portions of the gray matter of the tube.

In the development of a spinal nerve bipolar neuroblasts appear within the neural crest material. Each bipolar neuroblast sends a process distad toward the dorso-lateral portion of the neural tube and a second process lateroventrad toward the body wall tissues, or toward the viscera. Later these bipolar elements become unipolar and form the dorsal root ganglion cells.



Fig. 355. Development of general structural features of the spinal cord; the nuclei of origin and nuclei of termination of cranial nerves associated with the myelencephalon. (A-E) The formation of the central canal, dorsal median septum, dorsal median sulcus, and ventral median fissure in pig embryos. Arrows in the dorsal part of the developing nerve cord show obliteration of the dorsal part of the primary neurocoel by medial growth of the lateral walls of the spinal cord. By this expansive, medial growth, the dorsal median septum and the dorsal sulcus (fissure) are formed. Observe that the central canal is developed from the ventral remains of the primary neurocoel after the obliteration of the dorsal portion of the primary neurocoel has been effected. In diagrams C-E, the




Within the ventral gray matter of the spinal cord, fusiform bipolar cells arise which send processes at intervals out into the marginal layers and from thence outward through the external limiting membrane of the tube at the levels corresponding to the developing dorsal root ganglia. The groups of processes which thus emerge from the neural tube below a single dorsal root ganglion soon unite with the ventrolateral processes of the dorsal root ganglion cells to form the ventral root of the spinal nerve. Within the neural tube the cell bodies of the ventral root fibers soon form multipolar neuron cells.

As development proceeds, the cell bodies of the neurons within the dorsal root ganglia become encased by capsular cells which develop from some of the neural crest cells (fig. 352D). The capsular cells in consequence are of ectodermal origin and they are continuous with the neurilemma sheath. The cells of the neurilemma sheath also arise from certain neural crest cells and from cells within the neural tube. These cells migrate distad as sheath cells along with the growing nerve fiber. The neurilemma or sheath of Schwann arises as an outward growth from the cytoplasm of the sheath cells; the neurilemma sheath thus appears in the form of a delicate tube surrounding the nerve fiber (axis cylinder) of the neuron (352D). Later on, a secondary substance appears between the nerve fiber (axis cylinder) and the neurilemma in many nerve fibers. This substance is of a fatty nature and forms the myelin (medullary) sheath (fig. 352E). Myelin deposition by sheath cells depends primarily upon an axis cylinder stimulus and not upon the sheath cells, for it is only a particular type of nerve fiber, the myelin-emergent fiber, which possesses the ability to form myelin (Speidel, ’33). In the peripheral nerve fibers, the neurilemma at certain intervals dips inward toward the axis cylinder, forming the node of Ranvier. The area between two nodes is known as an internodal segment (fig. 352B). One sheath cell is present in each internodal segment. The nerve fibers of the peripheral nervous system with respect to

Fig. 355 — Continued

arrows drawn in the ventral portions of the nerve tube indicate the ventro-medial expansion of lateral portions of the developing nerve tube with the subsequent formation of the ventral median fissure. In E the dorsal, ventral, and lateral columns or funiculi of white matter are shown. (F) Diagram depicting some of the principal fiber tracts of the spinal cord of man. Ascending tracts on the right; descending tracts on the left. (Redrawn from Ranson, 1939. For reference see G.) (G) Ventral view of human

spinal cord, nerves removed, showing cervical and lumbar enlargements. (Redrawn from Ranson, 1939, The Anatomy of the Nervous System, Philadelphia, Saunders.) (H) Diagram revealing the relation of the meninges, i.e., the protective membranes of the central nervous system, to the spinal cord. (Redrawn from Ranson, 1939. For reference see G.) (I) Schematic diagram of transverse section through myelencephalon (medulla),

portraying dorso-ventral position of nuclei of origin in motor plate and the nuclei of termination in alar plate of cranial nerves associated with the myelencephalon.



their sheath-like coverings are of two kinds, viz., myelinated fibers with neurilemma and unmyelinated (Remak’s) fibers with a thin neurilemma. The latter are found especially among the sympathetic nerve fibers of the cerebrospinal series. (See Ranson, ’39, p. 51.)

It may be observed here, parenthetically, that the myelinated fibers of the brain and spinal cord differ from the myelinated fibers of the peripheral nervous system in that the sheaths are formed by an investment of neuroglia fibers and nuclei and not by a neurilemma sheath. Many naked axons also are present in the central nervous system.

C. Morphogenesis of the Central Nervous System

1. Development of the Spinal Cord a. Internal Changes in the Cord

During the early development of the spinal cord described above the following areas are evident:

( 1 ) the ependymal layer,

(2) the mantle layer, and

(3) the marginal layer.

The further development of these areas results in the formation of a thin dorsal roof plate and a ventral floor plate mainly from the ependymal layer (fig. 353J and K), Somewhat later the neural cavity of the cord is reduced by the apposition and fusion of the dorso-lateral walls of the lumen immediately under the dorsal plate, leaving a rounded central canal below located near the floor plate (fig. 355A-E). Synchronized with these events the lateral walls of the neural tube expand greatly as the mass of cells and fibers increases. During this expansion, the two dorsal parts of the lateral walls move dorsad and mediad and in this way come to lie apposed together in the median plane above the central canal. This apposition forms the dorsal median septum (fig. 355D and E). The dorsal roof plate becomes obliterated during this process. Ventrally, also, the lateral portions of the neural tube move toward the mid-ventral line below the central canal. However, the two sides do not become closely apposed, and as a result the ventral median Assure is formed (fig. 355D andE).

During the growth and expansion of the two lateral walls of the neural tube, the neuroblasts of the nucleated mantle layer in the dorsal or alar plate of the spinal cord increase greatly in number and form the dorsal (or posterior) gray column (fig. 355A-E). The developing neuroblasts of the dorsal gray column become associated with the dorsal root fibers of the spinal nerves. Ventrally, the neuroblasts of the mantle layer increase in number in the basal plate area of the spinal cord and form a ventral (anterior) gray column. The ventral root fibers of the spinal nerves emerge from the ventral



gray column. In the region of the central canal the mantle layer forms the dorsal and ventral gray commissures which extend across the nerve cord joining the gray columns in the lateral walls of the cord. Somewhat later, a lateral gray column on either side may be formed between the dorsal and ventral gray columns.

As the above growth and development of the mantle layer is achieved, the marginal zone of the spinal cord also increases in size as nerve fibers from the developing neurons in the gray columns and in the spinal ganglia of the dorsal roots grow into the marginal layer between the neuroglia elements. Moreover, nerve fibers from developing neuroblasts in the brain grow posteriad in the marginal layer of the cord. As the growth and expansion of the dorsal and ventral gray columns toward the periphery of the spinal cord occurs, the marginal layer becomes divided into definite regions or columns known as funiculi. The dorsal funiculus, for example, lies between the dorsal median septum and the dorsal gray column while the ventral funiculus is bounded by the ventral median fissure and the ventral gray column. The lateral funiculus lies laterally between the dorsal and ventral gray columns (fig. 355F). Below the ventral gray commissure, fibers cross from one side of the cord to the other, forming the ventral white commissure.

Eventually the nerve fibers of each funiculus become segregated into fiber tracts. As a result, the dorsal funiculus becomes subdivided into the two fibertract bundles, the fasciculus gracilis near the dorsal medial septum and the fasciculus cuneatus near the dorsal gray column. Other fiber tracts are shown in figure 355F. (Consult Ranson, ’39, p. 110.)

b. Enlargements of the Spinal Cord

The spinal cord in many tetrapoda tends to show two enlarged areas, viz. (fig. 355G):

( 1 ) The brachial (cervical) enlargement in the area of origin of the brachial nerves;

(2) The lumbar (sacral) enlargement in the area of origin of the lumbosacral plexus.

Posteriorly the cord tapers toward a point, and anteriorly, in the region of the first spinal nerve, it swells to become continuous with the myelencephalon.

c. Enveloping Membranes of the Cord

Immediately surrounding the spinal cord is a delicate membrane, the pia mater, presumably developed from neural crest cells. More lateral is the arachnoid layer, developed probably from neural crest cells and mesenchyme. Between the pia mater and the arachnoid is the subarachnoid space containing blood vessels, connective tissue fibers, and a lymph-like fluid. Outside



of the arachnoid layer is a cavity, the subdural cavity. The external boundary of the subdural cavity is formed by the dura mater. The latter is a tough connective tissue membrane of mesenchymal origin (fig. 355H).

2. Development of the Brain

a. The Development of Specialized Areas and Outgrowths of the Brain

1) The Formation of the Five-part Brain. The primitive vertebrate brain from its earliest stages of development begins to show certain enlargements, sacculations and outpushings. Furthermore, it possesses two main areas which are non-nervous and membranous in character, namely, the thin roof plate of the rhombencephalon and the thin roof plate of the posterior portion (diencephalon) of the prosencephalon (figs. 354E; 356A). These thin roof plates ultimately form a part of the tela chorioidea. Vascular tufts, the chorioid plexi, also project from these roof plates into the third and fourth ventricles.

The anterior region of the primitive brain known as the prosencephalon or forebrain soon divides into the anterior t elenc ephalon and a more posterior diencephalon (fig. 354C-E). The telencephalon gives origin to two lateral outgrowths or pouches, the telencephalic vesicles (figs. 354E; 357E). The telencephalic vesicles represent the rudiments of the cerebral lobes. From the diencephalon, four or five evaginations occur, namely, a mid-dorsal evagination, the epiphysis or rudiment of the pineal body (fig. 356A) , and in front of the epiphysis a second mid-dorsal evagination occurs normally in most vertebrates, namely, the paraphysis (see Chapter 21); two ventro-lateral outgrowths, the optic vesicles (fig. 354B-D) from which later arise the optic nerves, retina, etc., and a mid-ventral evagination, the infundibulum. The infundibulum unites with Rathke’s pouch (figs. 354E; 356A), a structure which arises from the stomodaeum. Rathke’s pouch ultimately differentiates into the anterior lobe of the pituitary body (see Chapter 21 ).

The mesencephalon, unlike the fore- and hind-brain regions, does not divide. However, from the mesencephalic roof or tectum dorsal swellings occur which appear to be associated with visual and auditory reflexes. In fishes and amphibia, two swellings occur, the so-called optic lobes or corpora bigemina. In reptiles, birds and mammals four swellings arise in the tectum, the corpora quadrigemina. (fig. 357H-0).

The rhombencephalon divides into an anterior metencephalon and posterior medulla or myelencephalon (fig, 354E and G). Two cerebellar outpushings arise from the roof of the metencephalon.

The primitive five-part brain forms the basic embryonic condition for later brain development in all vertebrates.

2) The Cavities of the Primitive Five-part Brain and Spinal Cord. As, previously observed, the brain and spinal cord are hollow structures, and its generalized cavity is called the neural cavity or neurocoel (fig. 357A). From



the primitive neurocoel, special cavities in the brain arise, as follows (see figure 357A):

(1) The telencephalon is made up of the anterior part of the prosencephalon and two telencephalic vesicles. Each vesicle ultimately gives origin to a cerebral lobe. The cavities of the telencephalic vesicles are known as the first and second ventricles.

(2) The cavity of the posterior, median portion of the telencephalon and that of the diencephalon form the third ventricle.

(3) The roof of the original mesencephalon may give origin to hollow, shallow outpushings, but the cavity of the mesencephalon itself becomes a narrow passageway and is known as the cerebral aqueduct or the aqueduct of Sylvius.

(4) The cavity of the rhombencephalon is called the fourth ventricle.

b. The Formation of Cervical and Pontine Flexures

In addition to the primary or cephalic flexure previously described (p. 812) other flexures may appear in the developing vertebrate brain, especially in higher vertebrates. The cervical flexure develops at the anterior portion of the spinal cord, as it joins the myelencephalon. It involves the caudal portion of the myelencephalon, and the anterior part of the cord. It bends the entire brain region ventrally (see figure 357D and E). The latter flexure is absent in fishes, is present to a slight degree in the early neural tube of the amphibia, and is pronounced in reptiles, birds and mammals. The third or pontine flexure of the brain bends the brain dorsally. It arises in the mid-region of the rhombencephalon, in the area between the myelencephalon and the metencephalon. It appears later in development than the cephalic and cervical flexures, and is found only in higher vertebrates.

c. Later Development of the Five-part Brain

The various fundamental regions of the five-part brain develop differently in different vertebrates. Figure 357B-G and H-O illustrates the changes of the regions of the primitive five-part brain in the shark, frog, bird, dog, and human. For detailed discussion of the function of the various parts of the brain of the vertebrate, see Ranson, ’39.

D. Development of the Peripheral Nervous System

1. Structural Divisions of the Peripheral Nervous System

The peripheral nervous system integrates the peripheral areas of the body with the central nervous system. It is composed of two main parts,

( 1 ) the cerebrospinal system of nerves and

(2) the autonomic system. The latter is associated intimately with the cerebrospinal system.

telencephalon diencfphalon mesencephalon metencephalon


PREMUSCLE MASS OF sternomastoid

AND â–















Fio. 356. The cranial nerves; nuclei of origin and termination; functional components. {Note: The accompanying figures illustrate the nuclei of origin and nuclei of termination of the various cranial nerves. They are generalized figures and should be regarded only as approximate representations. This must be true, for the position of the respective nuclei within the brain “varies greatly in different orders of vertebrates” [Ranson]. This variation presumably is the result of a developmental principle known as neurohiotaxis. This principle postulates that the dendrites of a neuron together with the cell body move




toward the source from whence the neuron receives its stimulation. That is, the dendrites grow, and the neuron cell body as a whole moves, toward the particular nerve fiber tract from which the impulses are received. As these impulses and fiber tracts vary slightly with the particular environmental conditions under which the different animal groups live, the location of the nuclei within the brain correspondingly will vary to a degree within the respective vertebrate groups. It is- to be observed, also, that the nuclei of origin of the afferent fibers of the cranial nerves, and of the cerebrospinal nerves in general, are located outside of the central nerve tube, with the exception of the neuron cell bodies of the second or optic nerve which are located in the retina, an extension of the forebrain, and the mesencephalic nucleus of the fifth nerve. The nuclei of origin of the efferent fibers are placed within the latero-basal areas of the nerve tube (fig. 3551).)

(A) The nuclei of origin of the various motor components of the cranial nerves here are shown to be located within fairly definite regions along the antero-posterior axis of the vertebrate brain. Reference may be made to Fig. 3551, for the dorso-ventral distribution of these nuclei.

The following symbols are used:

1. Somatic motor fibers are shown in solid black.

2. Special visceral motor fibers are indicated in black with white circles.

3. General visceral motor fibers are black with white markings.

Nuclei of origin within the brain are as follows:

111 — black = Edinger-Westphal nucleus, origin of general visceral efferent fibers of Oculomotor Nerve

III — cross lines — nucleus of origin of somatic motor fibers of Oculomotor Nerve

IV — cross lines = nucleus of origin of somatic motor fibers of Trochlear Nerve

V — cross hatched = special visceral motor nucleus, origin of special visceral motor fibers of Mandibular division of Trigeminal Nerve

VI — cross lines = nucleus of origin of somatic motor fibers of Abducent Nerve

VII — cross hatched = special visceral motor nucleus of Facial Nerve

VII — black = superior salivatory nucleus (?), origin of general visceral motor fibers of Facial Nerve

IX — cross hatched = origin of special visceral motor fibers of Glossopharyngeal Nerve (this nucleus represents the anterior portion of nucleus ambiguus of Vagus Nerve)

IX — solid black = inferior salivatory nucleus (?), origin of general visceral motor fibers of Glossopharyngeal Nerve

X — cross hatched = nucleus ambiguus or origin of special visceral motor fibers of Vagus Nerve

X — solid black = dorsal motor nucleus, origin of general visceral motor fibers of Vagus Nerve

XI — cross hatched = probable nucleus of origin of special visceral motor fibers of Spinal Accessory Nerve

XII — cross lines = nucleus of origin of somatic motor fibers of Hypoglossal Nerve

(B) Sensory nuclei or nuclei of termination of fifth, seventh, ninth, and tenth cranial nerves, shown along the antero-posterior axis of the vertebrate brain. (The dorso-ventral distribution of these nuclei is presented in Fig. 3551.) The nuclei of termination of the eighth cranial nerve has been omitted. (Figs. A and B are schematized from data supplied by Ranson, 1939, The Anatomy of the Nervous System, Philadelphia, Saunders.)

(C) Cutaneous taste-bud branches of the right Facial Nerve in the fish, Ameiurus. (Redrawn from Johnston, 1906, The Nervous System of Vertebrata, Philadelphia, Blakiston, after Herrick.)

(D) Head of the pollack, Pollachius virens, revealing seventh and tenth cranial nerve distribution to lateral line system of the head. (Redrawn from Kingsley, 1912, Comparative Anatomy of Vertebrates, Philadelphia, Blakiston, after Cole.)



2. The Cerebrospinal System

The cerebrospinal system of nerves is composed of the cranial and spinal nerves. Two sets of neurons enter into the composition of the cranial and spinal nerves, viz.:

( 1 ) afferent neurons, whose fibers receive stimuli from certain receptor organs and convey the impulses to the central nervous system, and

(2) efferent neurons, with fibers which convey the impulses from the central nervous system to the peripheral areas. The central nervous system with its multitudes of association neurons thus acts to correlate the incoming impulses from afferent neurons and to shunt them into the correct outgoing pathways through the fibers of the efferent neurons (see figure 358A).

Most of the afferent or sensory neurons are located in ganglia outside of the central nerve tube, within the dorsal root ganglia of the spinal nerves and in the ganglia of the cranial nerves in close association with the brain (fig. 356B). On the other hand, the cell bodies of the somatic efferent or motor fibers are found within the gray matter of the central nerve tube, and the cell bodies of the visceral efferent or motor fibers are located within the gray matter of the central nerve tube and also in peripheral (autonomic) ganglia.

3. General Structure and Function of the Spinal Nerves

In each of the spinal nerves the nerve fibers are of four functional varieties, namely, visceral sensory (afferent); visceral motor (efferent); somatic sensory (afferent); and somatic motor (efferent). The visceral components are distributed to the glands, smooth muscles, etc., of the viscera located within the thoracic and abdominal cavities, together with the blood vessels of the general body areas. The somatic components innervate the body wall tissues including the skin and its appendages. A spinal nerve and its component fibers in the trunk region is shown in figure 358 A, and figure 358B shows this distribution in the region of the brachial plexus.

A typical spinal nerve is composed of the following general parts:

( 1 ) The dorsal or sensory root with its ganglion, and

(2) the ventral or motor root.

(3) Each spinal nerve divides into

(4) a dorsal ramus, and

(5) a ventral ramus. The ventral ramus may divide into

(6) a lateral branch and

(7) a ventral branch. Connecting with the spinal nerve also are

(8) the gray and white rami of the autonomic nervous system.

As the peripheral nerve fibers grow distad they become grouped together to form peripheral nerves. Each nerve in consequence is an association of



bundles or fasicles of fibers surrounded and held together by connective tissue. Most of the peripheral nerve fibers are myelinated. The connective tissue which surrounds a nerve is called the perineurium and that which penetrates inward between the fibers is the endoneurium (fig. 358C).

4. The Origin, Development and Functions of the Cranial Nerves

Consult diagrams, figures 356A and B, also 3551.

O. Terminal

The nervus terminalis is a little understood nerve closely associated with the olfactory nerve. It was discovered by F. Pinkus in 1894, in the dipnoan fish, Protopterus, after the other cranial nerves were described. In consequence it does not have a numerical designation. (Consult Larsell, ’18, for references and discussion.)

I. Olfactory

Arises from bipolar cells located in olfactory epithelium. These cells give origin to fibers which grow into the olfactory bulb to synapse with olfactorybulb neurons (fig. 356B).

Summary of functional components: Special visceral afferent fibers.

II. Optic

The optic nerve arises from neurons located in the retina of the eye. They grow niediad along the lumen of the optic stalk to form the optic nerve. In mammals part of the fibers from the median half of each retina decussate, i.e., cross over, and follow the fibers from the lateral half of the retina of the other eye into the brain (fig. 356B). In birds, however, decussation of the optic nerve fibers is complete, as it is in reptiles and fishes, and probably also in amphibians.

Summary of functional components: Special somatic afferent fibers, cell bodies in the retina. In fishes, there are efferent fibers in the optic nerve controlling, possibly, movements of retinal elements (Arey, ’16, and Arey and Smith, ’37).

III. Oculomotor

The third cranial nerve is composed mainly of somatic motor fibers which originate from neuroblasts in the anterior basal area of the mesencephalon. These fibers grow latero-ventrad from the mesencephalic wall to innervate the premuscle masses of the inferior oblique, inferior, medial and superior rectus muscles of the eyeball (fig. 356A).

Summary of functional components: ( 1 ) Somatic motor fibers controlling eye muscles indicated, (2) general somatic afferent (sensory) fibers, i.e. pro



prioceptive fibers for eye muscle tissue, (3) general visceral efferent fibers. The neuron bodies of the visceral efferent fibers are located in the EdingerWestphal nucleus of mesencephalon. The fibers from these neurons form the preganglionic fibers which terminate in the ciliary ganglion. The postganglionic fibers from cell bodies in ciliary ganglion innervate the intrinsic (smooth) muscles of the ciliary body and iris.

IV. Trochlear

The fourth cranial nerve arises from neuroblasts in the posterior ventral floor of the mesencephalon near the ventral commissure. The fibers grow dorsad and somewhat posteriad within the wall of the mesencephalon to the mid-dorsal line where they emerge to the outside and decussate (i.e. cross), the nerve from one side passing laterad toward the eye of the opposite side where it innervates the developing premuscle mass of the superior oblique muscle (fig. 356A).

Summary of functional components: ( 1 ) Somatic motor fibers controlling superior oblique muscle, (2) general somatic afferent (sensory) fibers, i.e. proprioceptive fibers from eye muscle tissue.

V. Trigeminal

The trigeminal nerve is a complex association of sensory and motor fibers (fig. 356A, B). It has the following divisions:

A. Ophthalmicus or Deep Profundus

Composed of somatic sensory fibers to the snout region. Fibers originate from neuroblasts in the dorso-anterior part of the neural crest cells which give origin to the Gasserian (semilunar) ganglion. This portion of the semilunar ganglion probably should be regarded as a separate and distinct ganglion. One fiber from each bipolar neuroblast grows anteriad toward the snout while the other fiber enters the wall of the metencephalon. These neurons later become unipolar.

Summary of functional components: General somatic afferent (sensory) fibers.

B. Maxillaris

The maxillary ramus of the fifth cranial nerve is composed of somatic sensory fibers from the upper jaw and snout and mucous membranes in these areas. The fibers arise from neuroblasts within the neural crest material which forms the central mass of the semilunar ganglion. One fiber from each bipolar neuroblast grows anteriad toward the snout while the other fiber grows mediad to enter the wall of the metencephalon along with fibers from the ophthalmic and mandibular divisions. These neurons later become unipolar.

Summary of functional components: General somatic afferent (sensory) fibers.



C. Mandibular is

The mandibular ramus is composed of general sensory (afferent) fibers with cell bodies lying in the mesencephalic nucleus of the fifth nerve (see figure 356A). Associated with these sensory fibers are motor fibers (generally spoken of as special visceral motor fibers) distributed to the muscles of mastication. The latter muscles arise from mesoderm associated with the first or mandibular visceral arch. During development the motor fibers arise from a localized mass of neuroblasts lying in the pons of the mctencephalon (see figure 356A), and they emerge from the ventro-lateral aspect of the pons and grow out toward the mandibular arch. Later they become associated with the sensory fibers observed above.

Summary of functional components: ( 1 ) General somatic afferent (sensory) fibers, of the proprioceptive variety, originating in mesencephalic nucleus of the fifth nerve (fig. 356A, B), (2) special visceral efferent (motor) fibers to muscles of mastication from motor nucleus noted above.

VI, Abducens

The word abducens means to lead away, or draw aside. It is applied to the sixth cranial nerve because it innervates the lateral rectus muscle of the eyeball whose function is to pull the eye away or outward from the median line. It is composed almost entirely of somatic efferent (motor) fibers whose origin is within a nucleus lying in the caudo-ventral area of the pons (fig. 356A). In the embryo, ncuroblasts in this area grow outward from the ventro-lateral wall of the pons and forward into the developing premuscle mass of the external (lateral) rectus muscle.

Summary of functional components: (1) Somatic efferent fibers, (2) general somatic afferent fibers, i.e. proprioceptive fibers from the external rectus muscle.

VII. Facial

In higher vertebrates this nerve is composed largely of motor fibers of the special visceral variety innervating the musculature derived from the hyoid visceral arch. As indicated previously (Chap. 16) the muscle tissue of this arch forms the facial (mimetic) and platysma musculature of mammals and the posterior belly of digastric and stylohyoid muscles. In fishes muscle tissue is restricted to the region of the hyoid arch and is concerned with movements of this arch. The motor fibers distributed to the hyoid arch of fishes are located in the hyomandibular branch of the facial nerve (see figure 3571). Aside from these special visceral motor fibers, sensory fibers are present whose cell bodies lie within the geniculate ganglion of the facial nerve. The sensory fibers which innervate some of the taste buds on the anterior two-thirds of the tongue in mammals are special visceral afferent fibers coursing in the chorda tympani nerve, whereas those along the pathway of the facial nerve are



general visceral sensory fibers providing deep sensibility to the general area of distribution of the facial nerve. The special visceral afferent fibers to the taste bud system are prominent elements in the seventh cranial nerve of many fishes (fig. 356C). In fishes also, the seventh cranial nerve contains lateralline components distributed to the lateral-line organs of the head (fig. 356D).

The special motor fibers of the facial nerve arise from neuroblasts located in the pons as indicated in figure 356A, and the general visceral motor fibers take origin from cell bodies in the nucleus salvatorius superior.

Summary of components: (1) Special visceral efferent (motor) fibers to musculature arising in area of hyoid arch, (2) in mammals, preganglionic general visceral efferent fibers by way of chorda tympani nerve to submaxillary ganglion; and from thence, postganglionic fibers to submaxillary and sublingual salivary glands. (3) Special visceral afferent fibers to taste buds on anterior portion of tongue by way of chorda tympani nerve; in fishes, special visceral afferent fibers are extensive. (4) General visceral afferent fibers. (5) In fishes, lateral-line components to head region are present.

VIII. Acoustic

The acoustic nerve contains special somatic sensory components which receive sensations from the special sense organs derived from the otic vesicle. The otic vesicle differentiates into two major structures, viz.: (1) one related to balance or equilibration, and (2) the other concerned with hearing or the detection of wave motions aroused in the external medium. This differentiation is obscure in fishes. However, in those vertebrates which dwell in water other hearing devices may be used aside from those which may involve the developing ear vesicle. One aspect of the mechanism which enables waterdwelling vertebrates to detect pressure or wave motions of low frequency in the surrounding watery medium is the lateral line system associated with the fifth, seventh, ninth and tenth cranial nerves.

In accordance with the differentiation of the otic vesicle into two senseperceiving organs, the sensory neurons of the acoustic ganglion of the eighth cranial nerve become segregated into two ganglia, namely, ( 1 ) the vestibular ganglion containing bipolar neurons which transmit proprioceptive stimuli through the vestibular nerve from the organ of equilibration composed of the utricle, saccule and semicircular canals, and (2) the spiral ganglion containing bipolar neurons which transmit somatic sensations from the spiral or hearing organ (fig. 361H).

Summary of functional components: (1) Special somatic afferent fibers of proprioceptive variety associated with equilibration, (2) special somatic afferent fibers of exteroceptive variety, associated with hearing.

IX. Glossopharyngeal

The glossopharyngeal nerve is associated with the third visceral arch and nearby areas of the pharynx. It has two major components; one of these



components is motor, innervating the musculature derived from the embryonic third visceral arch, while the other component is sensory. The sensory components are derived from neuron bodies within the superior and petrosal ganglia (fig. 356B). Aside from receiving general sense impulses from the pharyngeal area, many of these sensory components are associated with the taste buds on the caudal portion of the tongue. The latter components thus are special sensory components.

The visceral motor (efferent) components to the musculature derived from the third visceral arch arise from neuroblasts located in the ventro-lateral floor of the anterior part of the myelencephalon (fig. 356A). The sensory components take origin from neural crest cells located in the region of the third visceral arch. Fibers from these neuroblasts grow mediad into the nerve tube, and latero-ventrad toward the third visceral arch region.

Summary of functional components: ( 1 ) General visceral afferent fibers with cell bodies in petrosal ganglion whose peripheral fibers terminate in the posterior tongue region and in the pharyngeal area, (2) special visceral afferent fibers with cell bodies in petrosal ganglion whose peripheral fibers contact the taste buds in the posterior third of the tongue, (3) special visceral efferent fibers to musculature derived from the third visceral arch. In mammals, this musculature is the stylopharyngeus muscle, (4) in mammals: general visceral efferent fibers, composed of preganglionic fibers from neurons in inferior salivatory nucleus located probably in the region between the pons and medulla pass to the otic ganglion. Postganglionic fibers from otic ganglion innervate the parotid gland. (5) In fishes: lateral-line components are present and distributed to posterior head region. In mammals, some general somatic afferent fibers from cell bodies in the superior ganglion appear to innervate cutaneous areas in the ear region.

X. Vagus

The tenth cranial or vagus nerve is composed of several functional components. It is a prominent nerve associated with the autonomic nervous system as indicated below. In addition to these autonomic components, the functional components of the tenth cranial nerve are related to the visceral arches caudal to the third visceral arch. The tenth cranial nerve thus supplies several visceral arches. In consequence, it must be regarded as a composite nerve, arising from extensive motor nuclei, the dorsal motor nucleus and the nucleus ambiguus in the ventro-lateral area of the myelencephalon (fig. 356A). The tenth nerve has two main ganglia, the jugular and nodose ganglia. The motor fibers arise from neuroblasts in the nuclei mentioned above and grow out laterally to the visceral arch area, and the sensory components take origin from neuroblasts of neural crest origin which become aggregated in the jugular and nodose ganglia.

Summary of functional components: (1) Special visceral afferent fibers


Fig. 357. External morphological development of various vertebrate brains. (A) Diagram showing the fundamental regional cavities of the primitive five-part vertebrate brain. (B-G) External morphological changes of the developing human brain and cranial nerves. (Redrawti, somewhat modified, from Patten, 1946, Human Embryology, Philadelphia, Blakiston, adapted primarily from Streeter and reconstructions in Carnegie Collection.) (B) 20 somite embryo, probably 3V2 weeks. (C) 4 mm. embryo, about 4 weeks. (D) 8 mm. embryo, about 51/3 weeks. (E) 17 mm. embryo, about 7 weeks. (F) 50-60 mm. embryo, about 11 weeks. The brain now begins to assume the configuration shown by the chick at hatching (see Fig. 347L and M). Roman numerals III, IV, V, VI, VII, IX, X, XI and XII indicate cranial nerves. See Fig. 356A and B for functional components of the cranial nerves at this time. (G) Lateral view of brain at about the ninth month. (H, I, and I') Adult form of the brain of Squalus acanthias. It is to be observed that the brain of Squalus acanthias loses the marked cephalic flexure (see Fig. 347A) present in the early embryo, and assumes a straightened form during the later stages of its development. (H and I ventral and dorsal views, respectively, drawn from dissected specimens; T redrawn and slightly modified from Norris and Hughes, 1919, J. Comp. Neurol., 31.) (J and K) Ventral and dorsal




whose cell bodies lie in nodose ganglion with peripheral terminations in taste buds of pharyngeal area, (2) general visceral afferent fibers whose cell bodies lie in nodose ganglion, with peripheral distribution to pharynx, esophagus, trachea, thoracic and abdominal viscera, (3) general somatic afferent fibers with cell bodies in jugular ganglion and peripheral distribution to external ear region, (4) special visceral efferent fibers to striated musculature of pharyngeal area; cell bodies lie in nucleus ambiguus, (5) general visceral efferent fibers. Preganglionic cell bodies in dorsal motor nucleus; terminate in sympathetic ganglia associated with thoracic and abdominal viscera, (6) in fishes: a prominent lateral line component is present which is distributed along the lateral body wall.

The special visceral motor fibers of the vagus are associated with musculature arising from the caudal visceral arches.

XI. Spinal Accessory

The spinal accessory nerve arises in close association with the vagus. It is composed mainly of motor fibers and distributed to musculature derived from premuscle masses in the caudal branchial area (fig. 356A). They may be regarded as special visceral motor fibers.

Summary of functional components: ( 1 ) Special visceral efferent fibers whose cell bodies lie in nucleus ambiguus and in anterior part of spinal cord and distributed to trapezius, and sternocleidomastoid, muscles and striated muscles of pharynx and larynx, (2) general visceral efferent fibers associated with vagus nerve, with cell bodies in dorsal motor nucleus of vagus.

XII. Hypoglossal Nerve

The twelfth cranial nerve is a somatic motor nerve composed mainly of efferent fibers distributed to the hypobranchial or tongue region. These fibers arise from neuroblasts in an extensive nuclear region from the anterior cervical area along the floor of the myelencephalon near the midventral line (fig. 356A). In lower vertebrates these fibers innervate certain of the anterior trunk myotomes whose muscle fibers travel ventrad into the hypobranchial area. In higher vertebrates the hypoglossal nerve fibers innervate the tongue and associated muscles.

Fig. 357 — Continued

views, respectively, of the adult form of the brain in the frog, Rana cateshiana. Like the developing brain in Squalus, the brain of the developing frog loses its pronounced cephalic flexure as development proceeds. (L and M) Ventral and dorsal views, respectively, of the adult form of brain in the chick shortly before hatching. The cervical, pontine, and cephalic flexures are partly retained in developing brain of chick, and in this respect it resembles the developing mammalian brain. Compare these diagrams with Figs. 354E, 259. (N and O) Ventral and dorsal views, respectively, of the adult brain of the dog. (Redrawn from models.)







posttrematic Rami of the


Fig. 357 — Continued

For legend see p. 832.

Summary of functional components: (1) Somatic motor fibers; (2) somatic sensory, i.e., proprioceptive fibers, from tongue musculature,

5. The Origin and Development of the Autonomic System a. Definition of the Autonomic Nervous System The autonomic nervous system is that part of the peripheral nervous system which supplies the various glands of the body together with the musculature









Fig. 357 — Continued For legend see p. 832.

of the heart, blood vessels, digestive, urinary and reproductive organs, and other involuntary musculature. It differs from the cerebrospinal nerve series in its efferent system of neurons, and not in the afferent system. The latter is composed of ordinary afferent neurons located in the ganglia of the cerebro



Spinal series and these differ from the somatic sensory neurons of the dorsal root ganglia only in that they convey sensations from the viscera instead of the body wall and cutaneous surfaces* On the other hand, the efferent system of neurons is unlike that of the cerebrospinal series in that two neurons are involved in conveying the efferent nerve impulse instead of one as in the cerebrospinal series. The body of one of these two neurons, the preganglionic neuron, lies within the brain or spinal cord, whereas the cell body of the other, the postganglionic neuron, is associated with similar cell bodies within certain aggregations called sympathetic ganglia (fig. 358A). The axons of the postganglionic neurons run to and end in the cardiac and blood vessel musculature, gland tissue and smooth musculature in general throughout the body. According to Ranson, T8, p. 308, “The autonomic nervous system is that functional division of the nervous system which supplies the glands, the heart, and all smooth muscle, with their efferent innervation and includes all general visceral efferent neurones both pre- and postganglionic.”

b. Divisions of the Autonomic Nervous System

There are two main divisions of the autonomic system, viz.:

(1) The thoracicolumbar autonomic system, also called the sympathetic division of the autonomic system, and

(2) The craniosacral autonomic system, also called the parasympathetic division of the autonomic system (see figure 358D).

The thoracicolumbar outflow of efferent fibers has preganglionic fibers which pass from the spinal cord along with the thoracic and upper (anterior) lumbar spinal nerves, whereas the preganglionic fibers of the craniosacral outflow depart from the central nervous system via cranial nerves III, VII, IX, X and XI, and in the II, III and IV sacral nerves.

c. Dual Innervation by Thoracicolumbar and Craniosacral Autonomic


Most structures innervated by the autonomic nervous system receive a double innervation, one from the sympathetic and the other from the parasympathetic division, both, in many instances, having opposite functional effects upon the organ tissue.

Examples of this dual innervation are:

1) Autonomic Efferent Innervation of the Eye. Preganglionic cell bodies in

oculomotor nucleus, fibers passing with nerve III to ciliary ganglion. Postganglionic cell bodies in ciliary ganglion; postganglionic fibers by way of short ciliary nerves to ciliary muscle and circular muscle fibers of iris. Function: Accommodation of eye and decrease in diameter of pupil. The foregoing innervation is a part of the cranio-sacral autonomic outflow. A parallel inner



vation to the iris of the eye occurs through the thoracicolumbar autonomic system as follows:

Cell bodies of preganglionic neurons in intermedio-lateral column of spinal cord, from which preganglionic fibers pass to superior cervical ganglion of autonomic nervous system. Cell bodies of postganglionic fibers lie in the superior cervical ganglion and fibers pass from this ganglion along the internal carotid plexus to the ophthalmic division of the fifth nerve, and from thence along the long ciliary and nasociliary nerves to iris. Function: dilation of the pupil.

2) Autonomic Efferent Innervation of the Heart. Preganglionic cell bodies

in dorsal motor nucleus of vagus in myelencephalon. Fibers pass by way of vagus nerve to terminal (intrinsic) ganglia of the heart. Postganglionic cell bodies in terminal ganglia of heart; postganglionic fibers pass to heart muscle. Function: slows the heart beat. The foregoing represents the craniosacral autonomic or parasympathetic innervation. The corresponding sympathetic innervation is as follows:

Preganglionic cell bodies in intermedio-lateral column of spinal cord; preganglionic fibers pass to superior, middle and inferior cervical ganglia of sympathetic ganglion series. Postganglionic cell bodies in cervical ganglia from which postganglionic fibers pass via cardiac nerves to cardiac musculature.

Function: acceleration of heart beat.

d. Ganglia of the Autonomic System and Their Origin

The ganglia of the autonomic nervous system represent aggregations of the cell bodies of postganglionic neurons; the cell bodies of the preganglionic neurons lie always within the central nervous system. These autonomic ganglia arise from two sources; viz.:

1 ) The neural crest material of the dorsal root ganglion of the spinal nerves and the neural crest material associated with certain cranial nerves, and

2) from cells of the neural tube which migrate from the tube along the forming ventral or efferent nerve roots of the spinal nerves (Kuntz and Batson, ’20).

These migrating neural cells become aggregated to form three sets of ganglia as follows:

1) The sympathetic chain ganglia lying on either side of the vertebral column.

2) The collateral or subvertebral ganglia located between the chain ganglia and the viscera. Examples of collateral ganglia are the coeliac, superior mesenteric and inferior mesenteric ganglia.

3 ) The terminal or intrinsic ganglia lie near or within the organ tissue such

as the ciliary and submaxillary ganglia.



Fig. 358. General structural features of spinal nerves, and of nerve fibers terminating in muscle tissue. (A) Diagrammatic representation of a spinal nerve in the region of the* mammalian diaphragm showing functional components. Three facts are evident relative to the components of a typical spinal nerve, viz., (1) The somatic efferent motor neuron lies within the central nerve tube; its fiber extends peripherad to the effector organ. One neuron therefore is involved in the somatic efferent system (see Fig. 352A). (2) Unlike the somatic efferent system, the visceral efferent (motor) system is composed of a chain of two neurons, a preganglionic neuron whose cell body lies within the central nerve tube, and a postganglionic neuron whose cell body lies in one of the peripheral ganglia. (3) The somatic afferent (sensory) and visceral afferent (sensory) fibers both possess but one neuron whose cell body lies within the dorsal root ganglion. The somatic afferent fiber connects with a sense or receptor organ lying somewhere between the viscera and the external surface (i.e., cutaneous surface) of the body, whereas the visceral afferent fiber contacts the structural makeup of the visceral structures. (B) A spinal nerve in the region of the brachial plexus. The main difference between this type of nerve and the typical spinal nerve resides in the fact that the ventral ramus proceeds into the limb and not into the body wall. Before proceeding into the limb it inosculates with the ventral rami of other nerves to form the brachial plexus. (C) Portion of a transverse section of the sciatic nerve of a newborn showing groups of nerve fibers joined together into bundles. Each nerve-fiber bundle is surrounded by connective tissue, the perineurium, and is partly divided by septa of connective tissue, the endoneuriiim. External to the perineurium is the epineurium, or the connective tissue which holds the entire nerve together (Redrawn from Maximow and Bloom, 1942, A Textbook of Histology, W. B. Saunders Co., Philadelphia, after Schaffer.) (D) Diagram of the autonomic efferent system of neurons and ganglia. The parasympathetic (craniosacral) outflow is shown in heavy black lines with white spaces; the sympathetic (thoracicolumbar) outflow is represented by ordinary black lines. (Adapted from Ranson, 1939, The Anatomy of the Nervous System, Philadelphia, Saunders, after Meyer and Gottlieb.)

G. cerv. sup. = superior cervical ganglion G. stellatum = inferior cervical or stellate ganglion G. mes. sup. = superior mesenteric ganglion G. mes. inf. = inferior mesenteric ganglion G. pelv. = pelvic ganglion

Neurohumoral substances are produced at the terminal (effector) tips of the various autonomic nerve fibers. A substance similar to adrenalin appears to be produced at the tips of the sympathetic nerves proper, whereas in the case of the parasympathetic fibers the substance is acetylcholine. These humoral substances stimulate the effector structures. (E, F, and G) Nerve endings associated with muscle tissue. (E) Effector (motor) nerve endings associated with cardiac or smooth muscle. Sympathetic motor endings terminate in small swellings. This figure portrays sympathetic motor endings on a smooth muscle cell of an artery of the rabbit’s eye. (Redrawn from Maximow and Bloom, 1942, A Textbook of Histology, Philadelphia, Saunders, after Retzius.) (F) Another example of the termination of sympathetic nerve fiber endings on smooth muscle fibers. In this instance the bronchial musculature is the effector organ. (Redrawn from Maximow and Bloom, 1942, A Textbook of Histology, Philadelphia, Saunders, after Larsell & Dow.) (G and G') Nerve endings in striated muscle. (G redrawn from Ranson, 1939, The Anatomy of the Nervous System, Philadelphia, Saunders, after Huber & De Witt; G' redrawn from Maximow and Bloom, 1942, A Textbook of Histology, Philadelphia, Saunders, after Boeke.) (G) Represents a neuromuscular end organ of a sensory nerve fiber terminating within a muscle spindle in striated muscle from a dog. These muscle spindles are in the form of a connective tissue capsule which invests spindle-shaped bundles of muscle fibers. Within this capsule, large myelinated nerve fibers terminate in non-myelinated branches which spiral around the muscle fibers or end in flattened discs. (G') Represents a somatic motor (efferent) nerve fiber terminating in a motor plate within a striated muscle fiber. The motor plate is composed of an irregular mass of sarcoplasm below the sarcolemma of the muscle fiber. This motor plate receives the naked terminal ramifications of the nerve fiber.

Fig. 358. (See facing page for legend,) 839

Fig. 359. Types of peripheral sense receptors (see also Fig. 358G). (A) Meissner's

tactile corpuscle. Consists of a thin connective tissue capsule. One or more myelinated nerve fibers enter the . capsule, where the myelin sheaths are lost. These terminating non-myelinated fibers break up into branches which form a complex mass of twisting coils. The coils show varicose enlargements. Found in the dermis of feet, hands, lips, forearms. (B) End-hulb of Krause. Small rounded bodies somewhat resembling Meissner’s corpuscles. Found in lips, conjunctiva, and edge of cornea. (C) Pacinian corpuscle. This type of nerve ending is in the form of a large, oval corpuscle composed of concentric layers of connective tissue. The central axis of the corpuscle receives the




The general arrangement of these ganglia and the autonomic nerve fibers to the spinal nerve series is shown in figure 358A. It is to be observed that only two neurons, a preganglionic and a postganglionic, are involved in the efferent chain regardless of the number of ganglia traversed.

E. The Sense or Receptor Organs

1. Definition

The sense organs are the sentinels of the nervous system. Endowed particularly with that property of living matter known as irritability, they are able to detect changes in the environment and to transmit the stimulus thus aroused to afferent nerve fibers. However, the perceptive ability of all sense organs is not the same, for specific types of sense receptors are developed specialized in the detection of particular environmental changes.

There are two general areas of sensory reception, viz.; (1) The somatic sensory area, and (2) the visceral sensory area. The location of somatic and visceral areas in the myelencephalon are shown in figure 3551.

The somatic sensory organs are associated with the general cutaneous surface of the body and also in tissues within the body wall. Consequently, this area may be divided for convenience into two general fields, namely, (1)

Fig. 359 — Continued

terminal ends of one or more unmyelinated fibers, and also, in addition, the terminal end of a myelinated fiber which loses its myelin as it enters the axial core of the corpuscle. Side branches arise from the central core of nerve fibers. Found in deeper parts of dermis, and also in association with tendons, joints, intermuscular areas as well as in the mesenteries of the peritoneal cavity, and the linings of the pleural and pericardial cavities. (D) Nerve endings in skin and hair follicles. As the myelinated fibers enter the skin they break up into smaller myelinated fibers. After many divisions the myelin sheaths are lost, and finally the neurilemma also disappears. The free nerve endings enter the epidermis and after other divisions form a network of terminal fibers among the epidermal cells. Below the stratum germinativum of the skin, some of the fibers terminate in small, leaf-like enlargements around the hair-follicles below the level of the sebaceous glands. (A-D, redrawn and somewhat modified from Ranson, 1939, The Anatomy of the Nervous System, Philadelphia, Saunders.) (E) Part of longitudinal section of the lateral line canal of a Mustelus “pup” at the level of the first dorsal fin. Observe termination of nerve fibers among groups of sensory hair cells. The lateral line canal communicates with the surface at intervals by means of small tubules. (Redrawn and modified from Johnson, 1917, J. Comp. Neurol., 28.) (F) Transverse section of

lateral line canal, higher magnification, showing termination of nerve endings among the secondary sense (hair) cells. (Redrawn from Johnson, 1917, J. Comp. Neurol., 28.) (G) The lateral line sensory cord is shown growing posteriad within the epidermal pocket of a 21 mm. embryo of Squaliis. (Redrawn from Johnson, 1917, J. Comp. Neurol., 28.) (H) Taste bud of human. (Redrawn from Neal and Rand, 1939, Chordate Anat omy, Philadelphia, Blakiston.) (I) Sagittal section through human nasal cavity depicting nasal conchae (turbinates) and various openings leading off from the lateral wall of the nasal cavity. The olfactory area of the mucous membrane extends over the superior concha and medially over the upper part of the nasal septum. Observe opening of eustachian tube (tuba auditiva).



The exteroceptive or general cutaneous field, having sense organs detecting stimuli at or near the surface of the body, and (2) the proprioceptive field, with sense organs located in the body-wall tissues, such as striated muscles, tendons, joints and the equilibration structures of the internal ear.

The visceral sensory organs receive stimuli from the interoceptive field, that is, the visceral structures of the body.

2. Somatic Sense Organs a. Special Somatic Sense Organs

The visual organs, the ear, and in water-living vertebrates the lateral-line system, are sense organs of the special variety.

/?, General Somatic Sense Organs

These structures are in the form of free nerve endings, terminating among cells and around the roots of hairs, or they are present as encapsulated nerve endings such as the corpuscles of Meissner, end bulbs of Krause, and Pacinian corpuscles (fig. 359A-D).

3. Visceral Sense Organs a. Special Visceral Sense Organs

The taste buds of various sorts, located generally on the tongue, mucous surface of the buccal cavity and pharynx and in some fishes on the external body surface are specialized visceral sense organs (fig. 285E).

In most craniates the paired olfactory organs are exteroceptive in function, although, possibly, olfactory organs may be regarded as primitively interoceptive. The olfactory organ is regarded generally as a special visceral sense organ.

b. General Visceral Sense Organs

General visceral sense organs are located among the viscera of the body. They represent free-nerve endings lying in the walls of the digestive tract and other viscera. They respond to mechanical stimuli.

4. The Lateral-line System

The lateral-line organs are a specialized series of organs located in the cutaneous areas of the body. They are found in fishes and water-living amphibia. A sense organ of the lateral-line system is composed of a patch of hair cells or neuromasts, columnar in shape, possessing cilia-like extensions at the free end (fig. 359E). Basally the hair cells are associated with the terminal fibrillae of sensory nerves. The hair cells are supported by elongated, sustentacular elements. In cyclostomous fishes the neuromasts are exposed to the surface, but in Gnathostomes they lie embedded within a canal system


Tlie Development of tlie Coelomic Cavities

A. Introduction

1. Definitions

2. Origin of the primitive splanchnocoelic coelom

B. Early divisions of the primitive splanchnocoelic coelom

1. Formation of primitive suspensory structures

2. Formation of the primitive transverse division of the body and the primary pericardial and peritoneal divisions of the coelom

a. Lateral mesocardia

b. Formation of the liver-septum transversum complex

1) Foritiation of the liver-septum complex through modification of the ventral mesentery by liver outgrowth

2) Formation of the liver-septum complex in the human embryo

c. Formation of the primary septum transversum

C. Coelomic changes in fishes, amphibians, reptiles, and birds

1. In fishes

2. In amphibians, reptiles, and birds

D. Formation of the coelomic cavities in mammals

1. Formation of the pleuropericardial membrane

2. Development of the pleuroperitoneal membrane

E. Development of independent pericardial walls

1. The arrangement of the parietal pericardial wall in fishes

2. Formation of an independent parietal pericardial wall in the chick

3. Formation of the independent parietal pericardial wall in amphibians and reptiles

4. Separation of the parietal pericardial wall in mammals

F. The mammalian diaphragm

G. The pulmonary diaphragm or aponeurosis of the chick

H. The omental bursa

I. The formation of various ligaments in the stomach-liver region

1. The gastro-hepatic and hepato-duodenal ligaments

2. The coronary ligament of the liver

3. The falciform ligament of the liver

4. The gastro-splenic ligament

A. Introduction

1. Definitions

The coelomic cavities are the spaces which come to surround the various viscera of the body such as the pericardial cavity around the heart, the pleural




cavities surrounding the lungs, and the peritoneal cavity in which lie the stomach, intestines, reproductive organs, etc. These coelomic spaces and recesses arise from a generalized basic condition known as the primitive splanchnocoelic coelom. The primitive splanchnocoelic coelom is the elongated cavity which extends throughout the trunk region beginning just anterior to the heart and continuing posteriorly to the base of the tail. It encloses the developing heart and the developing mesenteron (gut) from the esophageal region posteriorly to the anal region.

2. Origin of the Primitive Splanchnocoelic Coelom

As observed previously (Chapter 10) the elongated mesodermal masses lying along either side of the developing neural tube, notochord, and enteric tube have a tendency to hollow out to form a cavity within. That is, like the neural, gut, and epidermal areas of the late gastrula, the two mesodermal masses tend to assume the form of tubes.

In the case of Amphioxus, each individual somite forms a cavity, the myocoel. These myocoels merge on either side in their ventral halves to form an elongated splanchnocoel below the horizontal septum (see page 506). Later the two splanchnocoels fuse below the developing gut to form the single splanchnocoelic coelom which comes to surround the gut. In the vertebrate group, however, the two elongated splanchnocoels on either side of the developing gut tube and heart form directly in the hypomeric (lateral plate) area of the mesodermal masses without a process of secondary fusion as in Amphioxus. In the upper part of each mesodermal mass, that is in the epimere, and to some extent also in the mesomere (nephrotomic plate) in the vertebrate group as in A mphioxus, there is a tendency for the coelomic spaces to appear in segmental fashion within the primitive somites and within the anterior portion of the mesomere. These individual spaces within the somites are called myocoels, and the spaces which arise in the segmented portion of the nephrotome are called the nephrocoels.

In young shark embryos, such as the 3-4 mm. embryo of Squalus acanthias, and in amphibian embryos of the early post-gastrular period, the myocoelic and nephrocoelic portions of the coelom are continuous dorso-ventrally with the splanchnocoelic coelom (fig. 217G and H). (Actually, during the early stages of coelomic development within the mesodermal masses, in the shark and amphibian embryos, the coelom within the epimere and nephrotomic portions of the mesoderm is continuous antero-posteriorly and it is only after the appearance of the primitive somites and segmentation within the nephrotome that they become discontinuous.) On the other hand, in the embryos of higher vertebrates, the respective myocoels within the somites appear later in development, and in consequence they are always separated from the splanchnocoel. Similarly, the nephrocoelic coelom also arises later and only the separate nephrocoels which develop within the pronephric tubules



and certain types of mesonephric tubules make contact with the splanchnocoelic portion of the coelom.

In all vertebrates (see figures 254, 332F-M) the formation of the primitive, generalized coeiomic cavity proper or generalized splanchnocoelic portion of the coelom is formed by the fusion around the developing heart and gut structures of the two elongated splanchnocoels present in the hypomeric portions of the mesodermal masses as described below.

B. Early Divisions of the Primitive Splanchnocoelic Coelom

1. Formation of Primitive Suspensory Structures

The splanchnic walls of the early coeiomic cavities (splanchnocoels) within the two hypomeres become apposed around the structures, lying in the median plane (fig. 254). In the region of the heart, this apposition gives rise to the dorsal and ventral mesocardia and to the epimyocardium of the heart itself (fig. 254A, B) and, in the region of the stomach and intestine, it produces the dorsal and ventral mesenteries of the gut tube and various ligaments, connecting one organ with another. The mesenchyme which arises from the two splanchnic layers also gives origin to the muscles and connective tissues of the gut and its evaginated structures (fig. 31 lA, B). The ventral mesocardium disappears in all vertebrates (Chap. 17). The dorsal mesocardium may persist for a while but eventually disappears entirely or almost entirely (Chap. 17). The dorsal mesentery is present constantly in reptiles and mammals but may be perforated and reduced in the intestinal area in other vertebrate classes, so that little of the dorsal mesentery remains to suspend the intestine in certain cases as, for example, in the shark. The dorsal mesentery above the stomach, the mesogastrium, and also the ventral mesentery in the immediate region between the stomach and liver and between the liver and the ventral body wall persist in all vertebrates. As a rule, however, the ventral mesentery disappears caudal to the liver with the exception of dipnoan and anguilliform fishes and the ganoid fish, Lepisosteus. In these forms the ventral mesentery tends to persist throughout the peritoneal cavity. It follows, therefore, that the two bilaterally developed, splanchnocoelic cavities tend to merge into one cavity or generalized splanchnocoel with a partial retention in certain areas of the splanchnic layers of the two hypomeres which act as suspensory ligamentous structures for the viscera.

2. Formation of the Primitive Transverse Division of the Body and the Primary Pericardial and Peritoneal Divisions of the Coelom

The primitive splanchnocoelic coelom soon becomes divided into the pericardial coelom, surrounding the heart, and the peritoneal or abdominal coelom, surrounding the digestive viscera, by the formation of the lateral mesocardia











dorsal pancreas





Fig. 362. The lateral mesocardia form the initial division of the embryonic coelom (A-1 and A-2) represent idealized sections through the vertebrate embryonic body in £ plane bet\veen the caudal limits of the sinus venosus and the anterior extremity of th( potential liver region of the embryo. (A-1) Diagram of the initial stage of separatior of the pericardial and peritoneal coelomic cavities in many vertebrates. Two dorsal anc two ventral recesses or passageways above and below the lateral mesocardia and latera horns of the sinus venosus are evident. These passageways communicate with the peri cardial and peritoneal divisions of the primitive coelom. (A-2) Separation of primitive




and the primitive septum transversum which develop in relation to the converging veins of the sinus venosus and the ventro-cephalic growth of the liver rudiment. In other words, a ventral partition is established across the primitive splanchnocoelic coelom in a plane which separates the caudal end of the heart (i.e., sinus venosus) from the anterior limits of the liver. This primitive transverse partition partially separates the primitive splanchnocoelic coelom into two main divisions:

( 1 ) a cephalic compartment, the pericardial cavity, around the heart and

Fig. 362 — Continued

coelom into anterior pericardial and posterior peritoneal areas in early human embryo. The precocious development of the caudal wall of the parietal pericardium obliterates the ventral recesses shown in A-1 previous to septum transversum formation and the outgrowth of the liver rudiment. Communication between pericardial and peritoneal coelomic divisions is possible only through the dorsal parietal recesses (dorsal pericardioperitoneal canals). (B) Schematic diagram representing the initial division by the lateral mesocardia of the primitive coelomic cavity into anterior pericardial and posterior peritoneal divisions in an embryo of Squalus acanthias 10 mm. long. The liver outgrowth has been extended forward slightly for diagrammatic purposes. (C) Initial division, by the lateral mesocardia, of the primitive coelom in the 72 hr. chick embryo. Due to the depressed condition of the anterior end of the body much of the heart appears in the section below the sinus venosus and lateral mesocardia. However, if the embryo were straightened and the atrium, etc., of the heart pushed forward, the structural conditions would appear much the same as in B. The dorsal parietal recesses appear on either side of the esophagus. (D) Semidiagrammatic section through caudal end of sinus venosus of 22 mm. shark embryo. The dorsal closing folds are developing on either side of the esophagus, thus closing the dorsal recesses. The liver rudiment is expanding within the substance of the ventral mesentery caudal to the heart to form the liver’Septiirn transversum complex. The latter structure obliterates the ventral recesses below the lateral mesocardia. (E) Diagrammatic representation of the forward and ventral growth of the developing liver within the substance of the ventral mesentery to form the liverseptum transversum complex. (See fig. 363D.) Observe: ventral parietal recesses are obliterated by the forward growth of this complex of tissues. The arrow denotes the passageway from the pericardial coelom into the peritoneal coelom through the dorsal parietal recesses (dorsal pericardioperitoneal canals). (F) Early stage in development of human heart and septum transversum showing ingrowth of somatopleural mesoderm between the previously formed caudal wall of the parietal pericardial membrane (see A-2) and the entoderm of the anterior intestinal portal. (Redrawn from Davis, 1927, Carnegie Inst. Public. 380, Cont. to Embryology, 107.) (G) Later stage of human

heart development. Mesodermal partition (septum transversum) is present as a thickened mass of tissue below the developing sinus venosus and between the caudal wall of the parietal pericardium and the gut entoderm. (Redrawn from Davis, see fig. 362F, for reference.) (H) Lateral dissection of fifth week human embryo to show ingrowth of liver tissue into thickened septum transversum. (Redrawn from Patten, 1946, Human Embryology, Blakiston, Philadelphia.) Arrow denotes passageway (dorsal parietal recess; pericardioperitoneal canal; pleural canal) between pericardial and peritoneal coelomic cavities. (I-l) Sagittal section through 15 mm. pig embryo showing thickened anterior face of liver. This thickened anterior face of the liver later separates from the liver as the primary septum transversum (peritoneo-pericardial membrane). (1-2) Higher powered drawing to show condition of anterior face of liver shown in fig. 362, I-l. (J) Transverse section through thorax and pulmonary area of the body of a bird to show position of dorsal pulmonary diaphragm. (Redrawn from Goodrich, 1930, Studies on the Structure and Development of Vertebrates, Macmillan Co., Limited, London.) Observe position of liver lobes in relation to the heart. Compare with fig. 294, G-4 & G-5.



Fig. 362 — (Continued)

See legend on p. 860 .



(2) a larger caudal compartment, the peritoneal cavity, around the digestive viscera and urogenital structures.

This primary division of the early coelomic cavity is accomplished by the formation of:

1 ) The lateral mesocardia, and

2) the primary (primitive) septum transversum.

The two lateral mesocardia are formed previous to the development of the primitive septum transversum. Eventually the lateral mesocardia fuse in part to the dorsal edge of the transverse septum and become a part of it. The lateral mesocardia thus, in reality, represent the initial stage in the division of the general coelomic cavity. In consequence we shall consider the lateral mesocardia as important structures which enter into the formation of the primary transverse division of the embryonic body, but they should not be confused with the primitive septum transversum in a strict sense.

a. Lateral Mesocardia

The lateral mesocardia (fig. 362A-1, A-2) are formed as follows:

A lateral bulging or growth from the splanchnopleure at the caudal limits of the developing sinus venosus extends dorso-laterad on each side to meet a somewhat similar though smaller growth mediad of the somatopleural mesoderm. These growths form a bridge on each side across the coelomic cavity, extending dorso-laterad from the posterior lateral edges of the ventrally situated sinus venosus to the somatic wall. The area of union of this bridge on either side with the lateral body wall is the lateral mesocardium. The lateral mesocardia, in other words, represent the areas of juncture between the lateral body walls and the lateral extensions of the sinus venosus. The common cardinal veins or ducts of Cuvier join these right and left lateral extensions or horns of the sinus venosus in the substance of the lateral mesocardia. Anterior to the lateral mesocardia is the pericardial coelom, while posterior to them is the peritoneal coelom. The two passageways dorsal to the lateral mesocardia, on either side, are called the dorsal parietal recesses of His, while those ventral to the lateral mesocardia and on either side of the ventral mesentery and developing liver constitute the ventral parietal recesses of His (fig. 362A).

b. Formation of the Liver-Septum Tramversum Complex

1) Formation of Liver-Septum Complex through Modification of the Ventral Mesentery by Liver Outgrowth. As the liver rudiment in the shark, chick, pig, etc., grows ventrally and forward between the two splanchnopleural layers of the ventral mesentery, it expands the ventral mesentery laterally as the liver substance forms within the mesenchyme between the two splanchnic layers. The expanding liver substance eventually reaches the ventral and lateral




hepato duodenal


A. -3.

Fig. 363 (A-1, 2, 3). Diagrams showing the invasion of the peritoneal coelom around the liver and relations of septum transversum and diaphragm to the liver. (A-1) The peritoneal invasion separates the liver substance away from the lateral body wall and also from the anterior face of the liver itself. The separated, thickened, anterior face of the liver (see fig. 362, I-l and 1-2) forms the primary septum transversum (peritoneopericardial membrane). (A-2) The relation of the liver and other viscera to the secondary septum transversum formed by the addition of the dorsal closing folds (see fig. 362D) to the primary septum transversum. (A-3) This is a diagrammatic representation of conditions shown in B. Observe position of various ligaments associated with the liver. (B) Sagittal section through opossum embryo presenting relation of the liver to diaphragm. The ventral part of the diaphragm is the remodeled primary septum transversum. Observe that the inferior vena cava perforates the diaphragm. The area of attachment of the liver to the diaphragm is the coronary ligament, (The preparation from which this drawing was made was loaned to the author by Dr. J. A. McClain.) (C) Pericardioperitoneal opening below the esophagus in the shark, Squalus acanthias. (See also fig. 362D.) (D) Schematic diagram, dorsal view, of initial stage of devel oping pleural cavities in the mammal showing the anterior and posterior lateral body folds. The anterior lateral body fold gives origin to the pulmonary ridge or rudiment of the pleuropericardial membrane and the posterior lateral body fold forms most of the pleuroperitoneal membrane. Cf. fig. 362E. (E-H) Schematic diagrams showing later

stages in separation of pleural cavities in the mammal, viewed from the dorsal aspect. Observe that the pleuroperitoneal membrane is formed from two rudiments, viz., the posterior lateral body fold and a very small splanchnopleuric contribution (fig. 363F).












- pleural CAVIT



Fig. 363 — (Continued)

See legend on p. 864.

body wall, where it fuses with the somatopleure from the body wall. Since the lateral expansion of the developing liver is more rapid than its forward growth, the anterior face of the liver gradually becomes flattened in the area just below (ventral to) the lateral mesocardia and immediately posterior to the sinus venosus of the heart. The mesenteric tissue, covering the anterior face of the liver, then fuses with the more dorsally located, lateral mesocardia. A transverse division across the body is completed in this manner below the lateral mesocardia, and the ventral parietal recesses in consequence are closed. Passage from the pericardial cavity to the peritoneal (abdominal) cavity is now possible only by way of the pericardioperitoneal canals (dorsal parietal recesses) (fig. 362E).

Although liver-rudiment development in the embryo of the frog and in the embryos of other amphibians is precocious the essential procedure in the



formation of the primitive liver-septum transversum complex is similar to that described above.

2) Formation of the Liver-Septum Complex in the Human Embryo. In the

developing human embryo, medial growths on either side from the somatopleural mesoderm occur in the region caudoventral to the forming sinus venosus, and below the developing gut tube. In this way ,a primitive transverse septum is formed below the lateral mesocardia and between the entoderm of the gut and the caudal wall of the parietal pericardium (fig. 362F, G). This septum fuses with the lateral mesocardia and caudal wall of the parietal pericardium. However, when the evaginating liver rudiment grows ventrad and forward into the splanchnopleural tissue below the gut, it ultimately appropriates the previously formed transverse septum as its anterior aspect. Consequently, the general result of the two methods is the same, namely, the transverse septum in its earlier stages of development appears as the thickened anterior face of the liver associated with the lateral mesocardia (figs. 261 A; 362H, I).

c. Formation of the Primary Septum Transversum

After the liver-septum transversum complex has been established and the potential ventral parietal recesses are closed by either of the two methods described above, the next stage in the development of the primitive septum transversum is correlated with the forward expansion of the peritoneal coelom around the sides and anterior face of the liver. In doing so, the peritoneal coelom on either side of the liver extends anteriad and mesiad and thus becomes involved in a secondary separation of the liver from the lateral and ventral body wall and also from the anterior face of the liver itself which becomes the primary septum transversum (fig. 363 A, B). A separation does not occur in the area traversed by the veins passing from the liver to the sinus venosus or slightly dorsal to this area. Here the liver remains attached directly to the septum transversum and is suspended literally from it. This attaching tissue forms the coronary ligament of the liver. The ingrowth of the two coelomic areas on either side of and ventral to the liver, by apposition of the coelomic epithelium in the median plane, forms a secondary ventral mesentery of the liver. This secondary ventral mesentery or falciform ligament ties the liver to the mid-ventral area of the body wall and to the septum transversum. {Note: The terms primary septum transversum and peritoneopericardial membrane are synonymous.)

C. Coelomic Changes in Fishes, Amphibians, Reptiles, and Birds 1. In Fishes

In the adult shark, and fishes in general, the fully developed adult form of the septum transversum forms a complete partition between the pericardial cavity and the peritoneal cavity. In fishes the pericardial cavity in the adult fish, as in the embryo, extends laterally and ventrally to the body wall in a



fashion similar to that of the peritoneal cavity. Also, the heart continues to lie posterioventrally to the pharyngeal region in a manner very similar to that of the basic, embryonic body plan (fig. 294G-I).

In the formation of the adult, piscine, septum transversum from the primary transverse septum two membranous partitions are developed which close the dorsal parietal recesses or the openings above the lateral mesocardia. These partitions are called the dorsal closing folds and they arise as follows:

The splanchnopleural tissue on either side of the foregut, just anterior to the stomach rudiment and above the primitive septum transversum, forms a thin fold of tissue. This fold grows laterad and ventrad and fuses ultimately with the lateral mesocardium and the somatopleuric tissue, which overlies the common cardinal vein, as this vein travels caudo-ventrally along the body wall to reach the lateral mesocardium and the sinus venosus. As a result of this splanchnopleuric and somatopleuric fusion of tissues with the dorsal edge of the primary septum transversum a dorsal closing fold is formed on either side of the esophagus, and the two dorsal parietal recesses are obliterated, separating completely the pericardial cavity from the peritoneal cavity (fig. 362D). However, a small pericardioperitoneal opening may be left below the esophagus in the shark.

The secondary septum transversum thus formed is a thickened transverse partition, composed of two walls, an anterior pericardial wall and a posterior peritoneal wall, with a loose tissue layer between these two coelomic membranes. The liver is suspended from the peritoneal or caudal aspect of the septum transversum in the region of the coronary ligament, while the posterior end of the sinus venosus is apposed against the anterior or pericardial face of the transverse septum. The common cardinal and other converging veins of the heart utilize the substance of the septum transversum as a support on their way to the sinus venosus. The hepatic veins (the right and left, embryonic vitelline veins) pass through the coronary ligament on their journey to the sinus venosus.

2. In Amphibians, Reptiles, and Birds

The conversion of the primary septum transversum in amphibians, reptiles, and birds into the secondary or adult septum transversum occurs essentially as described above. A dorsal closing fold, obliterating the dorsal parietal recess on either side of the gut, is developed, although, in reptiles and birds, the inward growth and contribution of somatopleuric tissue overlying the common cardinal ridge is more important than in fishes in effecting this closure.

However, one must keep in mind an important fact, namely, that, in amphibia, reptiles and birds, there is an extensive caudal migration of the heart, septum transversum, and liver complex from their original cephalic position just posterior to the pharyngeal area. This caudal migration produces a condition in which the primary septum transversum and the dorsal membranes,



formed by the dorsal closing folds, are inclined to a great degree, with the ventral end of the primary septum transversum considerably more posterior in position than the dorsal edge of the dorsal membranes. Consequently, a secondary recess or pocket is formed on either side anterior and dorsal to the septum transversum. This secondary recess occurs on either side of the gut, and, into each of these recesses, a lung extends in many reptiles and in those amphibia which possess lungs. In this pocket also lie certain of the air sacs of birds. Thus, the general cavity back of the pericardioperitoneal membrane or secondary septum transversum (i.e., the primary septum transversum plus the two dorsal membranes, formed by the dorsal closing folds) is known as the pleuroperitoneal cavity in amphibia and many reptiles. In birds (see below), the respiratory part of the lung becomes enclosed dorsally near the vertebrae within a separate pleural cavity, separated from the peritoneal cavity by the dorsal diaphragm (fig. 362J). The thin air sacs of the bird’s lung (Chap. 14) project from the lung through the dorsal diaphragm into the peritoneal cavity and also into certain of the bones. In the turtle group, among the reptiles, a dorsal diaphragm is developed below each lung, segregating the lungs partly within dorsal cavities, thus simulating the bird condition.

D. Formation of the Coelomic Cavities in Mammals

In the mammalia, a pronounced caudal migration of the heart, liver, and developing diaphragm occurs. Also, as in birds, a further morphogenetic feature is present which results in the development of a pleural cavity for each lung in addition to the peritoneal and pericardial cavities present in fishes, amphibians, and reptiles. Thus it is that the development of two partitioning membranes on either side of the gut tube, the pleuropericardial membranes, which correspond to the dorsal closing membranes mentioned above, together with two additional membranes, the pleuroperitoneal membranes, are necessary to effect the division of the primitive splanchnocoelic coelom into the four main coelomic cavities in the Mammalia.

1. Formation of the Pleuropericardial Membrane

It so happens that the anterior cardinal vein develops slightly in advance of the posterior cardinal vein. As a result the common cardinal vein, which develops from the caudal end of the primitive anterior cardinal vein, travels along the lateral body wall in an inclined plane to reach the area of the lateral mesocardium and sinus venosus of the heart. This inclined pathway of the common cardinal vein is characteristic of the vertebrate embryo. As the common cardinal vein increases in size, a lateral ridge or elongated bulge is formed along the lateral body wall. This ridge projects inward into the coelomic cavity and inclines caudo-ventrally to reach the dorsal edge of the area of the primitive septum transversum (fig. 363D).

In the mammals, the mesonephric folds (ridges), in which the mesonephric



kidneys develop, are large and project downward into the coelomic cavity. The anterior ends of the mesonephric ridges continue along the lateral body wall on either side and follow an inclined plane antero-ventrally to the dorsal edge of the primitive septum transversum (fig. 363D). Two lateral body folds or ridges, which incline toward and fuse with the dorsal edge of the primitive septum transversum, are produced in this manner on either side. These folds are an anterior lateral body fold or ridge, overlying the common cardinal vein, and a posterior lateral body fold, which represents the antero-ventral continuation of the mesonephric ridge as it inclines ventrally to join the lateral edge of the primitive septum transversum (fig. 363D). A V-shaped pocket is formed between these two ridges. This pocket represents the primitive pleural cavity or pocket. The apex of this V-shaped pocket unites with the primitive septum transversum. As the lung buds grow out posteriorly below the foregut, each projects into a pleural pocket (fig. 363F).

The formation of the pleuropericardial membrane is effected by an ingrowth of tissue along the edge of the anterior, lateral body fold, the fold that overlies the common cardinal vein. This ingrowing tissue forms a secondary ridge, known as the pulmonary ridge, which continues to grow mesad below the developing lung until it reaches the splanchnopleure of the esophagus with which it fuses. A pleuropericardial membrane, in this way, is established which separates the pericardial cavity below from the pleural cavity above (fig. 363E-G). The pleuropericardial membranes probably arc homologous with the dorsal closing folds of the secondary septum transversum of the vertebrates below the mammals.

2. Development of the Pleuroperitoneal Membrane

As mentioned previously, the cephalic end of the mesonephric ridge projects forward and ventrad along the lateral body wall to unite with the primitive septum transversum to form the posterior, lateral body fold. The medial growth of this posterior, lateral body fold and ultimate fusion with a small splanchnopleural outgrowth, the splanchnopleural fold, forms a second partitioning membrane, the pleuroperitoneal membrane, which separates the pleural cavity from the general peritoneal cavity (fig. 363E-H). Contributions of the somatic mesoderm to the lateral body-fold tissue are significant in the formation of the pleuroperitoneal membrane. It is to be noted that the primitive pleural cavities of the mammalian embryo are small and dorsally placed, one on either side of the gut and dorsal to the pericardial cavity. Their later expansion is described below. To summarize the partitioning process of the primitive coelom in mammals, we find that the following membranes are formed:

( 1 ) the primary septum transversum,

(2) the two dorsal closing folds or pleuropericardial membranes, and

(3) two pleuroperitoneal membranes.

Fig. 364 (A). Transverse section of the thoracic area of opossum embryo showing the separation of the parietal pericardium from the lateral body walls by expanding pleural sacs. (The preparation from which this drawing was made was loaned to the author by Dr. J. A. McClain.) (B-1) Transverse section through lung buds and pleural




E. Development of Independent Pericardial Walls

1. The Arrangement of the Parietal Pericardial Wall in Fishes

The parietal pericardium of the fish embryo is fused with the lateral body wall. The caudal area of the sinus venosus is associated intimately with the anterior wall of the septum transversum. This condition is a primary one in all vertebrate embryos. It is retained in the adult fish.

2. Formation of an Independent Parietal Pericardial Wall

IN THE Chick

In the chick, two main processes occur in development which separate the septum transversum from the liver, and also the parietal pericardial membrane from the lateral body walls. These processes are:

(a) The peritoneal cavity on either side of the liver grows forward and separates the cardiac or anterior face of the liver from the posterior face of the septum transversum, with the exception of the area where the veins from the hepatic region perforate the septum. This process frees the septum transversum from the liver surface and permits it to function as a part of the pericardial sac as indicated in figure 294G-4; G-5.

(b) The extending peritoneal coelom not only separates the liver from the posterior face of the septum transversum, but it continues anteriad followed by the liver lobes along the ventral and lateral aspects of the body wall and splits the membranous pericardium away from the lateral body wall. Ventrally, a median septum unites the pericardium with the body wall (fig. 362J).

3. Formation of the Independent Parietal Pericardial Wall

IN Amphibians and Reptiles

A somewhat similar process to that described for the chick obtains in reptiles and, to a modified extent, in amphibia.

Fig. 364 — Continued

cavities of a 10 mm. pig embryo showing position of the primitive mediastinum. (B-2) Later mediastinal area development portraying adult position (black area) of the mediastinum. (Based on the cat.) Observe that fig. 364 (A) is an intermediate condition between figs. 364 (B-1) and 364 (B-2). (C) Probable origin of parts of the mammalian diaphragm. (D) The caudal migration of the septum transversum and developing diaphragm during development. 2-position = embryo of 2 mm.; 24-position = 24 mm. embryo. (Redrawn from F. P. Mall, 1910, Chap. 13, Vol. 1, Manual of Human Embryology, Lippincott, Philadelphia.) (E-H) Development of the mesenteries and omental bursa or lesser peritoneal cavity in the human. The cross-lined areas in H show areas of the mesentery which fuses with the body wall. The arrows in F-H denote development of the lesser peritoneal cavity.



4. Separation of the Parietal Pericardial Wall in Mammals

On the other hand, in the mammals, it is the pleural cavities, i.e., the pleural divisions of the splanchnocoelic coelom, which extend ventrally around the heart and thus separate the parietal pericardium from the thoracic body wall (fig. 364A and B) . Posteriorly, they separate the pericardium from the anterior face of the developing diaphragm (fig. 363B). The secondary condition of the mediastinum thus is established which extends dorsoventrally between the two pleural sacs (fig. 364B-2). It is to be observed that the medial walls of the pleural sacs fuse with the lateral walls of the pericardium by means of the connective tissue which forms between these two layers.

F. The Mammalian Diaphragm

The mammalian diaphragm is a musculotendinous structure, innervated by the phrenic nerve and developed from tissues around the gut, primary septum transversum, the two pleuroperitoneal membranes, and possibly also by contributions from the body wall. Study figure 364C. The exact origin of the voluntary musculature of the diaphragm is in doubt, but it is assumed to come from the cervical myotomes in the region of origin of the phrenic nerve, together with some invasion of muscle substance from the lateral body wall posterior to the cervical area. Successive caudal positions of the septum transversum and developing diaphragm, assumed during its recession in the body, are shown in figure 364D.

G. The Pulmonary Diaphragm or Aponeurosis of the Chick

The pulmonary diaphragm in the chick is a composite structure formed of two membranes which develop in a horizontal position in the dorsal region of the thoracic area below the lungs. Each of these two membranes fuses with the median mesentery and the lateral body wall and thus forms a partition separating the pleural cavities above from the peritoneal cavity below (fig. 362J). The development of this partitioning membrane is as follows:

In the four- to five-day chick as the lung buds grow out dorso-posteriad each lung bud pushes into a mass of mesenchyme which is continuous from the splanchnopleure around the esophagus to the dorsal region of the liver.

This connecting bridge of mesenchyme is the pleuro-peritoneal membrane and it extends from the region of the esophagus across the lower part of the lung bud tissue to the liver lobe on each side. The mesenchymal connection of this membrane with the liver then spreads laterally to unite with the lateral body wall. As a result, the pleural cavity above is shut off from the peritoneal cavity below. A continual growth dorsoposteriad of the pleuro-peritoneal membrane, and subsequent fusion with the dorsal body wall tissues, separates the pleural cavity completely from the peritoneal cavity. However, certain canals remain in this membrane for the passage of the air sacs (see Chapter 14) of the lungs. Striated musculature from the lateral body wall grows into



the pleuro-peritoneal membrane on either side and converts it into a muscular structure. These two muscular partitions thus form the pulmonary diaphragm.

H. The Omental Bursa

In all gnathostomous vertebrates, the mesogastrium is prone to form a primitive pocket, associated with the rotation of the stomach to the right. This pocket is quite prevalent in most gnathostomous embryos from the elasmobranch fishes to the mammals and is known as the primitive omental bursa. In mammals, the omental bursa is highly developed, and it gives rise to the lesser peritoneal cavity, retaining its connection with the greater peritoneal cavity by means of the foramen of Winslow. The lesser peritoneal cavity in the cat is extensive, filling the entire inside of the omental sac. In the human, however, the distal part of the lesser peritoneal cavity is reduced by the fusion of the omental layers. Though a rudimentary omental bursa is formed in the early embryonic condition of elasmobranch fishes (sharks), it soon disappears, so that, in the adult fish, the omental bursa is nonexistent. Figure 364E~H presents various stages in the development of the omental bursa in the human embryo.

I. The Formation of Various Ligaments in the Stomach-Liver Region

Ligaments are those specializations of the peritoneal tissue which unite various organs with each other or with the body wall.

1. The Gastro-hepatic and Hepato-duodenal Ligaments. These structures are derivatives of the ventral mesentery between the stomach-duodenal area and the liver. The gastro-hepatic ligament ties the stomach and liver together while the hepato-duodenal ligament unites the duodenum with the liver.

2. The Coronary Ligament of the Liver. This is the tissue which unites the liver with the caudal face of the septum transversum and in mammals with the later developed diaphragm. Its development is described on page 866.

3. The Falciform Ligament of the Liver. This unites the liver in the median plane to the ventral body wall and to the septum transversum or diaphragm.

4. The Gastro-splenic Ligament suspends the spleen from the stomach and it represents a modification of the mesogastrium (see Chapter 17).

(Note: Ligamentous structures associated with the reproductive organs are described in Chapter 18.)


Goodrich, E. S. 1930. Chap. XU in Studies on the Structure and Development of Vertebrates. Macmillan and Co., London.

Mall, F. P. 1910. Chap. 13, Vol. I, Manual of Human Embryology, Lippincott, Philadelphia.


Tke Developing EnJ^ocrine Glands and Tlieir PossiLle Relation to Definitive Body Formation and tlie Differentiation of Sex

A. Introduction

B. Morphological features and embryological origin of the endocrine glands

1. Pancreas

2. Pituitary gland (hypophysis cerebri)

a. Anterior lobe

b. Posterior lobe

c. Pars intermedia

3. Thyroid gland

4. Parathyroid glands

5. Thymus gland

6. Pineal body

7. Adrenal (suprarenal) glands

8. Gonads

C. Possible influence of endocrine secretions on the development of definitive body form

1. Thyroid and pituitary glands and anuran metamorphosis

2. Tliyroid and pituitary glands in relation to the development of other vertebrate embryos

a. Chick

1) Thyroid gland

2) Pituitary gland

b. Mammal

1) Thyroid gland

2) Pituitary gland

c. Fishes

3. General conclusions relative to the influence of the thyroid and pituitary glands in vertebrate embryology

D. Possible correlation of the endocrine glands with sex differentiation

1. Differentiation of sex •

a. General sex features in the animal kingdom

b. Chromosomal, sex-determining mechanisms

c. Possible influence of the sex field in sex determination

2. Influence of hormones on the differentiation of sex

3. General summary of the factors involved in sex differentiation in the vertebrate group




A. Introduction

The endocrine glands are those glands which produce hormonal secretions. The term hormone is derived from a Greek word meaning to stimulate or to stir up. Selye in 1948 (p. 11) defined hormones as physiologic, organic compounds produced by certain cells for the sole purpose of directing the activities of distant parts of the same organism.”

The endocrine organs may be separated into two main groups:

(1) purely endocrine glands, and

(2) mixed endo-exocrine glands.

Purely endocrine glands have as their sole function the production of hormones. Under this heading are included the pituitary (hypophysis), thyroid, parathyroid, pineal, adrenal (suprarenal), and thymus glands.

Mixed endo-exocrine glands are exemplified by the pancreas, liver, duodenum, and reproductive organs. Parts of these organs are purely exocrine, e.g., the pancreas where pancreatic juice is produced by the acinous cells but which elaborates, at the same time, insulin from the islets of Langerhans. The liver elaborates the exocrine secretion, bile, which is discharged through the bile ducts and, concurrently, manufactures the antipernicious-anemia factor which is dispensed into the blood stream directly. The duodenum produces digestive substances and also secretin. Secretin is elaborated by the epithelial lining cells of this area, and it stimulates the pancreas to secrete its pancreatic juice.

Relative to their secretory activities all endocrine glands have this physiomorphological feature in common: They discharge the hormonal or endocrine substance directly into the blood stream without the mediation of a duct system. Endocrine glands, therefore, are distinguished by this process from exocrine glands, which exude the secretory product into a duct system from whence the secretion passes to the site of activity.

B. Morphological Features and Embry ological Origin of the Endocrine Glands

1. Pancreas

The islets of Langerhans are small masses of cells or islands scattered among the acini (alveoli) of the general pancreatic tissue. The pancreatic islets appear to arise as specialized buds from the same entodermal cords which give origin to the alveoli. The islets separate early from the entodermal cords and produce isolated cellular cords. Blood capillaries form a meshwork within these cords of cells (figs. 295G; 365A). Their secretion, insulin, is concerned with sugar metabolism and prevents the malfunction known as diabetes.

Pancreatic islets are found extensively in the vertebrates and generally are



























Fig. 365. The pancreatic islets and pituitary gland. (A) Origin of islet tissue from developing pancreatic ducts and acini. 1 == young bud; 5 = older bud. (Modified from Arey, ’46, Developmental Anatomy, Philadelphia, Saunders.) (B-E) Diagrams of pituitary gland conditions in Petromyzon (B), Rana (C), Reptile (D), and Man(E). (Modified from Neal and Rand, 1939, Chordate Anatomy, Philadelphia, Blakiston.) (F) Origin of Rathke’s pouch material from inner layer of epidermal ectoderm in early tadpole of Rana. (G-I) Developmental stages of hypophysis in human embryo.

associated with the pancreas. In some teleost fishes, the two glands are separated although both are derived from the entoderm. The pancreatic islets are classified as belonging to the solid, non-storage type of endocrine gland.

2. Pituitary Gland (Hypophysis Cerebri)

Previous to the latter part of the last century, the function of the pituitary gland was presumed to be one of mucous secretion, hence the name pituitary from the Latin, pituita, a nasal secretion. It was so regarded by Vesalius in 1543. The English anatomist, Willis, believed that the pituitaly gland secreted the cerebrospinal fluid.

The pituitary gland (fig. 365E and I) is composed of three main parts as follows:

a. Anterior Lobe

The anterior lobe (pars anterior) is composed of two subdivisions:

( 1 ) a large anterior lobe (pars distalis), and

(2) a smaller glandular mass (pars tuberalis).



b. Posterior Lobe

The posterior lobe (lobus nervosus, pars neuralis) is derived from the distal part of the infundibulum.

c. Pars Intermedia

The pars intermedia or intermediate lobe is associated closely with the posterior lobe but has the same embryonic origin as the pars distalis and pars tuberalis of the anterior lobe.

In Petromyzon fiuviatilis, the hypophysis is a flat, tube-like organ attached to the infundibular evagination of the floor of the diencephalon. The anterior lobe is represented by the hypophyseal duct which ends blindly below the infundibulum. From this duct are proliferated the cells of the intermediate lobe (tig. 365B). The pituitary gland shows great similarity, in all higher vertebrates, being composed of three main parts, viz., pars anterior, pars intermedia, and pars posterior (fig. 365C-E). However, in the chicken, whale, manatee, and armadillo, the intermediate lobe is missing (Selye, ’48).

The pars anterior and the pars intermedia of the pituitary gland develop from Rathke’s pouch as evaginations of the middorsal area of the stomodaeal pocket, although in the frog Rathke’s pouch develops precociously from the so-called neural ectoderm above the stomodaeal invagination (fig. 365F-I). Rathke’s pouch gradually comes into contact with the ventrally directed infundibular evagination from the diencephalon. The distal part of the infundibular evagination forms the pars neuralis, while Rathke’s pouch differentiates into the pars distalis, pars intermedia, and pars tuberalis.

3. Thyroid Gland

The thyroid gland (fig. 366B) was described first in 1656 by Thomas Wharton, the English anatomist, who called it the thyroid gland because of its association with the thyroid or shield-shaped cartilage of the larynx.

After about 50 years of work by many observers on the thyroid gland and its activities, the crystalline form of the secretory principle of the thyroid gland was isolated by Kendall in 1919, and he called it thyroxine. This compound contained 65 per cent of iodine by weight and its empirical formula was subsequently determined as C, 5 H„ 04 Nl 4 .

One of the thyroid’s functions is to govern carbohydrate metabolism, and, in general, the gland controls the basal metabolism of the animal together with growth processes. In man and the cat, the thyroid gland is in the form of two lateral lobes, located on the ventro-lateral aspect of the thyroid cartilage of the larynx, the two lobes being joined by an isthmus. In birds, there are two glands, both being located within the thoracic cavity; in fishes, including the Cyclostomes, the thyroid is an unpaired structure and is to be found generally between and near the posterior ends of the lower jaws. The gland, therefore, is a constant feature of all vertebrates.



PARATHYROID E parathyroid ur









THYMUS gland





thyroid follicle

Fig. 366. Thyroid, parathyroid, and thymus glands in human embryo. (A) The loci of origin of thyroid, parathyroid, thymus, and ultimobranchial bodies. (B) Late Stage (somewhat abnormal) of thyroid, parathyroid, and thymus gland development in human. (C) Early stage of thyroid follicle differentiation. (D) Later stage of thyroid follicle differentiation.

In the embryos of all vertebrates the thyroid gland appears as a pharyngeal derivative. In the human as in fishes and amphibia (Lynn and Wachowski, ’51), it arises as a midventral outpocketing of the anterior pharyngeal floor. In the human embryo, this outpocketing occurs between the first and second branchial pouches at about the end of the fourth week of development (fig. 3 66 A). Its point of origin is observable during later development as a small indentation, the foramen caecum, in the region between the root and body of the tongue (fig. 285). It is a bilobed evagination which soon loses its connection with the pharyngeal floor and migrates caudally to the laryngeal area where it differentiates into a double-Iobed structure, connected by a narrow bridge of thyroid tissue, the isthmus. Occasionally, a persistent thyroglossal duct, connecting the foramen caecum with the thyroid gland, remains (fig. 366B). While the thyroid rudiment migrates posteriad, the post-branchial (ultimobranchial) bodies, which take their origin from the caudal margin of the fourth branchial pouch, become incorporated within the thyroid tissue.



The significance of this incorporation is unknown, and evidence of functional thyroid tissue, being derived from the post-branchial body cells, is lacking.

When the cellular masses of the developing thyroid gland reach the site of the future thyroid gland, the cells multiply and break up into cellular strands, surrounded by mesenchyme and blood vessels (fig. 366C). These strands in turn break up into small, rounded, bud-like masses of epithelial cells, the young thyroid follicles (fig. 366D). During the third month of development in the human, colloidal substance begins to appear within the young thyroid follicles. The colloid increases during the fourth month, and the surrounding cells of the follicle appear as a single layer of low columnar cells. Each thyroid follicle as a whole assumes the typical appearance of a functioning structure. Blood capillaries ramify profusely between the respective follicles.

The colloidal substance within each thyroid follicle presumably represents stored thyroid secretion, and the thyroid gland is regarded, therefore, as a “storage type” of endocrine gland. The theory relative to thyroid gland function is set forth that the follicle cells may secrete directly into the capillaries and, hence, into the blood stream, or the secretion may be stored as colloid within the follicles. Later this reserve secretion in the form of colloid may be resorbed by the cells in times of extreme activity and passed on into the region of the capillaries. In certain instances, e.g., dog and rat, individual thyroid follicles may be lined with stratified squamous epithelium (Selye, ’48, p. 695).

In the larvae of the cyclostome, Petromyzon, the so-called endostyle is lined with rows of mucus-secreting cells, alternating with ciliated cells. This endostylar organ becomes transformed into the thyroid gland upon metamorphosis. A localization of iodine in certain of the endostylar cells in the larva has been demonstrated (Lynn and Wachowski, ’51, p. 146).

4. Parathyroid Glands

The parathyroid glands in man are four, small, rounded bodies, located along the dorsal (posterior) median edges of the two thyroid lobes of the thyroid gland (fig. 366B). Unlike the storage type of endocrine gland, such as the thyroid gland with its follicles, the parathyroids contain no follicles and, therefore, represent the solid type of endocrine gland. Blood capillaries ramify through its substance which is composed of closely packed masses of polyhedral epithelial cells, arranged in small cords or in irregular clumps. Two main cell types are present in mammals, the chief or principal cells with a clear cytoplasm and the oxyphil cells whose granules stain readily with acid stains. The chief cells are common to all vertebrate parathyroids and thus may represent the essential cellular type of the parathyroid gland (Selye, ’48, p. 540).

The removal of the parathyroid glands results in a reduction of the calcium content of the blood, muscular tetany, convulsions, and ultimate death. The



parathyroid glands in some way regulate calcium metabolism to keep the calcium content in the blood stream at its proper level.

Parathyroid structures may be present in fish (Selye, ’48), but it is generally believed that true parathyroid tissue is confined to the Tetrapoda. Two parathyroid glands on each side are found in most urodeles and other amphibia, and in reptiles. The birds have relatively large parathyroid glands, attached to the two thyroid glands located in the thoracic cavity. All mammals possess parathyroid glands which, in some instances, are located internally within the thyroid gland as well as externally. Accessory parathyroid glands, apart from the two parathyroids attached to the thyroid gland, are found in rats and mice and, consequently, may not be disturbed if the thyroid gland is removed in these rodents.

The parathyroid glands arise in the human embryo from proliferations of the dorso-lateral walls of the third and fourth branchial pouches (fig. 366A). The parathyroids which arise from the third pair of pouches are known as parathyroids III, while those from the fourth pair of branchial pouches are called parathyroids IV. Parathyroids III arise in close proximity to the thymusgland rudiments (fig. 366A). However, it is to be observed that the thymus rudiments arise from the ventral aspect of the third pair of pouches. The parathyroid-III rudiments move caudally with the thymus gland rudiments and come to lie in relation to the lateral lobes of the thyroid, posterior to parathyroids IV which take their origin in close relation to the post-branchial (ultimobranchial) bodies (fig. 3 66 A and B).

Parathyroids IV appear to be a constant feature of all Tetrapoda. In those species having but two parathyroids, it is probable that their origin is from the fourth branchial pouches.

5. Thymus Gland

The thymus gland or “throat sweetbread” (the pancreas is referred to commonly as the “stomach sweetbread”) lies in the anterior portion of the thoracic cavity and posterior neck region (fig. 366B). In some cases, it may extend well along in the neck region toward the thyroid gland. In the thoracic area, it lies between the two pleural sacs, that is, within the mediastinum, and reaches as far caudally as the heart. Histologically, it is composed of two parts:

( 1 ) a cortex and

(2) a medulla.

The cortex contains masses of thymocytes or lymphocyte-like cells, while the medulla contains thymocytes, reticular cells, and the so-called Hassall’s corpuscles, composed of stratified, squamous, epithelial cells.

In man, the thymus gland arises from the ventral portion of the third



branchial pouches during the sixth week. These epithelial derivatives of the third branchial pouch become solid masses of cells which migrate posteriad into the anterior thoracic area.

The thymus gland is found in all vertebrates, but its morphology is most variable. In birds, it is situated in the neck region in the form of isolated, irregular nodules. The bursa of Fabricius, previously mentioned (Chap. 13) as an evagination in the cloacal-proctodaeal region of the chick, is a “thymuslike organ” (Selye, ’48, p. 681 ). Thymus glands in reptiles are located in the neck region, and, in amphibians the two thymus glands lie near the angle of the jaws. In fishes several small, thymus-gland nodules arise from the dorsal portions of the gill pouches and come to lie dorsal to the gill slits in the adult.

The function of the thymus gland is not clear. It appears to have some relationship to sexual maturity. (For thorough discussion, see Selye, ’48, Chap. IX.)

6. Pineal Body

The pineal gland appears to have been first described by Galen, the Greek scientist and physician (130-ca.200 A.D.), who believed it to function in relation to the art of thinking. Descartes (1596-1650) considered it to be the “seat of the soul.”

During development, two fingerlike outgrowths of the thin roof of the diencephalon of the brain occur in many vertebrates, namely, an anterior paraphysis or parietal organ, and a more posteriorly situated epiphysis. In certain Cycles tomes (Petromyzon), the posterior pineal body or epiphysis is associated with the formation of a dorsal or pineal eye, while the anterior pineal organ or paraphysis forms a rudimentary eyelike structure. In Sphe nodon and in certain other lizards, the paraphysis or anterior pineal evagination develops an eyelike organ. Also, in various Amphibia (frogs; Ambystoma) rudimentary optic structures arise from the fused epiphyseal and paraphyseal diverticula. In consequence, we may assume that a primary function in some vertebrates of the dorsal, median pineal organs is to produce a dorsal, lightperceiving organ. In certain extinct vertebrates, a fully developed median dorsal eye appears to have been formed in this area.

On the other hand, the epiphysis (fig. 366A) in some reptiles, in birds and in mammals has been interpreted as a glandular organ. Various investigators have suggested different metabolic functions. However, an endocrine or essential secretory function remains to be demonstrated. (Consult Selye, ’48, p. 595.)

Many types of cells enter into the structure of the pineal gland. Among these are the chief cells, which are large and possess a clear cytoplasm. Nerve cells and neuroglial elements also are present. Various other cell types possessing granules of various kinds in the cytoplasm are recognized.



7. Adrenal (Suprarenal) Glands

The adrenal bodies are associated, as the name implies, with the renal organs or kidneys. In fishes, definite adrenal bodies are not present, but cellular aggregates, corresponding to the adrenal cells of higher vertebrates, are present and associated with the major blood vessels.

In man and other mammals, the adrenal body is composed of:

(1) an outer, yellow-colored cortex and

(2) an inner medullary area.

The medulla contains the chromaffin cells — cells which have a pronounced affinity for chromium salts, such as potassium dichromate, which stain them reddish brown and produce the so-called ‘‘chromaffin reaction.”

The hormone, secreted by the medulla, is adrenaline (epinephrine). It has marked metabolic and vasoconstrictor effects. The smooth muscle tissue of the arrector pili muscles associated with the hairs in mammals contract and raise the hair as a result of adrenaline stimulation.

The morbid state, known as Addison’s disease and named after the English physician, Thomas Addison, who first described this fatal illness, arises from decreased function of the adrenal cortex. Various types of hormones have been discovered which arise from the cortical layer of the adrenal body, and a large number of steroid substances have been isolated from this area of the adrenal gland (Selye, ’48, p. 89). In fishes, the cortical cell groups are isolated from those of the medulla, and, in the elasmobranch fishes, the cortex forms a separate organ. Its removal may be effected without injury to the medulla but with resulting debility, ending in death.

Embryologically, the adrenal cortex and medulla take their origin from two distinct sources. The cortex arises as a proliferation of the dorsal root of the dorsal mesentery in the area near the anterior portion of the mesonephric kidney and liver on either side (fig. 367A, B). These two proliferations give origin to two cortical masses, each lying along the anterior mesial edge of the mesonephric kidney. Further growth of these masses produces two rounded bodies, the adrenals (suprarenals), lying between the anterior portions of the mesonephric kidneys (figs. 3 A and B; 367B) and later in relation to the antero-mesial portion of the metanephric kidneys (fig. 3B-E). After the cortical masses are established, the chromaffin cells invade them from the medial side (fig. 367C). The potential chromaffin cells migrate from the sympathetic ganglia in this area. Upon reaching the site of the developing adrenal gland they move inward between the cortical cells to the center of the gland where they give origin to the medulla. With the diverse embryological origins of the cortex and the medulla, it is seen readily why two separate glandular structures are present in lower vertebrates.

In man and other mammals, a later developed secondary cortex is laid down around the primary cortex. The primary cortex, characteristic of fetal



| j 9 j < 1

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1 ^* ' ^ '


-aortic wall




OF adrenal gland A-:



Fig, 367. Differentiation of the adrenal (suprarenal) body. (A) Early stage in proliferation of adrenal cortical primordium from coelomic epithelium. (B) Later stage of cortex, forming rounded masses associated with cephalic ends of mesonephros. The anterior end of the mesonephros lies between the adrenal body and lateral wall of the coelom. (Compare fig. 3H and B.) (C) Cells from sympathetic ganglia penetrating

medial side of primitive cortical tissue of adrenal body to form chromaffin cells of adrenal medulla.

life, then comes to form the “inner cortical zone” or androgenic zone (Howard, ’39).

8. Gonads

The developing gonads were described in Chapter 18, and their hormonal functions were outlined in Chapters 1 and 2.

C. Possible Influence of Endocrine Secretions on the Development of Definitive Body Form

1. Thyroid and Pituitary Glands and Anuran Metamorphosis

One of the earlier studies in this field of development was that by Gudernatsch (’12 and ’14) which showed that mammalian thyroid gland fed to anuran, and urodele larvae stimulated growth, differentiation, and metamorphosis. In a later series of studies by Allen (see Allen, ’25, for references and review) and by Hoskins (’18 and ’19), it was demonstrated that the removal of the thyroid gland in young tadpoles of Rana and Bufo prevents metamorphosis from the larval form into that of definitive body form (i.e.,



the adult body form). Similar results were obtained as a result of hypophysectomy (i.e., removal of the hypophysis). (See Allen, ’29, and Smith, ’16 and ’20. ) The work of these observers clearly demonstrates that the thyroid and pituitary glands are instrumental in effecting the radical transformations necessary in the assumption of definitive body form in the Anura.

2. Thyroid and Pituitary Glands in Relation to the Development of Other Vertebrate Embryos

a. Chick

1) Thyroid Gland. Studies relative to the possible effect of the thyroid gland upon the developing chick embryo are complicated by the fact that the yolk of the chick egg is composed of many other factors besides fats, proteins, and carbohydrates. The yolk is a veritable storehouse for vitamins and for thyroid, sex, and possibly other hormones. Just what effect these substances have upon development is problematical. Some experiments, however, have been suggestive. Wheeler and Hoffman (’48, a and b), for example, produced goitrous chicks and retarded the hatching time of chicks from eggs laid by hens which were fed thyroprotein. Thyroprotein feeding seemingly reduced the amount of thyroid hormone deposited in the egg with subsequent deleterious effects upon the developing chicks. In normal development, the thyroid gland of the chick starts to develop during the third day and produces follicles which contain colloid by the tenth and eleventh days of incubation. Furthermore, Hopkins (’35) showed that thyroids from chick embryos of 10 days of incubation hastened metamorphosis in frog larvae. From days 8 to 14 the chick embryo undergoes the general changes which transform it from the larval form which is present during incubation days 6 to 8 into the definitive body form present at the beginning of the third week of incubation.

The foregoing evidence, therefore, while it does not demonstrate that thyroid secretion actually is being released by the developing thyroid gland into the chick’s blood stream, does suggest that the thyroid gland may be a factor in chick development and differentiation. If the chick’s thyroid gland is secreting the thyroid hormone into the chick’s blood stream during the second week of the incubation period, it is evident that the developing chick during the period when it is assuming the definitive body form has two sources of thyroid hormone to draw upon:

( 1 ) that contained within the yolk of the egg and

(2) that produced by its own thyroid gland.

2) Pituitary Gland. Relative to the development of the pituitary gland in the chick, Rahn (’39) showed that the anterior lobe develops both acidophilic and basophilic cells by the tenth day of incubation. Also, Chen, Oldham, and Ceiling (’40) demonstrated that the pituitary of chicks from eggs incubated



for five days possessed a melanophore-expanding principle when administered to hypophysectomized frogs.

This general evidence, relative to the developing pituitary gland in the chick, suggests that the cells of the pituitary gland may be active functionally during the latter part of the first week and during the second week of incubation. If so, the pituitary gland may be a factor in inducing the rapid growth and changes which occur during the second week of incubation. It suggests further, that a possible release of a thyrotrophic principle may be responsible for the presence of colloid within the developing thyroid follicles during the second week of incubation.

b. Mammal

As in the chick, the developing embryo of the placental mammal is in contact with hormones from extraneous sources. Hormones are present in the amniotic fluid, while the placenta is the seat of origin of certain sex and gonadotrophic hormones. Also, the maternal blood stream, which comes in contact with embryonic placental tissues, is supplied with pituitary, thyroid, adrenal, and other hormonal substances. This general hormonal environment of the developing mammalian embryo complicates the problem of drawing actual conclusions relative to the effect of the embryo’s developing endocrine system upon the differentiation of its own organ systems and growth. Nevertheless, there is circumstantial evidence, relating to possible activities of the developing, embryonic, endocrine glands upon development.

1) Thyroid Gland. Colloid storage within the follicles of the developing, human, thyroid gland is evident at 3 to 4 months. In the pig embryo, Rankin (’41 ) detected thyroxine and other iodine-containing substances in the thyroid at the 90-mm. stage, and Hall and Kaan (’42) were able to induce metamorphic effects in amphibian larvae from thyroids obtained from the fetal rat at 18 days. The foregoing studies suggest that the thyroid gland is able to function in the fetal mammal at an early stage of development. (For further references, consult Moore, ’50.)

2) Pituitary Gland. Similarly, in the pituitary gland, granulations within the cells of the anterior lobe are present in the human embryo during the third and fourth months (Cooper, ’25). Comparable conditions are found in the pituitary of the pig from 50 to 170 mm. in length (Rumph and Smith, ’26).

c. Fishes

The relationship between the thyroid and pituitary glands in the development of fishes is problematical. There is evidence in favor of a positive influence of endostylar cells and of the cells of the developing thyroid gland in the transformation of the ammocoetes larva of the cyclostome, Petromyzon, into the definitive or adult body form. Similar evidence suggests a thyroid activity relationship in the transformation of the larvae of the trout and



the bony eel. However, this evidence is not indisputable, and more study is necessary before definite conclusions are possible. (Consult Lynn and Wachowski, ’51, for discussion and references.)

3. General Conclusions Relative to the Influence of the Thyroid and Pituitary Glands in Vertebrate Embryology

These conclusions are:

(a) Positive activities of the thyroid and pituitary glands are demonstrated in the transformation of the larval form into the definitive or adult form in the Anura.

(b) Suggestive evidence in favor of such an interpretation has been accumulated in fishes.

(c) Circumstantial evidence, relative to the possible activities of the thyroid and pituitary glands during the period when the embryos of the chick and mammal are transforming into the adult form, is present. With the evidence at hand, however, it is impossible to conclude definitely that these glands are a contributing factor to a change in body form (metamorphosis) in chick and mammalian embryos (fig. 256).

D. Possible Correlation of the Endocrine Glands with Sex Differentiation

1. Differentiation of Sex a. General Sex Features in the A nimal Kingdom

Many animal groups are hermaphroditic, that is, both sexes occur in the same individual. Flatworms, roundworms, oligochaetous annelids, leeches, many mollusks, and certain fishes are representatives of this condition, whereas most vertebrates, insects, and echinoderms are bisexual. If one examines the developing gonads in insects or vertebrates, it is evident that, fundamentally, the potentialities for both sexes exist in the same individual. As observed previously (Chap. 18), the early gonad is bipotential in most vertebrates, and two sets of reproductive ducts are formed. As sex is differentiated, the gonadal cortex and the Mullerian duct assume dominance in the female, while the gonadal medulla and Wolffian duct become functional if the animal is a male. Generality, therefore, gives way to specificity. Conditions thus are established in the developing reproductive system, similar to the generalized conditions to be found in other systems. If we take into consideration the fact that in a large number of animals both sexes are present in a functional state in one individual and in many bisexual species both sexes are present in a rudimentary condition in the early embryo, we arrive at the conclusion that both sexes are fundamentally present in a large majority of animal species. Sex, therefore, tends to be an hermaphroditic matter among many species of animals. The problem of sex differentiation, consequently, resolves itself into this: Why do both sexes emerge in the adult condition in a large number of



animals, whereas in the development of many other animal species, only one of the two sex possibilities becomes functional?

b. Chromosomal, Sex-determining Mechanisms

A considerable body of information has been obtained which demonstrates a fundamental relationship between certain chromosomes and sex determination. The general topography of chromosomal sex-determining mechanisms has been established for a large number of species. A pair of homologous chromosomes, the so-called sex chromosomes, apparently have become specialized in carrying the genic substances directly concerned with sex determination. In many species, the members of this pair of sex-determining chromosomes appear to be identical throughout the extent of the chromosomes in one of the sexes. In the other sex, on the other hand, the two sex-determining chromosomes are not identical. When two identical chromosomes are present in a particular sex, that sex is referred to as the homogametic sex, for the reason that all of the gametes derived from this condition will possess identical sex chromosomes. However, that sex which possesses the two dissimilar chromosomes is called the heterogametic sex for it produces unlike gametes, Often the heterogametic condition is represented by one chromosome only, the other chromosome being absent. If under the above circumstances the normally appearing chromosome is called X, and the deleted, diminutive or strangely appearing chromosome is called Y, while the chromosome which is absent be designated as O, we arrive at the following formula:

XX = the homogametic sex and either XY or XO = the heterogametic sex. In many (probably in most) animal species the male is the heterogametic sex (fig. 36^A~C).

In some animal groups, however, such as the butterflies, the moths, possibly the reptiles, the birds, some fishes, and probably urodele amphibia, the female is the heterogametic sex, and the male is homogametic. In these particular groups, many authors prefer to use the designation ZZ for the homogametic sex (i.e., the male) and ZO or ZW for the female or heterogametic sex. The sex-determining mechanism in these groups, according to this arrangement, will be ZZrZW or ZZ:ZO (fig. 368D).

In endeavoring to explain the action of these chromosomal mechanisms, one of the underlying assumptions is that the genic composition of the chromosomes actively determines the sex. For example, in cases where the female sex is homogametic it is assumed that the X-chromosome contains genes which are female determining; when two (or more) X’s are present, the female sex is determined automatically. When, however, one X-chromosome is present, the determining mechanism works toward male determination. In those species where the female sex is the heterogametic sex it may be assumed that the Z-chromosome (or X-chromosome, depending upon one’s preference) contains genes which are male determining. When only one of these Z-chromo



Fig. 368. The sex chromosomes in man, opossum, chick, and Drosophila; parabiotic experiments in Amphibia. (A) Late primary spermatocyte in human. (A') First maturation spindle in human spermatocyte. (Redrawn from Painter, ’23, J. Exper. Zool., 37.) (B) Dividing spermatogonium in opossum testis. (B') First maturation spindle

in spermatocyte of opossum. (Redrawn from Painter, ’22, J. Exper. Zool., 35.) (C)

Sex chromosomes in female Drosophila. (C') Sex chromosomes in male Drosophila. (Redrawn from Morgan, Embryology and Genetics, 1934, Columbia University Press, N. Y., after Dobzhansky.) (D) Sex chromosomes in common fowl, male. (D') Sex chromosomes in common fowl, female. (Redrawn from Bridges, 1939, Chap. 3, Sex and Internal Secretions, edited by Allen et al., Baltimore, Williams and Wilkins, after Sokolow, Tiniakow, and Trofimov.) (E-G) Diagrams illustrating the spreading of gonadal substances in frogs, toads, and salamanders. In toads, E, the gonadal influences (antagonisms) are evident only when the gonads actually are in contact. In the frogs, F, the range of influence is wider but its effect falls off peripherally. Figure G represents the condition in newts and salamanders. It is evident that in this group, some substance is carried in the blood stream which suppresses the gonads in the two females as indicated in the diagram. (Redrawn and modified slightly from Witschi, 1939, Chap. 4, Sex and Internal Secretions, edited by Allen et al., Baltimore, Williams and Wilkins.)

somes is present the developmental forces swing in the direction of the female sex. Sex, from this point of view, is determined by a genic balance, a balance which in turn is governed by the quality of certain genes as well as the quantitative presence of genes. (For detailed discussion consult Bridges, ’39, and White, ’48.)



c. Possible Influence of the Sex Field in Sex Determination

Two gonadal sex fields, the cortical field and the medullary field, are present in the early vertebrate gonad in amphibians, reptiles, birds, and mammals. This condition is true also of many fishes. Sex differentiation primarily is a question as to which one of these fields will assume dominance. During development in various instances, sex differentiation is clearly the result of only partial dominance on the part of one sex field, the other field emerging partly or almost completely. As a result, various types of intersexes may appear. For example, in the male toad, Bidder’s organ at the anterior part of the testis represents a suppressed cortical or ovarian field, held in abeyance by the developing testis. Surgical removal of the two testes permits the cortical field or Bidder’s organ to become free from its suppressed state. As a result, functional ovaries are developed, and the animal reverses its sex, becoming a functional female (Witschi, ’39).

One of the classical examples which demonstrates the dependence of the developing sex field upon surrounding environmental factors is the freemartin. The freemartin appears in cattle when twins of the opposite sex develop in such a manner that an anastomosis or union of some of the fetal blood vessels occurs (Lillie, ’17). Under these circumstances the female twin always experiences a transformation in the direction of maleness in the gonad and sex ducts. In those instances of freemartin development where the cortical field of the developing ovary is suppressed and the medullary area is hypertrophic, a partial or fairly well-developed testis may be formed. Under these conditions it is presumed that some substance is elaborated within the medullary field of the developing gonad of the male twin which enhances the development of the similar field in the freemartin ovary and suppresses, at the same time, the cortical field. The development of fully differentiated gametes (i.e., sperm) in the freemartin “testis” has not been demonstrated, but, on the whole, the more normally developed freemartin testis shows conditions at the time of birth which are comparable to a similar gonad of the normal male at about the same age, with the questionable presence or absence of very young germ cells. Gametogenesis in the developing testis of the bull occurs after birth. Consequently, the development of gametes in the freemartin of cattle cannot be ascertained because the freemartin gonad remains in the position of the normal ovary and does not descend into the scrotum as it does in the male (Willier, ’21). A scrotal residence (Chap. 1) is necessary for spermatogenesis in all males, possessing the scrotal condition.

A particularly interesting case of intersexuality, resulting from the lack of complete supremacy on the part of one sex field, is shown in the fowl described by Hartman and Hamilton (’22). A brief resume of its behavior and anatomy, as described by the authors, is presented herewith.

The bird was hatched as a robust chick and developed into an apparently normal Rhode Island Red pullet. The following spring the comb and wattles began to



enlarge, and the bird after a few abortive attempts, learned to give the genuine crow of a rooster. ... It was often seen scratching on the ground and calling the flock to an alleged morsel of food, and though it was never seen to tread hens it would strut and make advances after the manner of cocks. . . . The female behavior of the bird was as follows. For years it would sing like a laying hen. On two occasions it adopted incubator chicks, caring for them day and night and clucking like a normal hen. ... On one occasion it dropped an egg, which though small and elongated, showed the bird to be in possession of functional ovary and oviduct.

Its internal anatomy demonstrated the presence of a left ovotestis and a right testis. An oviduct was present on the left side and a vas deferens on both sides. The right testis contained tubules, and within the tubules were ripe sperm. The ovotestis on the left side contained a cortex studded “with oocytes of every size up to a diameter of 20 mm.” and “not unlike the ovary of a normal hen approaching the laying season” (Hartman and Hamilton, ’22) . Seminiferous tubules also were present in the ovotestis which was filled with sperm.

An interesting example of complete sex reversal was produced experimentally in the axolotl, Siredon (Ambystoma) mexicanurn, by Humphrey (’41). In doing so, Humphrey orthotopically implanted an embryonic testis of Ambystoma tigrinum into an axolotl embryo of similar age. After the ovary on the opposite side of the host (i.e., the young axolotl) had changed to a testis, the implanted testis was removed. Somewhat later, the sexually reversed female axolotl was bred with other females with success. The and F 2 generations suggest that the female axolotl is heterogametic whereas the male is homogametic, with a possible XY or ZW condition in the female and an XX (or ZZ) arrangement in the male. It is interesting to observe that Humphrey obtained YY (or WW) females which were fertile.

Many other studies have been made along the lines of experimental transformation of sex. Of these, the careful studies of Witschi (’39) are illuminating. The method, employed by Witschi, was to join two embryos of opposite sex before the period of sex differentiation. In his studies, he used toad, frog, and urodele embryos. Three different results were obtained, in which the medulla or developing testicular rudiment tended to dominate and suppress the cortex or developing female sex field. For example, in toads, it was evident that the medulla suppressed the cortex only if the two fields came into actual contact; in frogs, the effect of suppression was inversely proportional to the distance of the two sex fields from each other; on the other hand, in urodeles, the substance produced by the medulla evidently circulated in the blood stream and produced its effects at a distance (fig. 368E-G). Witschi postulated the presence of two, not readily diffusible, “activator” substances, cortexin, formed by the cortex, and medullarin, elaborated by the medulla, to account for the results in the toad and frog embryos, and, in urodeles, he assumed a hormonal substance to be present.



The foregoing examples and many others (Witschi, ’39) suggest the following interpretations relative to sex determination and differentiation:

(1) The germ cell, regardless of its genetic constitution, develops into an egg or a sperm, depending upon whether it lies in a developing cortex or in a developing medulla. That is, the influence of the sex field governs the direction of germ-cell differentiation (fig. 22).

(2) The sex field is a powerful factor in determining sex. A factor (or factors) which enables an elevation to partial or complete dominance on the part of one sex field, which under normal conditions is suppressed, may result in the partial or complete reversal of sex.

(3) Differentiation of sex is dependent upon an interplay between the genes of the sex chromosomes and the bio-chemical forces present in the gonadal sex field. This interplay may be considered to work as follows; (a) If the male-sex field or medulla in a particular species is stronger than the female field or cortex, that is, if it is able to compete for substrate substances more vigorously and successfully and to produce diffusible hormonal substance more plentifully, it will suppress the female sex field. Under these conditions, the chromosomal sex-determining mechanism is established in such a way that the male is the heterogametic sex, composed of XY or XO chromosomal combinations, and the female is XX, the genes of the extra X chromosome being necessary to override the male tendency present normally in the male sex field, (b) On the other hand, if the female sex field or cortex is stronger physiologically, then the female is the heterogametic sex (XO or ZW), the homozygous condition of the sex chromosomes in the male being necessary to suppress the natural tendencies toward supremacy of the stronger female sex field, (c) It may be that the general characteristics and strength of the sex field are controlled by genes present in certain autosomal chromosomes, whereas the specific role which the particular sex field takes normally in sex differentiation is controlled by the genes in the sex chromosomes.

2. Influence of Hormones on the Differentiation of Sex

The possible effects of hormones upon sex differentiation, particularly upon the development of the accessory ducts, have been studied with great interest since F. R. Lillie’s (T7) description of freemartin development in cattle. He tentatively made the assumption that the male fetal associate of the freemartin produces a hormonal substance which, through the medium of vascular anastomoses within the placentae of the two fetuses, brings about a partial suppression of the developing ovary and effects, in part, a sex reversal in the developing reproductive organs of the female. The female member of this heterosexual relationship, therefore, is more or less changed in the direction of the male; hence, the common name freemartin.



It should be mentioned in this connection that in the marmoset, Oedipomidas geoffroyi, similar anastomoses between the placental blood vessels of heterosexual twins fail to produce the freemartin condition, both twins being normal. Species differences in the response to hormones or other sex-modifying substances therefore occur (Wislocki, ’32).

The studies made in an endeavor to ascertain the influences which sex hormones play in the development of the reproductive system and in sexual differentiation have produced the following general results.

Developing ovaries and testes and the reproductive ducts of birds, frogs, and urodeles may show various degrees of sex reversal when the developing young are exposed to hormones or other humeral substances of the opposite sex. There is some evidence to the effect that sex reversal by sex hormones is accomplished more readily and completely from the homogametic sex to the heterogametic sex, suggesting, possibly, that the sex field of the heterogametic sex is the stronger and more resistant. The reproductive ducts are more responsive to change than are the gonads (Burns, ’38, ’39a; Domm, ’39; Mintz, Foote, and Witschi, ’45; Puckett, ’40; Willier, ’39; and Witschi, ’39).

In mammals, the gonads (ovary and testis) appear quite immune to the presence of sex hormones, whereas the reproductive ducts respond partially to the sex hormone of the opposite sex. The caudal parts of the genital passages are more sensitive to change than are the more anterior portions (Burns, ’39b, ’42; Greene, Burrill, and Ivy, ’42; and Moore, ’41, ’50).

Castration experiments before and shortly after birth in mammals produce the following effects:

(1) Removal of the testis results in retardation and suppression of the male duct system, while it allows the female duct system to develop.

(2) Removal of the ovary does not affect the female duct system until the time of puberty.

(See LaVelle, ’51, and Moore, ’50, for extensive references and discussion.)

The general conclusions to be drawn from the above experiments, relative to the differentiation of the reproductive ducts, are as follows:

(1) The reproductive ducts are responsive to sex hormones after they are formed in the embryo.

(2) The male duct system normally responds to humeral substances, elaborated by the developing testis soon after it is formed.

(3) The female duct system probably is not dependent upon hormonal secretion for its development until about the time of sexual maturity.

(4) The developing ovary, unlike the developing testis, probably under normal conditions does not elaborate sex hormones in large amounts until about the time of sexual maturity.



3. General Summary of the Factors Involved in Sex Differentiation in the Vertebrate Group

The sex glands (gonads) and the reproductive ducts appear to arise independently of each other.

The primitive gonad is composed of two main parts:

( 1 ) the primordial germ cells and

(2) cellular structures which act as supporting and enveloping structures for the germ cells.

The presence of the primitive germ cells probably is a primary requisite for the development of a functional reproductive gland (see p. 121).

In the differentiation of the gonad, two basic sex fields or territories appear to be involved in Tetrapoda and probably also in most fishes. These territories are:

( 1 ) the medulla or testis-forming territory and

(2) the cortex or ovary -forming area.

The sex fields may be controlled by the genes in the autosomal chromosomes, and there probably is a tendency for one or the other of these fields to be functionally stronger than the other. The heterogametic (XY, XO, ZW or ZO) conditions of the sex chromosomes appear to be associated with the stronger sex field, and the homogametic (i.e., XX or ZZ) combination is associated with the weaker sex field.

During development, presumably, there is a struggle for supremacy through competition for substrate substances (see Dalcq, ’49) by these two sex fields and, under normal conditions, the sex chromosomal mechanism determines which of the two sex fields shall be suppressed and which shall rise to domination. The sex chromosomes thus control the direction of sex differentiation, whereas the field or territory elaborates the power of differentiation.

Disturbing influences may upset the sex-determining mechanism set forth above, and various degrees of hermaphroditism may arise in the same individual in proportion to the degree of escape permitted the normally suppressed sex field.

The sex ducts arise in association with the pronephric kidney and its duct, the pronephric (mesonephric) duct. The Mullerian or female duct arises by a longitudinal splitting of the original pronephric (mesonephric) ducts (e.g., in elasmobranchs) or by an independent caudal growth of a small invagination of the coelomic epithelium at the anterior end of the mesonephric kidney (e.g., reptiles, birds, and mammals). This independent caudal growth is dependent, however, upon the pre-existence of the mesonephric duct (Chap. 18). In the urodeles, the Mullerian duct appears to arise partly from an independent origin and in part from contributions of the mesonephric duct.



Two sets of primitive ducts thus are established in the majority of vertebrates in each sex, the Mullerian or female duct and the mesonephric (pronephric) or male duct

During later normal development, the Mullerian duct is developed in the female, while, in the male, the mesonephric duct is retained and elaborated as the functional, male reproductive duct.

The male duct system is dependent upon secretions from the developing testis for its realization during the later embryonic period and during postnatal development, whereas the female duct develops independently of the ovary up to the time of sexual maturity when its behavior is altered greatly by the presence of the ovarian hormones.


Allen, B. M. 1929. The influence of the thyroid gland and hypophysis upon growth and development of amphibian larvae. Quart. Rev. Biol. 4:325.

. 1925. The effects of extirpation

of the thyroid and pituitary glands upon the limb development of anurans. J. Exper. Zool. 42:13.

Brahms, S. 1932. The development of the hypophysis in the cat (Felis domestica). Am. J. Anat. 50:251.

Bridges, C. B. 1939. Chap. II, Cytological and genetic basis of sex. Sex and Internal Secretions, 2nd Edition. Edited by Allen, et al., Williams & Wilkins, Baltimore.

Burns, R. K., Jr. 1938. The effects of crystalline sex hormones on sex differentiation in Amhly stoma, I. Estrone. Anat. Rec. 71:447.

. 1939a. The effects of crystalline

sex hormones on sex differentiation in Amblystoma. II. Testosterone propionate. Anat. Rec. 73:73.

. 1939b. Sex differentiation during

the early pouch stages of the opossum (Didelphys virginiana) and a comparison of the anatomical changes induced by male and female sex hormones. J. Morphol. 65:497.

. 1942. Hormones and experimental

modification of sex in the opossum. Biol. Symp. 9: 125.

Chen, G., Oldham, F. K., and Geiling, E. M. K. 1940. Appearance of the melanophore-expanding hormone of the pituitary gland in the developing chick embryo. Proc. Soc. Exper. Biol. & Med. 45:810.

Cooper, E. R. A. 1925. The histology of the more important human endocrine organs at various ages. Oxford University Press, Inc., New York.

Dalcq, A. M. 1949. The concept of physiological competition (Spiegelman) and the interpretation of vertebrate morphogenesis. Exp. Cell Research, Supplement 1, Bonnier, Stockholm and Academic Press, New York.

Domm, L. V. 1939. Chap. V. Modifications in sex and secondary sexual characters in birds in Sex and Internal Secretions by Allen, et al., 2d ed.. The Williams & Wilkins Co., Baltimore.

Greene, R. R., Burrill, M. W., and Ivy, A. C. 1942. Experimental intersexuality. The relative sensitivity of male and female rat embryos to administered estrogens and androgens. Physiol. Zodl. 15:1.

Gudernatsch, J. F. 1912. Feeding experiments on tadpoles. I. The influence of specific organs given as food on growth and differentiation. A contribution to the knowledge of organs with internal secretion. Arch. f. Entwicklngsmech. d. Organ. 35:457.

, 1914. Feeding experiments on tadpoles. II. A further contribution to the knowledge of organs with internal secretion. Am. Jour. Anat. 15:431.

Hall, A. R., and Kaan, H. W. 1942. Anatomical and physiological studies on the thyroid gland of the albino rat. Anat. Rec. 84:221.



Hartman, C. G., and Hamilton, W. F. 1922. A case of true hermaphroditism in the fowl, with remarks upon secondary sex characters. J. Exper. ZooL 36:185.

Hopkins, M. L. 1935. Development of the thyroid gland in the chick embryo. J. Morphol. 58:585.

Hoskins, E. R. and M. M. 1918. Further experiments with thyroidectomy in Amphibia. Proc. Soc. Exper. Biol. & Med. 15:102.

. 1919. Growth and development of

Amphibia as affected by thyroidectomy. J. Exper. Zool. 29:1.

Howard, E. 1939. Effects of castration on the seminal vesicles as influenced by age, considered in relation to the degree of development of the adrenal X zone. Am. J. Anat. 65:105.

LaVelle, F. W. 1951. A study of hormonal factors in the early sex development of the golden hamster. Contrib. to Embryol. Carnegie Inst., Washington, Publ. 34:223.

Lillie, F. R. 1917. The free-martin; a study of the action of sex hormones in the fetal life of cattle. J. Exper. Zool. 23:371.

Lynn, W. G., and Wachowski, H. E. 1951. The thyroid gland and its functions in cold-blooded vertebrates. Quart. Rev. Biol. 26:123.

Mintz, B., Foote, C. L,, and Witschi, E. 1945. Quantitative studies on response of sex characters of differentiated Rana clamitans larvae to injected androgens and estrogens. Endocrinology. 37:286.

Moore, C. R. 1941. On the role of sex hormones in sex differentiation in the opossum {Didelphys virginiana). Physiol. Zool. 14:1.

. 1950. The role of the fetal endocrine glands in development. J. Clin. Endocrinol. 10:942.

Puckett, W. O. 1940. Some effects of crystalline sex hormones on the differentiation of the gonads of an undifferentiated race of Rana catesbiana tadpoles. J. Exper. Zool. 84:39.

Rahn, H. 1939. The development of the chick pituitary with special reference to the cellular differentiation of the pars buccalis. J. Morph. 64:483.

Rankin, R. M. 1941. Changes in the content of iodine compounds and in the histological structure of the thyroid gland of the pig during fetal life .Anat. Rec. 80:123.

Rumph, P., and Smith, P. E. 1926. The first occurrence of secretory products and of a specific structural differentiation in the thyroid and anterior pituitary during the development of the pig foetus. Anat. Rec. 33:289.

Selye, H. 1948. Textbook of Endocrinology. Universite de Montreal, Montreal, Canada.

Smith, P. E. 1916. The effect of hypophysectomy in the early embryo upon growth and development of the frog. Anat. Rec. 11:57.

. 1920. The pigmentary growth and

endocrine disturbances induced in the anuran tadpole by the early ablation of the pars buccalis of the hypophysis. Am. Anat. Memoirs. 11, The Wistar Institute of Anatomy and Biology, Philadelphia.

Wheeler, R. S., and Hoffman, E. 1948a. Goitrous chicks from thyroprotein-fed hens. Endocrinology. 42:326.

and . 1948b. Influence of

quantitative thyroprotein treatment of hens on length of incubation period and thyroid size of chicks. Endocrinology. 43:430.

White, M. J. D. 1948. Animal Cytology and Evolution, Chap. XI. Cambridge University Press, London.

Willier, B. E. 1921. Structures and homologies of free-martin gonads. J. Exper. Zool. 33:63.

. 1939. Chap. III. The embryonic

development of sex in Sex and Internal Secretions by Allen, et al., 2d ed.. The Williams & Wilkins Co., Baltimore.

Wislocki, G. B. 1932. Placentation in the marmoset {Oedipomidas geoffroyi) with remarks on twinning in monkeys. Anat. Rec. 52:381.

Witschi, E. 1939. Chap. IV. Modification of the development of sex in lower vertebrates and in mammals in Sex and Internal Secretions by Allen, et al., 2d ed., The Williams & Wilkins Co., Baltimore.