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العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt These external translations are automated and may not be accurate. (More? About Translations) |
Nelsen OE. Comparative embryology of the vertebrates (1953) Mcgraw-Hill Book Company, New York.
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Part IV - Histogenesis and Morphogenesis of the Organ Systems
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
The 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
The 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
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
The 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
The 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
The 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
The 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
The 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
805
806
THE NERVOUS SYSTEM
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
INTRODUCTION
807
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
808
THE NERVOUS SYSTEM
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.)
BASIC DEVELOPMENTAL FEATURES
809
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).
810
THE NERVOUS SYSTEM
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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Fig. 353. (See facing page for legend.)
811
812
THE NERVOUS SYSTEM
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.
BASIC DEVFXOP MENTAL FEATURES
813
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
814
THE NERVOUS SYSTEM
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
BASIC DEVELOPMENTAL FEATURES
815
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
816
THE NERVOUS SYSTEM
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
BASIC DEVELOPMENTAL FEATURES
817
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.
MUSCLE LAVERS OF
INTESTINAL WALLS
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
aiQ
MORPHOGENESIS OF CENTRAL NERVOUS SYSTEM
819
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.
820
THE NERVOUS SYSTEM
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
MORPHOGENESIS OF CENTRAL NERVOUS SYSTEM
821
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
822
THE NERVOUS SYSTEM
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
DEVELOPMENT OF PERIPHERAL NERVOUS SYSTEM
823
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
myelencephalon
PREMUSCLE MASS OF sternomastoid
AND â–
MUSCLES OF SHOULDFR ARE
I LATERAL HALE OF retina
ABBREVIATIONS'
G>SO A EX --GENERAL SOMATIC AFFERENT FIBERS.
(EXTEROCEPTIVE FIBERSj G.SO.A.P,' GENERAL SOMATIC AFFERENT FIBERS.
(PROPRIOCEPTIVE FIBERS)
GV A » GENERAL VISCERAL AFFERENT FIBERS SP V A." SPECIAL VISCERAL AFFERENT FIBERS SP SO. A -- SPECIAL SOMATIC AFFERENT F I0E RS ( EX, AND P. ^ v V CUTANEOUS BRANCHES
OF THE
COMMUNIS ROOT OF THE
RIGHT FACIAL NERVE
COMMISSURE CONNECTING LINES OF TWO SIDES SUPRAORBITAL LINE OF ORGANS N. SUPERFICIALIS OPHTHALMICUS OLFACTORY LOBE ' NARES
BUCCALIS RAMUS
LATERAL LINE CANAL
'ENTRAL RAMUS /OF LATERALIS / OF N.X VISCERALIS PART OF N.X â– OPERCULUM HYOMANOIBULARIS
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
824
DEVELOPMENT OF PERIPHERAL NERVOUS SYSTEM
825
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.)
826
THE NERVOUS SYSTEM
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
DEVELOPMENT OF PERIPHERAL NERVOUS SYSTEM
827
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
828
THE NERVOUS SYSTEM
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.
DEVELOPMENT OF PERIPHERAL NERVOUS SYSTEM
829
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
830
THE NERVOUS SYSTEM
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
DEVELOPMENT OF PERIPHERAL NERVOUS SYSTEM
831
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
HINDBRAIN
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
832
DEVELOPMENT OF PERIPHERAL NERVOUS SYSTEM
833
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.)
834
THE NERVOUS SYSTEM
JSJT) GANGLIA
sensory
i jTT-n LATERAL LINE
VISCERAL MOTOR (00"» SOMATIC MOTOR
posttrematic Rami of the
GLOSSOPHARYNGEAL AND VAGUS NERVES
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
DEVELOPMENT OF PERIPHERAL NERVOUS SYSTEM
835
1 OLFACTORY
OLFACTORY LOBE
CEREBRAL HEMISPHERES
RANSVERSE FISSURE •CEREBELLUM
MEDULLA OBLONGATA
SPINAL CORD 0.
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
836
THE NERVOUS SYSTEM
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.â€
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
Nerves
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
DEVELOPMENT OF PERIPHERAL NERVOUS SYSTEM
837
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.
838
THE NERVOUS SYSTEM
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
840
SENSE OR RECEPTOR ORGANS
841
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).
842
THE NERVOUS SYSTEM
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
The Development of the 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
857
858
THE DEVELOPMENT OF THE COELOMIC CAVITIES
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
EARLY DIVISION OF SPLANCHNOCOELIC COELOM
859
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
NEURAL TUBE
NOTOCHORD
DORSAL PARIETAL RECESS OF HIS
PLEURO ERICAROIAL CANAL
NEURAL TUBE
DORSAL aorta DORSAL CLOSING FOLD CONTRIBUTION FROM SPLANCHNOPLEURIC
MESODERM DUCT OF CUVIER lORSAL CLOSING FOL CONTRIBUTION FROM SOMATOPLEURIC MESODERM LATERAL MESOCARDIUM SINUS VENOSUS heart (ATRIUM) LIVER
c DORSAL
MESOG^TRIUM
VENTRAL MESENTERY GASTROHEPATIC LIGAMENT 'LESSER OMENTUM)
dorsal pancreas
DORSAL MESENTERY
DORSAL aorta NEURAL TUBE
ventral
MESENTERY
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
860
EARLY DIVISION OF SPLANCHNOCOELIC COELOM
861
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.
FOREBRAIN
STERNAL RIB
Fig. 362 — (Continued)
See legend on p. 860 .
EARLY DIVISION OF SPLANCHNOCOELIC COELOM
863
(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
PLEUROPERITONEAL
PLEUROPERITONEAL ' RUDIMENT OF DIAPHRAGM
PLEURAL CAVIT
hepato duodenal
LIGAMEm
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).
864
EARLY DIVISION OF SPLANCHNOCOELIC COELOM
865
CARDINAL VEIN
COMMON CARDINAL VEIN AND LATERAL ' MESOCARDIUM IN ANTERIOR LATERAL BODY FOLD
SINUS ^ VENOSUS SEPTUM TRANSVERSUM CUT EDGE OF LIVER
LEUROPERICARDIAL CANAL BELOW ESOPHAGUS
PULMONARY RIDGE GROWING MESAO BELOW LUNG BUD AS PLEURO PERICARDIAL MEMBRANE
ANTERIOR CARDINAL VEIN PERICARDIAL CAVITY ■PULMONARY ridge. COMMON CARDINAL VEI COUCT OF CUVIER! PLEURAL CAVITY POSTERIOR LATERAL BODY FOLD • lateral RUDIMENT OF PLEUROPFRITONEAL MEMBRANE
SPI.ANCHNOPLEURIC CONTRIBUTION LIVER STOMACH
PLEUROPERICARDIAL MEMBRANE COMPLETE BELOW LUNG
- pleural CAVIT
POSTERIOR LATERAL BODY FOLD AND SPLANCHNOPLEURIC CONTRIBUTION FUSE TO FORM PLEUROPERITONEAL MEMBRANE
CUT DORSAL EDGE OF PLEUROPERITONEAL MEMBRANE STOMACH PERITONEAL cavity DORSAL mesentery
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
866
THE DEVELOPMENT OF THE COELOMIC CAVITIES
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
COELOMIC CHANGES IN FISHES, AMPHIBIANS, REPTILES, AND BIRDS
867
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,
868
THE DEVELOPMENT OF THE COELOMIC CAVITIES
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
FORMATION OF COELOMIC CAVITIES IN MAMMALS
869
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
870
MAMMALIAN DIAPHRAGM
871
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.
872
THE DEVELOPMENT OF THE COELOMIC CAVITIES
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
PULMONARY DIAPHRAGM OF CHICK
873
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.)
Bibliography
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.
21
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
874
INTRODUCTION
875
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.â€
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
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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).
ORIGIN OF THE ENDOCRINE GLANDS
877
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.
878
THE DEVELOPING ENDOCRINE GLANDS
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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.
ORIGIN OF THE ENDOCRINE GLANDS
879
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
880
THE DEVELOPING ENDOCRINE GLANDS
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 sweetbreadâ€) 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
ORIGIN OF THE ENDOCRINE GLANDS
881
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.â€
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.
882
THE DEVELOPING ENDOCRINE GLANDS
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.â€
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
DEVELOPMENT OF DEFINITIVE BODY FORM
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1 ^* ' ^ '
-MESONEPHRIC TUBULE
-aortic wall
y0'
%
CHROMAFFIN TISSUE FORMING MEDULLA
OF adrenal gland A-:
k
aorta
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.,
884
THE DEVELOPING ENDOCRINE GLANDS
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
DEVELOPMENT OF DEFINITIVE BODY FORM
885
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
886
THE DEVELOPING ENDOCRINE GLANDS
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
CORRELATION OF ENDOCRINE GLANDS WITH SEX DIFFERENTIATION
887
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
888
THE DEVELOPING ENDOCRINE GLANDS
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.)
CORRELATION OF ENDOCRINE GLANDS WITH SEX DIFFERENTIATION
889
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
890
THE DEVELOPING ENDOCRINE GLANDS
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.
CORRELATION OF ENDOCRINE GLANDS WITH SEX DIFFERENTIATION
891
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.
892
THE DEVELOPING ENDOCRINE GLANDS
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.
CORRELATION OF ENDOCRINE GLANDS WITH SEX DIFFERENTIATION
893
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.
894
THE DEVELOPING ENDOCRINE GLANDS
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.
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