ANA 222 2023 2024 lecture notes.docx

**EMBRYOLOGY** **DEVELOPMENT OF MUSCULAR SYSTEM** The formation of the muscular system begins about 4th week of embryonic development. The beginning cells are called Myoblasts. Most of our muscles develops from the mesodermal germ layer. Except some smooth muscle tissues (pupil, sweat glands and...

**EMBRYOLOGY** **DEVELOPMENT OF MUSCULAR SYSTEM** The formation of the muscular system begins about 4th week of embryonic development. The beginning cells are called Myoblasts. Most of our muscles develops from the mesodermal germ layer. Except some smooth muscle tissues (pupil, sweat glands and mammary gland differentiate from ectoderm). The muscular system consist of; 1\. Skeletal musculature 2\. Cardiac musculature 3\. Smooth musculature **General Overview** **The musculoskeletal system** develops from three types of cell populations: the paraxial mesoderm, lateral plate mesoderm, and neural crest.  The development of bone and muscle begins at the fourth gestational week, when the paraxial mesoderm differentiates into  somites; the latter gives rise to sclerotomes and dermomyotomes.  Sclerotomes  form the vertebra and the ribs, whereas  [[myotomes]](https://www.kenhub.com/en/library/anatomy/myotomes)  form the majority of the muscular system. Bone formation can occur either by intramembranous ossification or  [[endochondral ossification]](https://www.kenhub.com/en/library/anatomy/endochondral-ossification). Although different, the occurrence of both processes first require the condensation of  [[mesenchymal cells]](https://www.kenhub.com/en/library/anatomy/mesecnhymal-cells) - the loosely organized embryonic  [[connective tissue]](https://www.kenhub.com/en/library/anatomy/overview-and-types-of-connective-tissue).  Intramembranous ossification  underlies the formation of the cranial vault, many bones of the face, and the clavicle.  Endochondral ossification  underlies the formation of the base of the  [[skull]](https://www.kenhub.com/en/library/anatomy/the-skull) , some bones of the face, the bones of the limbs and girdles, the  [[vertebral column]](https://www.kenhub.com/en/library/anatomy/the-vertebral-column-spine), the ribs, and the  [[sternum]](https://www.kenhub.com/en/library/anatomy/sternum). Development of the limbs involves the inductive influences of the  apical ectodermal ridge, the formation of circular constrictions to separate parts of the limbs, and opposite rotations of the upper and lower limbs. Development of the skeletal muscle involves the differentiation of myotome cells into  myoblasts. This article will discuss the embryological development of the axial skeleton, the appendicular skeleton, and the skeletal muscle, as well as the associated malformations that may occur. **MESODERMAL DEVELOPMENT** **The Paraxial mesoderm**, is the area of mesoderm in the neurulating embryo that flanks and forms simultaneously with the neural tube. The cells of this region give rise to somites, blocks of tissue running along both sides of the neural tube, which form muscle and the tissues of the back, including connective tissue and the dermis. Paraxial mesoderm development is composed of several stages: presomitic mesoderm specification, somitogenesis, and somite specification1. Mature somites contain two major populations: the **sclerotome and dermomyotome**. The sclerotome gives rise to the vertebrae and associated ribs, tendons, and other tissues, such as vascular cells of the dorsal aorta, intervertebral blood vessels, and meninges. The dermomyotome produces two components: the **myotome and the dermatome**. The myotome gives rise to the musculature of the back, rib cage, ventral body wall, and limbs. The dermatome gives rise to the dermis of the back, although the term dermomyotome is sometimes used to describe this region because a recent study showed that this central region of the dermomyotome also gave rise to muscles in chick embryos. The lateral plate mesoderm forms the splanchnic mesoderm, somatic mesoderm, and extraembryonic membranes, as evidenced by a study of chick embryos^.^. The splanchnic mesoderm gives rise to components of the circulatory system, such as the heart, blood vessels, and blood cells, whereas the somatic mesoderm forms the pelvic skeleton and mesodermal components of the limbs, with the exception of the muscles, which are derived from the dermomyotome. The intermediate mesoderm forms the urogenital system, including the kidneys and gonads. **Specification of the presomitic mesoderm** The early paraxial mesoderm is referred to as the presomitic mesoderm, and consists of bilateral streaks of mesenchymal cells adjacent to the notochord, The presomitic mesoderm is derived from the primitive streak or neuromesodermal progenitors in the tail bud, as shown in studies with mouse and bird embryos^,^. In these steps, Noggin produced by the notochord protects the paraxial mesoderm from lateralization by BMPs produced by the intermediate mesoderm and lateral plate mesoderm. This gradient is crucial for mesodermal cell fate determination. When Noggin-expressing cells were implanted into the presumptive lateral plate region, somitic tissues were formed in the original lateral plate territory of chick embryos. This demonstrates that the paraxial mesoderm and lateral plate mesoderm share common precursors in the primitive streak, and that the cell fate is plastic, depending on the gradients of BMP activity. **Fig. 1: Overview of the mesodermal derivatives.** figure 1**The chordamesoderm and paraxial mesoderm form the axial skeleton, whereas the intermediate mesoderm forms the kidneys and gonads, and the lateral plate mesoderm forms the circulating systems, body wall, and limbs (except for the musculature). nt neural tube.** **Fig. 2: Schematic of the relationship between the sclerotome and other tissues.**  **A large part of the sclerotome is induced depending on Shh signaling from the notochord and floor plate. Shh also competes with Wnt, which induces the dermomyotome and maintains the epithelial state in somites. The notochord also produces Noggin, which inhibits BMP signaling and supports sclerotome induction[](https://www.nature.com/articles/s12276-020-0482-1#ref-CR63). nt neural tube, n notochord, ao dorsal aorta, DM dermomyotome, M myotome, IM intermediate mesoderm, LPM lateral plate mesoderm.** Derived tissues --------------- Many kinds of tissue derive from the segmented paraxial mesoderm by means of the somite. Among these are: - - - - ### ### Appendicular skeleton While the external shape of the limbs becomes established, the bones of the limbs and girdles (with the exception of the clavicle) form by a two-step process: chondrification and endochondral ossification. In contrast, the clavicle is a membrane bone: it forms directly by intramembranous ossification. Chondrification involves the condensation and differentiation of mesenchymal cells into chondrocytes (cartilage cells). By the sixth gestational week, these chondrocytes differentiate into hyaline cartilage models, foreshadowing the prospective bones. While the process of forming these cartilage models is initiated, synovial joints form between the two chondrifying bone primordia at the interzone. At birth, the diaphysis of long bones is usually completely ossified, whereas the epiphyses are still cartilaginous. Only after birth, secondary ossification centers develop in the epiphyses, which will also undergo the same ossification and vascularization processes that took place in the diaphysis. However, a layer of epiphyseal cartilage plate, known as the growth plate, persists between the epiphyses and the diaphysis. Continued proliferation of the chondrocytes in the growth plate is what allows the diaphysis to lengthen and thus what maintains the growth of bones. Only at approximately 20 years of age are when the epiphyses and diaphysis fuse, indicating that skeletal growth is complete. **SKELETAL MUSCLE** Skeletal muscle develops from paraxial mesoderm which forms; a. Somites from the occipital to the sacral regions b. Somitomeres in the head Skeletal muscle is derived from paraxial mesoderm which forms segmented series of tissue blocks on each side of the neural tube, the somites. Cells in the ventromedial part of the somite form the sclerotome. Cells in the dorsal part form the [[dermatome]](https://www.kenhub.com/en/library/anatomy/dermatomes) and two edges, the ventrolateral lip and the dorsomedial lip. Cells from these two edges migrate ventral to the dermatome and proliferate to form muscle cell precursors. Collectively, these structures form the dermomyotome. In turn, the dermomyotome will differentiate into dermatome cells forming the [[dermis]](https://www.kenhub.com/en/library/anatomy/dermis) of the back and the neck, and myotome cells forming the skeletal muscles. Before developing into skeletal muscles, myotome cells first differentiate into myoblasts (embryonic muscle cells) through elongation of their nuclei and cell bodies. Myoblasts fuse to form elongated, multinucleated, and cylindrical muscle fibers. During or after fusion, [[myofilaments]](https://www.kenhub.com/en/library/anatomy/myofilament) and [[myofibrils]](https://www.kenhub.com/en/library/anatomy/myofibrils) develop in the cytoplasm. As development continues, the muscle cells become invested with the external laminae, segregating them from the surrounding connective tissue. [Fibroblasts](https://www.kenhub.com/en/library/anatomy/fibroblast) form the [epimysium](https://www.kenhub.com/en/library/anatomy/epimysium) and [perimysium](https://www.kenhub.com/en/library/anatomy/perimysium) layers of the muscle, whereas the external lamina and [reticular fibers](https://www.kenhub.com/en/library/anatomy/reticular-fibers) form the endomysium. In limbs, myoblasts migrate to the limb buds and surround the primordial limb bones. The pattern of muscle formation is dictated by the same mesenchymal cells that give rise to the bones. Myofibrils soon appear in the cytoplasm, and by the end of the third month, cross- striations appear in skeletal muscle A similar process occurs in the seven somitomeres in the head region rostral to the occipital somites. **Patterning of muscle** Patterns of muscle formation are controlled by connective tissue into which myoblasts migrate In the head region these connective tissues are derived from neural crest cells; in cervical and occipital regions they differentiate from somatic mesoderm; and In the body wall and limbs they originate from somatic mesoderm. **Derivatives of precursors muscle cells** By the end of the 5th week prospective muscle cells are collected into two parts: Epimere (small dorsal portion) -- innervated by the dorsal primary ramus Hypomere (larger ventral part) -- innervated by the ventral primary ramus Myoblasts of the epimeres form the extensor muscles of the vertebral column, and those of the hypomeres give rise to muscles of the limbs and body wall. a. Those from thoracic segments split into three layers, which in the thorax are represented by; External Intercostal Internal Intercostal Innermost Intercostal. b. In the abdominal wall these three muscle layers consist of the external oblique, the internal oblique, and the transversus abdominis muscles. c. Myoblasts from the hypoblast of lumbar segments form the quadrates lumborum muscle d. Those from sacral and coccygeal regions form the pelvic diaphragm and striated muscles of the anus. e. A ventral longitudinal column arises at the ventral tip of the hypomeres. This column is represented by the rectus abdominis muscle and the infrahyoid musculature Smooth muscles differentiate from splanchnic mesoderm surrounding the gut and its derivatives. Cardiac muscles are derived from splanchnic mesoderm surrounding the heart tube **HEAD MUSCULATURE** All voluntary muscles of the head region are derived from paraxial mesoderm (somitomeres and somites); Including muscle of the tongue, eye (except that of the iris, which is derived from optic cup ectoderm), and that associated with the pharyngeal (visceral) arches. Patterns of muscle formation in the head are directed by connective tissue elements (Neural crest cells). **Limb musculature** Connective tissue dictates the pattern of muscle formation in the limb Derived from the somatic mesoderm The mesenchyme is derived from dorsolateral cells of the somites that migrate into the limb bud to form the muscles. With elongation of the limb buds, the muscle tissue splits into flexor and extensor components. The upper limb buds lie opposite the lower five cervical and upper two thoracic segments, and the lower limb buds lie opposite the lower four lumbar and upper two sacral segments. **THE INTEGUMENTARY SYSTEM** The integumentary system is the largest organ system in the human body, responsible for protection from physical and environmental factors. The integumentary system is both a barrier and a sensory organ, and includes the skin (the largest bodily organ), as well as appendages, sweat and sebaceous glands, hair, nails and arrectores pillorum (tiny muscles at the root of each hair that cause goose bumps). Integumentary system develops from surface ectoderm and the underlying mesenchyme **Fetal Skin Formation** A. **Epidermis:** initially the embryo\'s surface is covered by a single layer of ectodermal cells which, in the second month divides to form a superficial protective layer of simple, flattened squamous epithelial cells, the *periderm or epitrichium* a. i. b. ii. c. iii. iv. v. vi. d. e. vii. 1. f. viii. g. 2. 3. If the superficial layers of the skin show excessive cornification, the skin has a scaly appearance, a condition spoken of as *icthyosis* This diagram of the integumentary system indicates the hair shaft, sweat pore, dermal papilla, sensory nerve ending for touch, epidermis, dermis, subcutis (hypodermic), vein, artery, sweat gland, pacinian corpuscle, blood and lymph vessels, nerve fiber, papilla of hair, hair follicle, sebaceous gland, arrector pili muscle, stratum basale, stratum spinosum, stratum germinativum, pigment layer, and stratum corneum. ***Human Skin**: This image details the parts of the integumentary system.* **Overview of skin embryology** a. b. c. d. e. f. g. h. ***DEVELOPMENT OF THE HAIR*** I. The hair appears as a solid epidermal down growth of the stratum germinativum into the underlying dermis and is called the *hair bud* B. THE DEEPEST PORTION OF THE HAIR BUD becomes club-shaped and forms the *hair bulb* 4. The epithelial cells of the hair bulb constitute the *germinal matrix*, which later will give rise to the hair 5. The hair bulb is then invaginated by a small mesenchymal *hair papillae* 6. As the cells of the germinal matrix, in the center of the hair follicles, proliferate, they are pushed upward and become keratinized forming the *hair shaft*. The peripheral cells of the developing hair follicle form the *epithelial root (hair) sheath* h. The surrounding mesenchymal cells differentiate into the *dermal (connective tissue) root sheath* 7. The hair grows, penetrates the epidermis, and appears above the skin surface 8. Melanoblasts invade the hair bulb and form melanocytes. They produce melanin which is transferred to the hair-forming cells in the germinal matrix before birth C. HAIRS BEGIN TO DEVELOP during early fetal life, but become visible at about week 20 on the eyebrows, upper chin, and lips and are called the *lanugo hairs* 9. The lanugo are shed at about the time of birth and are later replaced by coarser hairs called *vellus hairs* which arise from new hair follicles i. The vellus persists over most of the body except in the axillary and pubic regions where, at puberty, they are replaced by coarse *terminal hairs* (seen also on the chest and face in males) D. THE ARRECTOR PILI MUSCLES are smooth muscle fibers which form from the surrounding mesenchyme and become attached to the connective tissue sheath of the hair follicle and dermal papillary layer II. The sebaceous glands develop as buds from the side of the developing epithelial root sheath of the hair follicle E. THE BUDS GROW into the surrounding connective tissue and branch to form the primordia of the glandular alveoli and ducts 10. The central cells of the alveoli break down and form an oily secretion, the *sebum*, which is extruded into the hair follicle and onto the skin surface to mix with the desquamated peridermal cells to help form the vernix caseosa F. INDEPENDENT GLANDS (not with hair follicles) also develop from the epidermis in the areas of the glans penis and the labia minora III. Sweat (eccrine or merocrine) glands develop as a solid epidermal bud which grows down into the underlying dermis G. AS THE BUD ELONGATES, its end coils to form the primordium of the glands secretory portion, while the epithelial attachment to the epidermis forms the duct primordium 11. The central cells of the primordia degenerate to form a lumen 12. The peripheral cells of the secretory portion of the gland differentiate into *secretory* and *myoepithelial cells*, the latter being specialized ectodermal smooth muscle cells which aid in expelling the glandular secretion IV. Sweat (apocrine) glands in humans, are confined to the axilla, pubic areas, and areola of the mammary glands H. THEY DEVELOP as downgrowths of the stratum germinativum of the epidermis 13. Their ducts open into the hair follicles and not on the skin surfac They open just above the sebaceous glands 14. Their chief function seems to be the production of small amounts of secretions which, on the surface, give rise to distinctive odors that enable animals to recognize each other. Human apocrine sweat glands have no odor in their secretion but contain substances readily degraded by bacteria into odiferous breakdown products 15. **\ DEVELOPMENT OF THE NAILS** V. Nails are modifications of the epidermis and correspond to the claws and hoofs of lower animals I. THE FIRST INDICATION of a nail is foreshadowed at week 10 by a thickened area of epidermis, the *nail field*, seen on the dorsum of each digit 16. The adjoining area, on each side and at the base of the field, tends to overgrow the field, giving rise to shallow *lateral nailfolds* which continue into a much deeper *proximal nailfold* that extends nearly to the proximal end of the terminal phalanx 17. Development at the tips of the fingers precedes the development of the toenails J. THE MATERIAL of the true nail is developed within the underlayer of the proximal nailfold (although the primitive nail field undergoes some local cornification and forms a so-called false nail). This layer is named the *matrix* 18. During month 5, specialized keratin fibrils differentiate in the matrix layer, without having passed through a keratohyalin or eleidin stage (ordinary method of cornification) 19. The keratinized cells flatten and consolidate into the compact tissue of which the *nail plate* is composed 20. Thus, the nail substance differentiates in the proximal nailfold as far distal as the outer edge of the lunula (the whitish crescent at the base of the exposed nail) 21. Beyond the lunula, the nail plate merely shifts progressively over the *nail bed* and reaches the tip of the finger about 1 month before birth 22. The dermis, beneath the nail, is thrown into parallel longitudinal folds to produce the characteristic ridges and grooves K. THE STRATUM CORNEUM AND PERIDERM of the epidermis, for a time, cover completely the free nail and are jointly referred to as the *eponychium* 23. This layer, in late fetuses, is lost except for horny portions that continue to adhere to the nail plate along the curved rim of the nailfold (the *cuticle*) L. UNDERNEATH THE FREE END of the nail, the epidermal cells also accumulate to form a piled-up epidermal mass, the *hyponychium*, or substance beneath the nail VI. **Nail anatomy** M. THE HORNY ZONE of the nail is composed of hard keratin and has a distal, exposed part or *body*, and a proximal, hidden portion, the *root* 24. The root is covered by a prolongation of the stratum corneum of the skin which is composed of soft keratin and is called the eponychium 25. The lunula or \"half-moon\" lies distal to the eponychium and is a part of the horny zone which is opaque to the underlying capillaries 26. The horny zone of the nail is attached to the underlying nail bed 27. The matrix, or proximal part of the nail bed, produces hard keratin 28. The fingernails reach the fingertips by week 32, and the toenails reach the toe tops by week 36 29. On the average, after birth, the nail grows about 0.5 mm a week. They grow faster in the summer than in the winter; growth is also age dependent N. **Malformations of the hair and nails** O. CONGENITAL ALOPECIA (atrichia congenita): fetal loss or absence of hair may occur by itself or with other skin derivative abnormalities P. HYPERTRICHOSIS: excessive hairiness due to the development of supernumerary follicles or persistence of fetal hair that normally disappears Q. ANONYCHIA: partial or complete absence of the nails due to a failure of the matrix to form or give origin to the nails R. MISSHAPEN NAILS are a common occurrence **DEVELOPMENT OF THE MAMMARY GLAND** I. The mammary glands (breasts) are derived from 2 thickened strips of epidermal ectoderm, the *primitive mammary ridges or milk lines*, which appear during week 6. The ridges extend from the axillae to the inguinal regions, but rapidly regress except in the thorax A. THE MAMMARY BUDS that persist in the thoracic region penetrate the underlying mesenchyme and give rise to several secondary buds which develop into *lactiferous ducts* and their branches. These are canalized by the end of the prenatal life 1. The fibrous connective tissue and fat of the mammary gland develop from the surrounding mesenchym The lactiferous ducts form the small ducts and alveoli 2. Only the main ducts are found at birth, and the gland remains undeveloped until puberty B. DURING THE LATE FETAL PERIOD, the epidermis, where the gland originated, becomes depressed to form a shallow *mammary pit* (epithelial pit) on which the ducts open 3. The lactiferous ducts at first open onto this epithelial pit which is formed by the original mammary line C. THE NIPPLE itself forms during the perinatal period due to proliferation of the mesenchyme under the areola (circular area of skin around the nipple) in the area of the mammary pit. The nipple is often depressed and poorly formed during infancy D. THE MAMMARY GLANDS of both newborn males and females are often enlarged and may secrete \"witches\' milk\" or *colostrum*, as a result of maternal hormones passing into the fetal circulation by way of the placenta E. AT PUBERTY, the female mammary glands enlarge rapidly as a result of the development of fat and connective tissue. The duct system also grows, stimulated by the estrogen and progesterone of the ovary 4. The glandular tissue remains completely undeveloped until pregnancy when the intralobular ducts rapidly develop, form buds, and become alveoli 5. The male glands undergo little postnatal development II. Malformations of the mammary gland F. ABSENCE OF THE GLAND (AMASTIA) AND/OR NIPPLE (ATHELIA) is rare; may occur bilaterally or unilaterally, and is due to failure of development or complete disappearance of the mammary ridge(s). Also can be due to failure of the mammary bud to form. G. SUPERNUMERARY BREASTS (POLYMASTIA) AND NIPPLES (POLYTHELIA) are seen in about 1% of the female population and are usually inherited. They generally are found below the normal breast, but less commonly are seen in the axilla or abdominal area, developing along the mammary ridges 6. Polythelia is uncommon, also may be seen in males 7. In most cases, a single extra nipple or breast is seen, but in 30% of cases, 2 extra nipples or breasts are found 8. Accessory breasts may have normal tissue and even function during lactation H. INVERTED NIPPLES: the nipple fails to develop normally and evert after birth. Probably due to a failure of the underlying mesenchyme to proliferate and push the nipple out 9. Also may be caused by retraction of the nipple as a result of the presence of a fast-growing tumor in the gland **DEVELOPMENT OF THE TEETH** I. Introduction: the teeth develop from ectoderm and mesoderm: the enamel develops from ectoderm of the oral cavity, and all other tissues come from the associated mesenchyme. Not all teeth develop at the same time. The first tooth buds are seen in the anterior mandibular region, later in the anterior maxillary region, then posteriorly in both jaws. Development is in continuous stages A. THE DENTAL LAMINA AND BUD STAGE: the dental laminae are seen early in week 6 as U-shaped thickenings or buds of the oral epithelium (surface ectoderm) 1. Localized proliferation of cells in the dental laminae forms round or oval swellings, the *tooth buds*, which grow into the mesenchyme 2. The tooth buds develop into the *deciduous or milk teeth* (shed during childhood). There are 10 tooth buds in each jaw, one for each tooth 3. The tooth buds for the permanent teeth, with deciduous predecessors, are seen in the 10-week fetus, developing from deeper continuations of the dental lamin They lie on the tongue or lingual side of the deciduous buds 4. Tooth buds for the permanent teeth appear at different ages during the fetal period except for the second and third permanent molars, which appear after birth, at about 4 months and 5 years, respectively 5. The permanent molars with no deciduous predecessors develop as buds from backward extensions of the dental laminae B. CAP STAGE OF DEVELOPMENT: the deep surface of each ectodermal tooth bud becomes invaginated by mesenchyme called the *dental papilla*, which gives rise to the *dentin* and *dental pulp*. The ectodermal, cap-shaped covering over the papilla is called an *enamel organ* since it will produce the future enamel of the tooth 6. The outer cellular layer of the ectodermal enamel organ is called the *outer enamel epithelium*; the inner layer lining the \"cap\" is the *inner enamel epithelium* a. The cell region between the above layers forms the core or bulk of the cap and is called the *stellate or enamel reticulum* 7. As the enamel organ and dental papilla form, the surrounding mesenchyme condenses as the *dental sac*, which later forms the *cementum* and *periodontal ligament* C. THE BELL STAGE: with invagination of the enamel organ, the tooth assumes a bell shape 8. The mesenchymal cells in the dental papilla, adjacent to the inner enamel epithelium, differentiate into *odontoblasts*, which produce *predentin*, and deposit it adjacent to the inner enamel epithelium. The predentin later calcifies to form *dentin* 9. As the dentin thickens, the odontoblasts regress toward the center of the dental papilla but odontoblastic processes remain embedded in the dentin and are called *Tomes\' dentinal fibers or processes* 10. Cells of the inner enamel epithelium near the dentin form *ameloblasts*, which produce enamel in the form of prisms or rods over the dentin layer, thus help form the outer layer of the tooth or the *crown*. As enamel increases, the ameloblasts regress b. Thus, both enamel and dentin help create the crown, which begins formation at the cusp or tip of the tooth and progresses, in development, to the future root 11. The root begins after the enamel and dentin are well along in development c. The inner and outer enamel epithelia come together in the neck region and form an epithelial fold, the *epithelial root sheath*, which grows into the mesenchyme and begins the formation of the root d. The odontoblasts near the sheath form the dentin (continuous with that of the crown). As the dentin increases, the pulp cavity gets smaller and becomes a narrow canal for the vessels and nerves to enter the root 12. The inner cells of the dental sac form *cementoblasts* which produce *cementum*, which is deposited over the root dentin and meets the enamel at the neck of the tooth 13. As the teeth develop, the jaws ossify and the outer cells of the dental sac also become active in bone formation. Each tooth is soon surrounded by bone, except at its crown, and is held in its *bony socket or alveolus* by the periodontal ligament