[1.0] Embryology of the Integumentary and Musculoskeletal Systems.pdf

Y1B4M1L1 MUSCULOSKELETAL/ INTEGUMENTARY SYSTEM LECTURER: DR. JP GUZMAN OCTOBER 16, 2023 | 3:00 - 5:00 EMBRYOLOGY OF THE INTEGUMENTARY & MUSCULOSKELETAL SYSTEMS TABLE OF CONTENTS I. Integumentary System C. Molecular Regulation A. Skin 1. HOX Genes 1. Epidermis D. Vertebral Column 2. Dermis 1. Inter...

Y1B4M1L1 MUSCULOSKELETAL/ INTEGUMENTARY SYSTEM LECTURER: DR. JP GUZMAN OCTOBER 16, 2023 | 3:00 - 5:00 EMBRYOLOGY OF THE INTEGUMENTARY & MUSCULOSKELETAL SYSTEMS TABLE OF CONTENTS I. Integumentary System C. Molecular Regulation A. Skin 1. HOX Genes 1. Epidermis D. Vertebral Column 2. Dermis 1. Intervertebral Disc B. Hair III. Muscular System 1. Lanugo A. Striated Muscles C. Fingernails and Toenails B. Formation of Myotome D. Sweat Glands C. Molecular Regulation 1. Eccrine Glands D. Derivatives of Precursor 2. Apocrine Glands Muscle Cells 3. Breast 1. Epimere E. Mammary Glands 2. Hypomere 1. Polymastia E. Hypomere Derivatives II. Skeletal System F. Head Musculature A. Limb Growth G. Limb Muscles 1. Limb Bud H. Limb Musculature Development I. Cardiac Muscle B. Hyaline Cartilage J. Smooth Muscle Models ● After 4 months, it acquires its definitive arrangement as depicted in Figure 2. ○ The basal/germinative layer is responsible for the production of new cells. It also forms ridges and hollows. ○ The spinous layer is made up of large polyhedral cells with fine tonofibrils. ○ The granular layer contains small amounts of keratohyalin. ○ The horny layer is characterized as a tough scale-like surface of epithelium. It is composed of packed dead cells containing keratin. I. INTEGUMENTARY SYSTEM A. SKIN ● Skin - largest organ of the body. It has two components: ○ Epidermis - superficial layer → develops from surface ectoderm ○ Dermis - deep layer → develops from underlying mesenchyme EPIDERMIS ● At around 2 months of gestation, the epithelium divides into periderm/epitrichium. ● The intermediate layer is formed by the proliferation of the basal layer. Figure 2. Development of the skin after 4 months. ● The epidermis is invaded by neural crest cells at the 3rd month of life. ● At the period of neurulation, when the neural tube begins to form, the neural crest cells travel to its more definitive location. As these cells find their way into the skin, some of them will form into melanocytes. ○ Melanosomes, produced by melanocytes, are responsible for pigmentation. They are transported by the dendrites or dendritic processes of melanocytes and actively transferred to keratinocytes. ○ Filipinos have a lot of melanosomes in our skin, giving us brown coloration. DERMIS Figure 1. Development of the skin after 2 months. ● Derived from mesodermal layer coming from three parts: ○ Lateral Plate Mesoderm - develops into the dermis comprising the limb and the body wall. ○ Paraxial Mesoderm - develops into the dermis of the back. ○ Neural Crest Cells - develops into the dermis in the face and neck. ● In the 3rd and 4th month of life, the mesenchymal corium (found immediately after the basal cell layer of the epidermis) forms the dermal papilla. ○ The papilla are outgrowths or projections from the dermis extending to the level of epidermis. ○ It contains capillaries, blood vessels, and sensory nerve organs. ARANAS, BORRES, BUNGAY, GABATA, LABRADOR, PANIZA, REA, TUPAZ, VICTORIANO, VILLAVICENCIO | MG 8 1 of 7 Y1B4M1L1: EMBRYOLOGY OF THE INTEGUMENTARY AND MUSCULOSKELETAL SYSTEM LANUGO ● First hair to appear in newborns ● Shed at the time of birth which is much finer and replaced by coarser hairs from new hair follicles in the developing skin. Figure 3. Corium of the dermis (pointed by the line) ● The subcorium contains large amounts of fatty tissues. ○ In the more adult layer, the subcorium forms part of the level of the hypodermis, as well as the subcutaneous tissues. ● The vernix caseosa is a whitish paste which covers the skin among newborn. ○ Important for the protection against the macerated effects of the amniotic fluid in the uterus ○ Composed by secretions of sebaceous glands and degenerated epidermis. ○ The vernix will be very obvious in the immediate newborn and after a few days, it will slowly slap off. B. HAIR ● Epidermal proliferation that penetrates deeper into the dermis ● As the hair forms at its terminal ends, hair papilla is filled with mesoderm in which vessels and nerve endings develop ● Hair shaft (center of hair buds) – become spindle shaped and are keratinized ○ The hair shaft is the black part of the hair. ○ In other races, levels of melanin can affect hair color change but Filipinos generally have black hair. ● Epithelial hair sheath - surrounds the hair shaft Figure 5. Lanugo C. FINGERNAILS AND TOENAILS ● Fingernails and toenails are also epidermal appendages. ● Epidermal appendages begin to form as nail fields. ● Nail fields ○ Found at tips of the digits and of the developing limbs ○ As nail fields develop, nail roots become more evident ● Nail root ○ Found at the dorsal side of each digit growing proximally ● Fingernails and toenails ○ As they mature, growth begins to accelerate but does not reach the tips of the digits. ○ Growth is exponential until the 9th month of development. Figure 6. Formation of fingernails and toenails D. SWEAT GLANDS ● Sweat glands - epidermal in origin ● Two types: ○ Eccrine Glands ○ Apocrine Glands Figure 4. Development of a hair and a sebaceous gland. A. 4 months. B. 6 months. C. Newborn. ● The epidermis forms the hair bud, which slowly goes down to the dermis. ● At the center of the hair bud, the hair sheath forms with the hair papilla at its end. ● At the hair papilla, part of the blood vessels, capillaries, and nerve endings start to invade the mesodermal layer and begin to support at its base. ● Some of the appendageal glands begin to proliferate and surround the hair follicle ○ Particularly, the sebaceous gland and the smooth muscle cells. Figure 7. Eccrine sweat gland (left) and Apocrine sweat gland (right) ECCRINE GLANDS ● Abundant in the body ● Buds grow into dermis with coiled ends ○ It starts to form as buds which tends to grow at the dermis with the coiled ends ending or being secreted at the surface of the epithelium. ● Begins as buds in the epidermal germinative layer ARANAS, BORRES, BUNGAY, GABATA, LABRADOR, PANIZA, REA, TUPAZ, VICTORIANO, VILLAVICENCIO | MG 8 2 of 7 Y1B4M1L1: EMBRYOLOGY OF THE INTEGUMENTARY AND MUSCULOSKELETAL SYSTEM ● Functions by merocrine (exocytosis), their main function is for temperature control ○ In merocrine type, their secretion is by means of exocytosis, that means that most or none of the cells are being shed actively into the lumen. POLYMASTIA ● Polymastia is an abnormal development of the breast tissues ○ Bilateral formation or abnormal location of nipples, areola, and breast tissues. APOCRINE GLANDS ● Developed wherever there is body hair (abundant in the face, axilla, pubic region) ● Opens into hair follicles ● Contains lipids, protein, pheromones ● Apocrine secretion (portion of the cell is shed) ○ Apocrine secretion means that some or portions of the cell can be shed off into the lumen or is actively secreted. BREAST ● BREAST are modified sweat glands ○ Formed initially by mammary lines and mammary ridges E. MAMMARY GLANDS ● Mammary lines or ridges ○ Bilateral bands of thickened epidermis, extends from axilla to the hind limb (at around 6th - 7th week) ● Most of the line disappears, with persistence in the thoracic portion. ○ Thus, this is the common/normal location of the nipple areola breast complex. ● Remaining epithelium that does not degenerate, penetrates surrounding mesenchyme ● Epithelial sprouts canalized to form lactiferous ducts ● Lactiferous ducts initially drain into a pit which eventually proliferates to form the mouth, called the nipple from mesodermal tissues. ● Ducts form alveoli and secretory cells (through estrogen and progesterone) ○ As the ducts form to alveoli and secretory cells, it will branch extensively to form lobes and lobules, which is mediated by the hormones. Figure 9. A patient with polymastia. II. SKELETAL SYSTEM A. LIMB GROWTH ● In the 4th week of Gestation: ○ Limbs become visible as out-pockets in the ventrolateral body of the embryo. ○ Initially, limbs consists of mesenchymal core which arises from lateral plate mesoderm that will form bones and connective tissues → Lateral Plate Mesoderm - derivatives or products coming from the period of gastrulation. ○ Apical Ectodermal Ridge (AER) → Ectodermal thickening of limb → Induces cartilage and muscle development of the limb ■ AER also induces the adjacent mesenchyme to form a population of undifferentiated, rapidly proliferating cells. → Induces the zone of proliferation (Shown in Figure 10) Figure 10. Apical Ectodermal Ridge in embryo limb development LIMB BUD DEVELOPMENT Figure 8. Mammary glands development. The mammary line (shown on the right side) are common areas where the abnormal development of the breast tissues are found. Figure 11. Limb Bud Development ARANAS, BORRES, BUNGAY, GABATA, LABRADOR, PANIZA, REA, TUPAZ, VICTORIANO, VILLAVICENCIO | MG 8 3 of 7 Y1B4M1L1: EMBRYOLOGY OF THE INTEGUMENTARY AND MUSCULOSKELETAL SYSTEM HAND AND FOOT PLATES ● Divided into constrictions that enable the embryo to take peculiar limb features ○ 1st constriction → Divides into the forearm and the arm ○ 2nd constriction → Divides the forearm from the hand ● Fingers and toes are formed when cell death in AER separates them into five parts. ● Condensation of mesenchyme underneath will form cartilaginous digital rays ○ Death of intervening tissues forms the digits ● Any error in this development will form into congenital problems of syndactyly or polydactyly. ● Endochondral Ossification ○ Ossification of the bones of the extremities ○ This is the ossification process in which the cartilage is being invaded or formed into bones or is ossified. ● Primary Ossification Centers ○ Are present in the diaphysis of long bones by the end of the first trimester (around 12 weeks AOG). ● Chondrocytes form a cartilaginous model for the prospective bone ○ From the primary center of the diaphysis, endochondral ossification progress towards the cartilaginous ends ● At birth, diaphysis is completely ossified and epiphysis are still cartilaginous ○ Separated by the physis or the physeal plate ○ Importance of physis is highlighted in their large role in long bone development. Figure 12. Separation of the digits in the Handplates and the Footplates. (Note: Digits begin to separate once there is apoptosis of the intermittent tissues of the mesenchyme.) LOWER LIMB DEVELOPMENT ● Lower limb lags behind the upper limb by 1-2 days in development (cranio-caudal). ● Upper limbs rotate 90° laterally such that: ○ Extensor muscles will come to lie in its natural anatomical position, and the thumbs lie laterally ● Lower limbs rotate 90° medially such that: ○ Extensor muscles of the thighs and legs will lie anteriorly, and the big toe lie medially B. HYALINE CARTILAGE MODELS ● Chondrocytes foreshadow the bones on extremities, particularly its development. ○ They support the ossification centers ● Mesenchyme in the underlying bud condense to form chondrocytes ○ Chondrocytes form a scaffolding, which would eventually lead to the ossifications. Figure 14. Endocondrocyte Ossification C. MOLECULAR REGULATION ● Molecular regulation of skeletal development includes: HOX GENES ● Influences positioning of limbs along craniocaudal axis in flank regions ● Determinants of limb development and variation of forelimb and hindlimb ● Regulates the types and shapes of bones of the limb ○ Limbs now take the appearance of its adult counterparts. ● Proteins and Growth factors involved: ○ Fibroblast growth factor-10 (FGF-10) induces limb outgrowth from mesoderm ○ Bone morphogenic proteins (BMP) induce AER formation ○ Radical fringe genes restricts location of AER into dorsal tip of limbs for lengthening ○ FGF-4 and FGF-8 maintain progress zone with proliferation of mesenchyme in the ridge D. VERTEBRAL COLUMN Figure 13. Hyaline Cartilage Models in Bone Development ● Around the 4th week of gestation: ○ Sclerotomes shift position to surround both spinal cord and notochord → This is evident in gastrulation ○ Intersegmental arteries separate sclerotomic blocks ARANAS, BORRES, BUNGAY, GABATA, LABRADOR, PANIZA, REA, TUPAZ, VICTORIANO, VILLAVICENCIO | MG 8 4 of 7 Y1B4M1L1: EMBRYOLOGY OF THE INTEGUMENTARY AND MUSCULOSKELETAL SYSTEM ○ Mesenchymal cells between blocks do not proliferate but fill space in between two precartilaginous vertebral bodies to form the intervertebral disc. B. FORMATION OF MYOTOME 1. 2. 3. 4. Dorsomedial muscle cells will migrate ventral to the myotome Dermatome is formed Myoblasts form and fuse to give rise to multinucleated fibers Myofibrils appear and will have cross striations which are typical of skeletal muscle development Figure 15. Vertebral Column development. ● In Figure 15: ○ (A) Intervertebral disc separates the sclerotomic blocks, whereas the segmental arteries supply blood to the vertebral column ○ (B) Further maturation leads to the formation of: → nucleus pulposus → annulus fibrosus of the intervertebral disc ○ (C) Shows the mature form of the vertebra. → Mature vertebrae are completely ossified → Intervertebral discs in between the spaces where the intersegmental arteries enter. INTERVERTEBRAL DISC Figure 16. Formation of Myotome ● Nucleus pulposus ○ Part of the notochord that persists in the region of the intervertebral disc ● Dense Annulus fibrosus ○ Surrounds softer nucleus pulposus ● Intervertebral disc is important for the support and cushioning of the vertebral column. ● Rearrangement of the definitive vertebra causes myotome to bridge the intervertebral disc. ● Intersegmental arteries at first lying between sclerotomes now pass midway over the vertebral bodies. C. MOLECULAR REGULATION III. MUSCULAR SYSTEM ● BMP-4 and FGF (from lateral plate mesoderm) together with WNT proteins signal dorsolateral cells to express muscle specific gene called MYO-D ● MYO-D family genes - act as transcription factors to regulate downstream genes, particularly in the muscle differentiation pathway D. DERIVATIVES OF PRECURSOR MUSCLE CELLS ● Prospective muscles cells will form into two groups, namely: ○ Epimere ○ Hypomere ● Consists of three types: ○ Skeletal muscle - derived from paraxial mesoderm ○ Smooth muscle - derived from splanchnic mesoderm ○ Cardiac muscle - derived from splanchnic mesoderm A. STRIATED MUSCLES ● Arise from somites and somitomeres from the musculature of the axial skeleton ● Somites will differentiate into: ○ Sclerotome ○ Dermatome ○ Two muscle forming regions: → Dorsolateral region - gives rise to limbs → Dorsomedial region - will migrate ventral to the dermatome to give rise to the myotome Figure 17. Derivatives of Precursor Muscle Cells ARANAS, BORRES, BUNGAY, GABATA, LABRADOR, PANIZA, REA, TUPAZ, VICTORIANO, VILLAVICENCIO | MG 8 5 of 7 Y1B4M1L1: EMBRYOLOGY OF THE INTEGUMENTARY AND MUSCULOSKELETAL SYSTEM EPIMERE ● Smaller dorsal portion ○ Supplied by: the the dorsal rami nerves ● Nerves innervating segmental muscles of this portion will divide into → dorsal primary ramus ● Myoblasts of the epimere will form → the extensor muscles of the vertebral column HYPOMERE ● Larger ventral portion ○ Supplied by: the ventral rami nerves ● Nerves innervating segmental muscles of this portion will divide into → ventral primary ramus ● Myoblasts of the hypomere will give rise to → limbs and body wall muscles E. HYPOMERE DERIVATIVES ● Cervical ○ Scalene ○ Geniohyoid ○ Prevertebral muscles ● Thoracic ○ External intercostal ○ Internal intercostal ○ Innermost intercostals ○ Transversus thoracis ● Abdominal ○ External oblique ○ Internal oblique ○ Transversus abdominis ● Lumbar ○ Quadratus lumborum ○ Pelvic diaphragm ○ Anus F. HEAD MUSCULATURE ● All voluntary muscles of the head are derived from paraxial mesoderm ○ Includes tongue, eye (except the iris, which comes from the optic cup), and pharyngeal arches ● Patterns of muscle formation in the head are directed by elements from neural crest cells. G. LIMB MUSCLES ● Mesenchyme derived from dorsolateral cells of somites that migrate to the limbs ● Splits in two extensor and flexor groups as limb elongates H. LIMB MUSCULATURE ● Upper limb buds lie opposite the lower five cervical and the upper two thoracic segments. ● Lower limb buds lie opposite the lower four lumbar and upper two sacral segments. ● Radial nerve - supplies extensor muscles by fusion of dorsal segmental nerve branches. ● Ulnar and median nerves - supply the flexor muscle components, and comes from the fusion of the combination of the ventral nerve branches. ● Spinal nerves - play an important role in motor and sensory innervation. Figure 18. Derivatives of Precursor Muscle Cells I. CARDIAC MUSCLE ● Develops from splanchnic mesoderm surrounding heart endothelium. ● Myoblasts adhere to one another to form intercalated discs. ● Purkinje fibers - forms the conducting system of the heart. J. SMOOTH MUSCLE ● Forms smooth muscles of the gut and blood vessels. ● Also comprise the following: ○ Sphincter and dilator muscles of the pupils ○ Muscle tissue of the mammary glands ● All are derived from splanchnic mesoderm IV. REVIEW QUESTIONS 1. Which layer? A. B. C. D. layer of the skin is formed by the proliferation of the basal Ectoderm Periderm Mesenchyme Intermediate layer 2. These are projections from the dermis which consists of capillaries, blood vessels, and sensory nerve organs. A. Neural crest cells B. Mesenchymal corium C. Dermal papilla D. Subcorium 3. Which glands develop wherever there is body hair? A. Eccrine glands B. Apocrine glands C. Endocrine glands D. Exocrine glands 4. This is the ossification process in which the cartilage is being invaded or formed into bones or is ossified. A. Primary Ossification B. Endochondral Ossification C. Intramembranous Ossification D. Diaphysis 5. These structures are found in between the spaces where the intersegmental arteries enter, and are important for the support and cushioning of the vertebral column. A. Sclerotomes B. Dermatomes C. Notochord D. Intervertebral discs ARANAS, BORRES, BUNGAY, GABATA, LABRADOR, PANIZA, REA, TUPAZ, VICTORIANO, VILLAVICENCIO | MG 8 6 of 7 Y1B4M1L1: EMBRYOLOGY OF THE INTEGUMENTARY AND MUSCULOSKELETAL SYSTEM 6. They induce the formation of the apical ectodermal ridge (AER) or the ectodermal thickening of the limb. A. Bone morphogenic proteins (BMP) B. Fibroblast growth factor-10 (FGF-10) C. Radical fringe genes D. MYO-D family genes 7. Myoblasts of the _____ will give rise to the limbs and body wall muscles. A. Epimere B. Hypomere 8. All voluntary muscles of the head are derived from which layer of the mesoderm? A. Lateral plate mesoderm B. Neural crest cells C. Paraxial mesoderm D. Splanchnic mesoderm 9. It supplies the extensor muscles by fusion of dorsal segmental nerve branches. A. Spinal nerve B. Radial nerve C. Ulnar nerve D. Median nerve 10. It is the bilateral formation or abnormal location of nipples, areola, and breast tissues. A. Polymastia B. Vernix Caseosa C. Gynecomastia D. Fibroadenoma Answers: 1D, 2C, 3B, 4B, 5D, 6A, 7B, 8C, 9B, 10A References: Guzman, J.P. (2023). Integumentary System Embryology Online Lecture. Guzman, J.P. (2023). Musculoskeletal System Embryology Online Lecture. ARANAS, BORRES, BUNGAY, GABATA, LABRADOR, PANIZA, REA, TUPAZ, VICTORIANO, VILLAVICENCIO | MG 8 7 of 7