Embryonic Development of the Integumentary System PDF

OUTLINE I. INTRODUCTION II. EPIDERMIS A. 2nd Month B. 3rd to 5th Month C. Until End of 5th Month D. After the 5th Month III. CELLS OF THE EPIDERMIS...

OUTLINE I. INTRODUCTION II. EPIDERMIS A. 2nd Month B. 3rd to 5th Month C. Until End of 5th Month D. After the 5th Month III. CELLS OF THE EPIDERMIS Figure 1. The formation of the skin. A. Melanoblasts B. Melanocytes Two layers: C. Merkel Cells 1. Epidermis D. Langerhans Cells 2. Dermis IV. DERMIS A. Three Sources of Origin of the Mesenchyme B. 11th Week C. 3rd and 4th Months V. SKIN APPENDAGES A. Hair B. Nails C. Glands VI. MOLECULAR AND GENETIC BASIS OF SKIN DEVELOPMENT VII. CLINICAL CORRELATIONS A. Anomalies of Skin and Its Appendages B. Pigment Disorders C. Keratinization Defects D. Hair Distribution Abnormalities E. Other Skin Appendages Abnormalities VIII. DERMATOGLYPHS IX. MAMMARY GLANDS Figure 2. The layers and components of the skin. X. DEVELOPMENTAL ANOMALIES OF THE MAMMARY GLANDS XI. TIME TABLE OF THE DEVELOPMENTAL EVENTS II. EPIDERMIS Derived from the surface ectoderm I. INTRODUCTION Transformation begins at the cranial end of the fetus and proceeds caudally. Initially, single layered The Skin Largest organ in the body A. 2ND MONTH Functions: Presents two layers: ○ Barrier against infection (from the surroundings) 1. Periderm (Epitrichium) layer ○ Thermoregulation (controls body temperature) Superficial layer of flat cells made up of simple ○ Protects the body against dehydration squamous epithelium. Cells are desquamated & form part of the Derived from three diverse components: vernix caseosa (seen in developing fetus) 1. Surface ectoderm 2. Basal (Germinative) layer ○ give rise to layer and other components of the Deep layer of cuboidal cells human skin, including the epidermis Proliferate to form the 3rd intermediate layer 2. Underlying mesoderm Aka Stratum germinativum as these calls ○ give rise to the dermis proliferate to form the various layers of 3. Neural crest cells epidermis It can germinate other layers giving rise to 4 For dehydration, if a patient gets a 2nd degree or 3rd degree burn, more layers (interlayers) which are stratum chances of dehydration is high. That's why moistening cream will be corneum, lucidum, granulosum and spinosum applied or the patient will be bathed with saline so it can protect the *Vernix caseosa fluids and water of the patient from evaporation. Greasy yellow substance of peridermal cells + sebum (sebum + desquamated cells) Whitish sticky substance formed from mixture of hairs, shed off superficial layers of epidermis, and secretions of sebaceous glands Cover the skin of the newborn infant Protective function as it prevents the skin from maceration by amniotic fluid Page 1 of 9 [EMBRYOLOGY] 1.09 EMBRYONIC DEVELOPMENT OF THE INTEGUMENTARY SYSTEM – Dr. Steve S. Arellano, MD The epidermis will meet with the underlying layer - Dermis - to complete the full thickness of the skin D. After the 5th Month Periderm disappears as the cells are cast off into the amniotic fluid Periderm is replaced by stratum corneum Proliferation of stratum germinativum extends into the dermis as epidermal ridges (11th week to 18th week) Dermal epidermal boundary is not smooth, it is rugged. This gives rise to the grooves and ridges of the skin Finger and Palm Prints Grooves on the surface of palms of the hand, fingers, soles of the feet, and toes that are formed by epidermal ridges (result of the Figure 3. Vernix caseosa, a greasy substance, covering a newborn baby. irregularities of the dermo-epidermal junction Characteristic patterns: whorls, composite, loop and arch Patterns are genetically determined, and are different for each person. At birth, all the layers of adult epidermis are present Figure 4. Stage of the development of the skin B. 3RD TO 5TH MONTH Figure 5. Finger and palm prints Due to proliferation of cells, the epidermis becomes typical stratified squamous epithelium consisting of five layers: Stratum germinativum (Stratum basale) III. CELLS OF THE EPIDERMIS ○ consists of columnar cells (stem cells). They constantly divide mitotically and move A. Melanoblasts superficially to renew the epidermis. (Note: ○ dendritic cells of the epidermis the cells at this layer are the only dividing cells ○ derived from neural crest cells that detach from the in a normal epidermis) neural tube in the sixth week and migrate to the ○ It usually takes 6–8 weeks for the cells to move developing epidermis from the basal layer to surface of the skin ○ invade the stratum basale of epidermis (3rd month) Stratum spinosum ○ later they invade the dermo-epidermal junction & ○ consists of numerous irregular prickle cells become melanocytes (cells with spine-like processes). ○ dendritic cells are found in the nerve cells specifically ○ The spiny appearance of this layer is due to the neurites, which contain the axon and dendritic projection shape of the prickle cells (keratinocytes). Stratum granulosum B. Melanocytes (the pigment cells) Stratum lucidum ○ Came from primitive melanoblast ○ The cells that are superficial to granular layer ○ Represent between 5% and 10% of the cells of the with scanty nuclei, and form a homogeneous epidermis in the adult. layer. ○ Functions as a sunscreen, preventing solar radiation to ○ It exists only in lips and thick skin of the soles cause burns and cancer (long run), but may cause tumors and palms and cancer like melanoma. Stratum corneum ○ synthesize melanin pigments responsible for skin & hair ○ The horny layer consists of several layers of color flattened scale-like cells that are continuously ○ begin producing melanin before birth & distribute it to shed off as flake-like residues. epidermal cells ○ No nucleus ○ cell bodies are confined to basal layers of the epidermis ○ The cytoplasm of these cells is filled with ○ processes extend between the epidermal cells keratin granules. C. Until End of 5th Month Continuous keratinization, desquamation and replacement of peridermal cells by the basal layer Page 2 of 9 [EMBRYOLOGY] 1.09 EMBRYONIC DEVELOPMENT OF THE INTEGUMENTARY SYSTEM – Dr. Steve S. Arellano, MD Figure 6. Structure of a melanocyte Figure 8. Origin of dermis C. Merkel cells ○ appear at 8th to 12th weeks of IUL Three sources of origin of this mesenchyme: ○ uncertain origin 1. Dermatomes ○ associated with free nerve endings ○ give rise to the dermis on the dorsal aspect of the head & ○ Function: Mechanoreceptors (sense any deformity of the trunk skin, any compression and massive contact to the skin as 2. Lateral Plate Mesoderm well) ○ give rise to the dermis of the limbs & ventro-lateral of the ○ An example will be when you get slapped in the face, it trunk will give rise to lightning fast reaction 3. Neural Crest ○ give rise to the dermis of the head & anterior of the neck D. Langerhans cells ○ Mobile macrophage immune cells of the skin. 11TH WEEK: ○ appear at 8th and 12th weeks of IUL further thickening of the epidermis forms elevations called ○ derived from the bone marrow & migrate into the Epidermal Ridges epidermis This is the week where mesenchymal cells produce collagen and ○ involved in Ag presentation elastic fibers, giving the texture of the dermis or the skin its “elastic” ○ Function: Immunity and “squishy” texture The elastic texture also serves as protection to the body Dermis differentiates into two layers: 1. Papillary layer (superficial) 2. Reticular layer (deep) Figure 7. Cells in the epidermis Note: Ectoderm - epidermis Mesoderm - dermis Neural crest - meeting and converging of neural folds and neural crests forms the neural tube IV. DERMIS FIgure 9. The difference between thick and thin skin Derived from: a. Somatic mesoderm 3RD AND 4TH MONTH: b. Dermatomal mesoderm epidermis shows thickenings that project into the dermis c. Neural Crest Portions of dermis in between these projections from the dermal papillae Page 3 of 9 [EMBRYOLOGY] 1.09 EMBRYONIC DEVELOPMENT OF THE INTEGUMENTARY SYSTEM – Dr. Steve S. Arellano, MD B. NAILS Figure 10. Histological section of dermis with its different layers Figure 11. Nail Structure Nail Structures V. SKIN APPENDAGES 1. Germinal matrix Thick layer of cells formed from germinal layer Associated structures that are derived from the epidermis and Cells multiply and transform into the nail dermis that are located adjacent to the skin and serve a specific substance or nail plate (corresponds to function (ex: prevention of heat loss, sensation) Stratum lucidum of the skin) Hair, Nails, Glands 2. Eponychium Part of epidermis overlapping proximal part of A. HAIR nail plate Derived from the ectoderm 3. Hyponychium 12th Week Part of epidermis below the free margin of the ○ Germinal layer of the epidermis proliferates to form a nail cylindrical mass that grows down into the dermis ○ Lower end of this downgrowth (hair follicle) becomes C. Glands of the skin expanded and form the hair bulb 1. Sebaceous glands ○ Hair bulb will be invaginated by condensation of Located near the hair follicle mesoderm, which forms the papilla Function: waterproofing the surface for Germinal Matrix protection by secreting sebum ○ Formed from epithelial cells of the hair bulb 2. Eccrine sweat glands ○ Cells proliferate, grow toward the surface, keratinized, Present in deep dermis and form the hair shaft and internal root sheath Function: maintenance of body temperature External Root Sheath 3. Apocrine sweat glands ○ Formed from epithelial cells of the hair follicle Located near hair follicles in armpit, groin, ○ Continuous with the epidermis around nipple (dark area in the body) ○ (+) prominent basement membrane called the glassy Functions: membrane ○ Odor producing Mesodermal cells of the dermis surrounding the hair follicle form the ○ Sexual attractant (emotional) dermal root sheath and the arrector pili muscle Widely observed in First fine hairs, called lanugo hairs, are sloughed off at birth animals like dogs but not Arrector Pili Muscle the case for humans ○ Thin band of smooth muscle formed by mesodermal cells 4. Ceruminous glands ○ Gets attached to the dermal root sheath Present in external auditory canal ○ Typical hair follicle is thus formed Function: produce earwax serving protection ○ Its function is involved in the sensation on the skin, aids to ears by foreign bodies sticking to the the hair follicle for its movement to aid in the expression earwax, modulates sound of fear, excitement, or also angry and also when you’re 5. Mammary glands cold Function: secrete milk after parturition/ delivery Sebaceous Glands Bud arising from the ectoderm forming the wall of a hair follicle (epithelial root sheath) Bud grows into the dermis and divides into branches, the primordia of alveoli and ducts Central cells of alveoli degenerate and produce oily sebum that is release on too the surface of the skin; ○ Arrector Pili muscle Bundle of smooth muscle fibers that formed from the mesenchyme adjacent to hair follicle Page 4 of 9 [EMBRYOLOGY] 1.09 EMBRYONIC DEVELOPMENT OF THE INTEGUMENTARY SYSTEM – Dr. Steve S. Arellano, MD Attached to the dermal sheath of hair follicle C. Pax3 genes are active in neural crest cells migration & their and papillary layer of dermis differentiation into melanoblasts, melanocytes, & to start their function of producing melanin pigment Sweat Glands Two types of sweat glands: 1. Eccrine sweat gland - opens to the skin surface VII. CLINICAL CORRELATIONS 2. Apocrine sweat gland - opens to hair follicle A. Anomalies of Skin & its Appendages: Eccrine sweat glands Downgrowth from the epidermis into the dermis (20th weeks) 1. Aplasia: skin fails to develop in certain regions Downgrowth is at first solid, but later canalized to secrete oil and water material facilitating thermoregulation Lower end of the downgrowth becomes coiled and forms the secretory part Upper end is straight and forms the duct that opens in to the surface of the epidermis by sweat pore Start functioning at the time of birth Mechanism of secretion is merocrine Take part in temperature control Apocrine sweat glands Develop during puberty Seen in axilla, areola of nipples, pubic, and perineal areas Figure 14.. Neonatal with Aplasia cutis congenita Formed from hair follicles in the form of buds Open into the hair follicles 2. Dysplasia: congenital growths of the skin maldevelopment of various ectodermal derivatives (e.g. hair, teeth, sweat glands, & sebaceous glands) *KREMEN 1 Mutation ○ modulator of Wnt signaling ○ Responsible for ectodermal dysplasia (e.g. Oligodontia in Palestinian families) Figure 12.. Development of the sweat glands Figure 15.. Patients with KREMEN 1 Mutation B. Pigment Disorders 1. Albinism Absence (or reduced amount) of pigment in skin, hair & eyes - these cases are classified as different types of oculocutaneous albinism (OCA) melanocytes are unable to synthesize melanin AR genetic DSO skin is depigmented all over the body Figure 13. The skin and its Appendages. VI. MOLECULAR AND GENETIC BASIS OF SKIN DEVELOPMENT A. In the presence of Wnt signaling (Wingless & Int-1) & absence of response to Fibroblast Growth Factor (FGF) signaling the ectodermal cells express Bone Morphogenetic Proteins (BMPs), & become committed to develop into epidermis. B. Cells that are not responding to Wnt signaling may receive BMP and Figure 16. A child with albinism. FGF inhibitory signals from underlying mesenchyme thus facilitating development of skin appendages. 2. Vitiligo autoimmune DSO → loss of melanocytes Page 5 of 9 [EMBRYOLOGY] 1.09 EMBRYONIC DEVELOPMENT OF THE INTEGUMENTARY SYSTEM – Dr. Steve S. Arellano, MD presents as patchy loss of pigment that includes skin, hair, d. Harlequin fetus (AR) & oral mucosa which is NOT congenital ○ most severe form absence of pigment is patchy ○ diamond-like configuration of the (+) degeneration of already existing melanocytes scales results in a harlequin clown appearance Figure 17. Prominent figures with vitiligo. 3. Piebaldism AD genetic DSO patchy areas of absence of hair pigment (patches of white hair on forehead: white forelock) due to DSO development of melanocytes mutations in CD117 gene Figure 20. Infants with (1) Lamellar Ichthyosis (AR) and (2) Harlequin fetus (AR) D. Hair Distribution Abnormalities 1. Alopecia Figure 18. Patients with piebaldism Baldness resulting from an absent or faulty development of hair follicles 4. Waardenburg syndrome (WS) (+) defective migration & proliferation of neural crest cells (where melanocytes are derived) - absence of melanocytes derived from these cells in the stria vascularis in the cochlea accounts for deafness in these diseases from mutations in n Pax3 gene Features: a. White patches of skin & hair (usually forelock) b. Iris of different colors (heterochromia iridis) c. Deafness (due to loss of pigment cells in stria Figure 21. A man with alopecia. vascularis of cochlea) 2. Congenital alopecia Hair may be absent over the scalp Eyebrows and eyelashes may also be absent Figure 19. Characteristics of Waardenburg syndrome. C. Keratinization Defects Figure 22. A child with congenital alopecia. 1. Ichthyosis Hyper-keratinization of skin 3. Atrichia a group of hereditary disorders that are usually inherited Absence of hair in any part of the body as autosomal recessive trait but may be also X-linked Associated with other ectodermal defects (ex: teeth and nails) Resulting in non-inflammatory scaling, dryness, and cracks in the skin that form deep fissures Forms: a. Ichthyosis vulgaris (AD): Mildest form b. Lamellar Ichthyosis (AR) ○ “Collodion baby” ○ Infant is encased in translucent, taut, parchment-like membrane c. Epidermolytic hyperkeratosis (AD) Page 6 of 9 [EMBRYOLOGY] 1.09 EMBRYONIC DEVELOPMENT OF THE INTEGUMENTARY SYSTEM – Dr. Steve S. Arellano, MD Figure 23. A child with atrichia. 4. Hypertrichosis Excessive hairiness caused by an unusual abundance of hair follicles Figure 26. Four basic types of dermatoglyphic pattern in the digits Overgrowth of hair either localized in lumbar region covering spina bifida occulta or generalized It may be localized to certain areas of the body, especially the lower IX. MAMMARY GLANDS lumbar region covering a spina bifida occulta defect or may cover the entire body Modified sweat glands Develop from the mammary ridge Downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm) Canalization of these epithelial downgrowth will form: 1. Alveoli 2. Lactiferous ducts ○ Drain into an epithelial pit, the future nipple Figure 24. Characteristics of hypertrichosis. E. Other Skin Appendages Abnormalities 1. Anonychia Nails may be absent (underdeveloped) Occasionally show over development Figure 27. The formation of the mammary glands. Figure 25. Absent nails as characteristic of anonychia. VIII. DERMATOGLYPHICS Epidermal ridges produce typical patterns on the fingertips, palms of the hands & soles of the feet. Permanent Identification marks of an individual Patterns have genetic basis Uses: ○ Medico-legal investigation (establishing identity of an Figure 28. Parts of the A. Lactating breast, B. Lobule, C. Alveolus. individual) ○ Medical genetics Mammay line or ridge a. Establishing identity of an individual ○ Extend form the axilla to inguinal region b. chromosomal abnormalities (ex. Down’s ○ Appear at 7th week of development from root of UE Syndrome) (upper extremities) to root of LE (lower extremities) c. Medical condition (ex: CA, HPN, & mental ○ (+) Thickening of the ectoderm notably in the thoracic and illness) pectoral region Page 7 of 9 [EMBRYOLOGY] 1.09 EMBRYONIC DEVELOPMENT OF THE INTEGUMENTARY SYSTEM – Dr. Steve S. Arellano, MD ○ Thickened mass of epidermal cells projecting into the ○ Remain rudimentary dermis as primary bud Inverted Nipple (Crater Nipple) ○ From this thickened mass, 16-20 solid outgrowths arise, ○ Nipple fails to form resulting in lactiferous ducts opening and grow into the underlying dermis as secondary bud into a pit (instead of being elevated, it is depressed ○ Thickened mass of epidermis and the outgrowth gets forming a crater) canalized ○ Lactiferous ducts open into the original epithelial pit that Secretory elements (alveoli) of the gland are formed by proliferation has failed to evert of terminal parts of the outgrowths ○ Causes difficulty in suckling Each outgrowth forms one lactiferous duct Growth of underlying mesoderm pushes the wall outward, until it is elevated above the surface and forms the nipple by the time of birth XI. TIME TABLE OF THE DEVELOPMENTAL EVENTS Males: mammary gland remains rudimentary Females: ducts and secretory elements undergo extensive AGE DEVELOPMENTAL EVENTS development (at puberty and pregnancy (during and after)) 7th Week Mammary line is established 8th Week Melanoblasts start appearing 11th Week Epidermal ridges appear Collagen and elastic fibers appear 1st to 3rd month Cells of neural crest migrate to skin Before 2nd month Surface ectoderm is single layered 3rd month Melanoblasts invade epidermis 2nd to 4th month Surface ectoderm becomes multiple layered 3rd to 4th month Dermal papillae are formed, nail appear 5th month Development of eccrine sweat glands, rudiments of lactiferous ducts TEST YOUR KNOWLEDGE Figure 29. Development of mammary gland. A. Mammary ridge (left side) and 1. It is a natural biofilm that prevents the fetus’ skin from the maceration of the positions of accessory nipples (right side). B. Stages of development of amniotic fluid. It is composed of sebum and desquamated cells. mammary glands. A. Epitrichium layer B. Vernix caseosa C. Germinative layer X. DEVELOPMENTAL ANOMALIES OF THE MAMMARY GLANDS 2. It is an autosomal recessive trait that lacks tyrosinase enzyme resulting in melanin deficiency. 3. What developmental anomaly of the mammary glands is this? Differentiate Amastia the overlying defects. ○ Gland is absent on one or both sides Polymastia ○ Supernumerary breasts occur along the mammary ridge ○ Occurs when a remnant of the mammary line develops into a complete breast ○ From accessory mammary glands (away from the milk line) Gynecomastia ○ Excessive development of the male mammary glands ○ Male breast may even secrete milk ○ Associated with Klinefleter syndrome (47, XXY) Micromastia 4. These are epidermal ridges resulting from the irregularities of the ○ Gland is abnormally small dermo-epidermal junction, found on the palms and soles of the feet. Macromastia 5. What month do the eccrine sweat glands, rudiments of lactiferous ducts ○ Gland is abnormally large develop? Breast Hypertrophy 6. What is the epidermis formed mainly by? ○ Occur early in infancy A. Embryonic surface Ectoderm ○ 1-month old female infant B. Embryonic surface Endoderm Breast Hypoplasia C. Embryonic surface Mesoderm ○ Occurs asymmetrically when one breast fails to develop 7. Where are melanocytes derived from? completely A. Neural groove ○ 16-year-old female B. Neural pit Athelia C. Neural crest cells ○ Nipple is absent 8. By what week of formation are peridermal cells shed by? What does it form a Polythelia part of? ○ Supernumerary nipples is present anywhere along the A. 18 weeks, merkel cells milk line B. 21 weeks, vernix caseosa ○ accessory nipples have formed resulting from the C. 25 weeks, stratum corneum persistence of fragments of mammary line 9. Where is the dorsal dermis derived from? ○ may develop anywhere along the original mammary line A. Somatic (parental) layer of lateral plate mesoderm but usually appear in the axillary region Page 8 of 9 [EMBRYOLOGY] 1.09 EMBRYONIC DEVELOPMENT OF THE INTEGUMENTARY SYSTEM – Dr. Steve S. Arellano, MD B. The dermatome subdivision of the somites 10. What is the most severe form of ichthyosis? What inheritance pattern is it? A. Ichthyosis vulgaris (AD) B. Lamellar Ichthyosis (AR) C. Epidermolytic hyperkeratosis (AD) D. Harlequin fetus (AR) Answers: 1. B, 2. Albinism, 3. Polymastia (multiple breasts along the mammary ridge) and Polythelia (multiple nipples along the milk line), 4. Dermatoglyphics, 5. 5th month, 6. A, 7. C, 8. B. 9. B. 10. D. REFERENCES Sadler, T. W., et.al. (2019). Langman's medical embryology (14th ed.). Lippincott Williams & Wilkins. Arellano, S.S. PPT Lecture Page 9 of 9