The Integumentary System : Embryology & Genetic Bases. Purnomo Soeharso Department of Medical Biology FMUI

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1 The Integumentary System : Embryology & Genetic Bases Purnomo Soeharso Department of Medical Biology FMUI

2 Tissue organization of the skin (integumentum) : - Epidermis stratified epithelium on the outer surface - Dermis fibrous tissue beneath the epidermis - Subcutaneous layer loose connective tissue beneath the two layers, compose mostly of fatty tissues.

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4 Germ layer of origin : Epidermis specializes from surface ectoderm not involved in developing nervous system. Dermis differenciate from mesenchymal cells of mesodermal somites (dermatomes).

5 Cross section of 24 hr chick embryo, in primitive streak area

6 Epidermis Embryonic ectoderm originally a single sheet of cuboidal cells. Develop to become 2 layers in the 5th week : - periderm flatten cells in outer side (surface). - cuboidal basal cells reproductive cells give rise to new layers (periderm) above them. During 3 4 months epedermis consist of 3 cell layers : periderm intermediary stratum cuboidal basal cells

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8 After the 4th months the epidermis becomes stratified epithelia consist multiple layers of cells : - Stratum germinativum basal cells and their immediate descendants next above. - Stratum granulosum layer of cells next above stratum germinativum consist cells containing keratohyalin granules. - Stratum lucidum next above str. granulosum thin & clear cells containing degenerative keratohyalin. - Stratum corneum flat cells on the surface cell cytoplasm undergo cornification to become cornified dead cells with degenerate nuclei. The cornification is not intensive in some areas : red layer of lips & anus.

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10 Immigrant cells invading epidermis Epidermis consists of cells derived from ectoderm (proliferation of str. germinativum) and foreign cells from outside that migrate to epidermis during embryonic development and remain there in adult. Melanoblast derived from neural crest migrate to dermis & penetrate epidermis in the 3rd month. Melanoblast differenciate to form pigment granules (melanosomes) to become melanocytes. The pigmentation intensity varies among races although the number of melanocytes is not significantly different from race to race. The pigmentation is dependant on the activity of tyrosinase convert tyrosine to melanin.

11 Langerhans cells morphologically indistinguishable from keratinocytes (epidermal cells); however they are recognized by histochemical methods : - they have membrane bound ATPase - they have specific surface antigen different from epidermal cells. Derived from precursor cells in bone marrow. Migrate to epidermis and function as antigen presenting cells that process antigen entering epidermis. The antigen is fragmented and presented it to T-lymphocytes mediate cellular immune response to antigen.

12 Dermis Skin component underneath the epidermis compose of fibrous connective tissues. Develop from lateral wall of somites (left & right) dermatomes. The mesenchyme of dermatomes form collagen fibers and elastin fibers during the 4 6 months of pregnancy. The deepest layer of dermis subcutaneous layer loose & fatty connective tissues; contain capillary blood vessels & sensory nerve endings.

13 Cross section of 48 hr chick embryo in somite area

14 Cross section of 48 hr chick embryo, in somite area

15 Cross section of 10 mm pig embryo in back area

16 In some places the epidermis undergo modifications and develop into skin glands and hairs. The hair develop from epidermis that grow downwards into the dermis to become hair follicle. The messenchyme at the basal of follicle form hair papilla sorrounded by hair follicle root sheath. The cells in the germinal matrix proliferate & develop toward the surface & keratinized hair shaft..

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18 The sebaceous glands originate as buds from developing hair follicle root sheath grow into the surrounding tissue & branch to form several alveoli and their associated ducts. The central cells of the alveoli break down, forming an oily secretion sebum released to the hair follicle & passes to the surface of the skin. Sebaceous glands independent of hair follicles are found in some areas (e.g. in the glans penis & labia minora).

19 The sweat glands located throughout the body originate as downgrowths from the epidermis into the underlying mesenchyme (dermis). As it elongates, its end coils to form the primordium of secretory part of the gland. Eccrine sweat glands begin to function shortly after birth. Large apocrine sweat glands are mostly confined to the axilla, pubic, perineal regions and areolae of the nipples. These glands open into the upper part of hair follicles superficial to the openings of the sebaceous glands. They secrete only after puberty.

20 The mammary glands specialized sweat glands that develop as solid epidermal downgrowths into the underlying mesenchyme develop from thick strips of ectoderm extending from axillary to inguinal regions mammary ridges. Each primary bud give rise to several secondary mammary buds that develop into lactiferous ducts. Canalization of these buds is induced by placental sex hormones entering the fetal circulation. The gland is supported by fibrous connective tissues and fats that develop from the surrounding mesenchyme

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23 Tissue / cell culture of the skin The epithelial tissue/cells of the skin are potentially growth in vitro & prepared for various medical purposes : Advantageous for the replacement of skin damages (burns, wounds, etc). The tissues (grafts) are harvested from undamaged area of donor site : - autograft - isograft - allograft - xenograft

24 Skin allograft or xenograft can be used as temporary dressings rejected by the body (immune system) in a short time. Autograft & isograft are more acceptable recognized as self component by the body immune system. Epithelial grafts may be obtained by growing the keratinocytes in the laboratory.

25 The graft is cultured from a small piece of patient s own skin grow enough epithelial graft to cover 10 x 10 cm damage within 3 weeks. The individual grafts are typically multi layered cells much like epidermis. As the graft is placed on the acceptor (wounded) tissue the cells become increasingly differentiated. basal layer germinal layer top layer takes on the protective role of the skin by becoming cornified lining the surface.

26 Anomalies & genetic diseases of the skin 1. Congenital failure of normal differentiation skin retain its fetal character. - failure of pigment production/deposition in the epidermis albinism. - over abundant of pigment production melanism. - atypical pigmentation give pigmented spot (mole). - rough scaly skin due to abnormal cornification of superficial layers ichthyosis show thick plates of epidermis.

27 2. Acquired disease/abnormality. Xeroderma pigmentosum (xp) hypersensitivity to UV light & high incidence of UV induce skin cancer. Mutation leads to lack of enzyme necessary for excision repair of DNA. UV light characteristically cause thymine dimers the dimer should be excised by exonuclease leaving a portion of damaged DNA. Damaged DNA is repaired by DNA polymerase and DNA ligase to restore the continuity of DNA strand.

28 3. Genetic disease of the skin - Inherited from one generation to future generations - The inheritance may be in dominant or recessive heriditary fashion.

29 Keratosis piliaris (KP) Dry and worst pattern of skin chicken skin Inherited in autosomal dominant fashion Affected parent may inherits the disease to all or 50% of his/ her children.

30 KP may also manifest in patients due to : - Deletion of chromosome 18 - Translocation of 18p chromosome to Y chromosome - Involve LAMA I gene, situated in 18p locus express protein coded by 9.5 kb mrna.

31 Epidermolysis bullosa (EB) Rare genetic abnormality : 2/ in USA Abortion of skin due to abnormality of laminin 5 production/structure. Lead to destruction of collagen VII at the upper layer of dermis failure to maintain epidermis stabilization. Inherited in autosomal recessive fashion transmitted by healthy carrier of both parents.

32 Thank you for the attention & Happy Studying