Epidermopoeisis - development of skin
- 1. EPIDERMOPOEISIS Dr. Kriti Maheshwari 1st year Resident
- 2. • The epidermal thickness, the number and size of epidermal cells remain constant, with the rate of cell production matching the rate of cell loss. • 3 populations of cells exist in the basal layer: -Stem cells. -Transient amplifying cells -Post mitotic cells.
- 3. • Keratinocyte stem cells give rise to all the layers of the epidermis, with the majority of these cells committed to terminal differentiation. • Stem cells have a large capacity for proliferation. They are present in the basal interfollicular epidermis and bulge region of follicles. • A transient amplifying cells can undergo a limited number (up to 5 to 6 times) of mitotic divisions.
- 4. Cell Cycle Multiplying cells go through 4 phases of the cell cycle : • M - Mitotic phase of division. • G1- post mitotic phase or interphase. • S - phase of DNA synthesis • G2 - Premitotic phase or short resting phase. • G0 - quiescent phase
- 5. Mitotic index – Fraction of cells in mitotic phase at any given time. Labelling index – Fraction of basal cells in DNA synthesis phase
- 6. • The time taken by keratinocytes to pass from the basal layer to the stratum corneum and the skin surface is called the epidermal turnover time. • It is approximately 52-75 days. • The approximate transit time from the basal layer to stratum corneum is 12 to 19 days. • Transit time through the stratum corneum is 14 days.
- 7. Regulation of Epidermopoeisis A. Stimulatory factors : Human epidermal growthfactor(EGF) Transforming growth factor(TGF α) Amphiregulin IL-1,IL-2,GM-CSF BasicFGF Keratinocyte growthfactor(KGF) Vitamin A
- 8. - Epidermal growth is inhibited by negative feedback mechanism. B. Inhibitory Factors : IFN α IFN γ TNF α High calciumlevel
- 9. C. Apoptosis : programmed cell death - A major cellular homeostatic mechanism in the skin. - Terminal differentiation of epidermal keratinocytes occurs by modified apoptotic programs.
- 10. D. Signal transduction pathways : - It is a mechanism by which signals from outside the cells, such as hormones combine with cell receptors intracellularly to regulate the cell growth. - These include growth factors, cyclic AMP, protein kinase C, inositol phosphate and protein tyrosine kinase.
- 11. E. Integrins : They serve as a physical link between matrix molecules (collagen, laminin, fibronectin) and cytoskeleton of keratinocytes and act as a route of bidirectional communication that can result in change of gene expression, pH and calcium fluxes.
- 12. Epidermal Differentiation After detaching from the basal lamina, epidermal keratinocytes move from the basal layer towards the skin surface, undergoing terminal differentiation to produce the stratum corneum. This involves the formation of keratins (insoluble proteins) by keratinization.
- 13. Keratin Filamentous cytoskeleton of all mammalian cells including epidermal keratinocytes. Contains: • Actin containing microfilaments 7nm in diameter. • Tubulin containing microtubules 20- 25 nm in diameter. • Intermediate filament 7-10nm in diameter. More than 30 keratins have been
- 14. - 54 functional keratingenes. - Two gene family:- type 1(basic) - 1 to 8 type 2(acidic) - 9 to 19 - Retinoic acid, growth factors ,hormones regulate keratingene expression.
- 15. Simple epithelia K8/K18 Stratified squamous epithelia (Basal) K5/K14 Suprabasal K1/K10 Cornea K3/K12 Buccal Mucosa K4/K13 Nails K6/K16 Liver K8/K18
- 16. Keratohyaline granules They are the distinctive cellular inclusions in differentiating epidermis. Seen in keratinocytes of SG. The granules have amorphous, phosphate containing material rich in histidine, which disappears as keratinocytes enter SC. The granules are composed of profilaggrin, keratin filaments and loricrin.
- 17. Filaggrin k/a filament aggregating protein. Histidine rich, cationic protein. Filaggrin is degraded into molecules which further help in hydration of SC and help filter UV radiation. Loricrin : Cysteine rich protein that is a major component of the cornified envelope.
- 18. Lamellar granules/ Odland Bodies Contain phospholipids, glycolipids and free sterols. The lamellar granules fuse with the plasma membrane to discharge their contents into intercellular space, forming a barrier to permeability. Found adjacent to the upper part of SS and in the SG.
- 20. Cornified Envelope Highly insoluble cell envelope. Involucrin : best established precursor. Formation triggered by intracellular Ca. Present in SC Other precursors – i. Loricin ii. Cornifin iii. Periplakin iv. Envoplakin v. Pancornulin vi. Elafin
- 21. Keratinocyte Integrins These are transmembrane cell surface glycoproteins that form receptors to mediate adhesion in both intercellular and cell substrate interaction. During differentiation keratinocytes lose adhesions to the matrix by loss of integrin expression.
- 22. Intercellular Junctions They link adjacent keratinocytes and are responsible for mechanical, biochemical and signalling interactions between cells. Components are : a) Desmosomes b) Adherens junctions c) Gap junctions d) Tight junctions
- 23. Desmosomes Specialised regions of the plasma membrane that link cells to each other and also connect intermediate filaments (tonofilaments) to plasma membrane. Provides network of stability in the epidermis. Ultrastructure : cell membrane of two adjacent cells forms a symmetrical junction with a central intercellular space of 30 nm containing a dense line.
- 24. Components of desmosomes : a) Cadherins : 1. Desmogleins (Dsg) 2. Desmocollins (Dsc) They are transmembranous calcium rich glycoprotein. b) Plakins – desmoplakin, plakoglobin, plakophilin, envoplakin and periplakin
- 25. • The intercellular parts of glycoproteins are attached to keratin filament network via desmoplakin, plakoglobin and other macro molecules. • Desmosomal proteins acts as autoantigen in various immunobullous blistering disorders.
- 26. Adherens Junction Electron dense , transmembrane structures that engage with actin skeleton. The main linkage to actin cytoskeleton is through α catenin which organizes the entire multiprotein complexity of adherens junctions and in determining actin binding polymerization activities.
- 27. They contribute to- epithelial assembly, adhesions, barrier formation, cell motility and changes in cell shapes. Comprise of two basic adhesive units: I. Nectin – afadin complex. II. Cadherin complex.
- 29. Gap Junction Clusters of intracellular connections knows as connexins. Allow transfer of ions and small molecules (<1000 Da). Connexons originate following assembly of six connexin subunits within the Golgi network that are then transported to the plasma membrane.
- 30. Divided into 3 groups - (α, β and γ). Stability of gap junctions is mediated by protein kinase C, calmodulin , calcium, cyclic adenosine monophosphate (cAMP) and local pH. Gap junction communication is essential for cell synchronization, differentiation, growth and metabolic coordination of avascular organs, including epidermis.
- 32. Tight Junctions Major regulators of permeability of epithelia. Main component of skin barrier integrity. The principal structural proteins of tight junctions are the claudins, transmembranous proteins - junctional adhesion molecules (JAMs) and the occludin group of proteins. The main claudins in the epidermis are claudin 1 and 4.
- 33. Transmembranous proteins do not bind to one another but the claudins and occludins can bind to the intracellular zonula occudens proteins ZO-1, ZO-2, ZO-3.
- 34. Applied Aspects Pemphigus vulgaris – antibodies against Dsg 3. Pemphigus foliaceus – antibodies against Dsg 1. SSSS – bacterial exotoxin cleaves the extracellular domain of Dsg 1. Harlequin Ichthyosis – filaggrin is absent and low level expression of K1/10.
- 35. Restrictive dermopathies – down regulation of K1/10 and abnormal keratohyaline granules. Keratinocyte culture can be used for skin grafting in burns and other skin defects Psoriasis – epidermal turnover time reduces to 8-10 days. Ichthyosis vulgaris – due to defect in profilaggrin/filaggrin.
- 36. Non keratinocytes of the epidermis Melanocytes and Langherhans cells, which migrate into the epidermis during embryonic development. Merkel cells develop in situ from the ectoderm. Melanocytes and merkel cells – basal layer. Langerhan cells – suprabasal layer.
- 37. THANK YOU