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.

28. Adherens Junction

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