dermoepidermal junction is the main interconnecting supporting strucure binding the Epidermis and Dermis together

1. By
Dr. RANJAN DASH

2. DERMATOLOGY
 GREAT SAYING :

3. HEADS TO BE HIGHLIGHTED
DEFINITION
ORIGIN AND DEVELOPMENT
FUNCTION
ULTRASTRUCTURE
UBIQUITUOUS COMPONENTS OF DEJ
APPLIED ASPECTS
RECENT ADVANCES

4. DEFINITION of DERMO-EPIDERMAL
JUNCTION /DEJ
“A highly complex form of basement membrane that
underlies the basal keratinocytes of epidermis and
extend into the upper layer of dermis”.
 A critical interface/junction between the
overlying epidermis and underlying dermis.
 It is continuous along the epidermis and skin
appendages .

5. GROSS VIEW OF DEJ IN A SKIN SECTION

6. ULTRASTRUCTURE OF DEJ
LAMINA LUCIDA
• Tonofilaments
• Hemidesmosomes
• Anchoring
filaments
• Laminin
• integrins
LAMINA DENSA
• Type4 collagen
• Laminin
• Nidogen/entactin
• Heparan sulfate
RETICULAR
LAMINA(SUB-
BASAL LAMINA)
• Anchoring fibrils
• Reticular fibres
• Oxytalan fibres
• Elaunin fibres

7. The BMZ can be
recognized
histologically by
positive
labelling with Periodic
AcidSchiff Stain.
Electron microscopy
is an essential
technique to reveal
the ultrastructure
morphology of
basement
memberane zone.

8. ORIGIN & DEVELOPMENT
Structures of basal lamina (lucida & densa) : ectodermal origin
Structures of sub-basal-lamina(fibroreticular
lamina):mesodermal origin.
 As early as 8 weeks EGA ,a simple Basement membrane
separates the epidermis from dermis,comprising of all basic
ubiquituous components : Laminin 111,collagen IV,Heparan
sulfate and Nidogen.
Components of hemidesmosomes and anchoring filaments and
fibrils develop around the start of early embryonic period(3-5m).

9. ZONE 1 : LAMINA LUCIDA AND
ITS COMPONENTS
Tonofilaments: keratin intermediate
filaments, keratin 5,14 that course through basal
keratinocytes into the hemidesmosomes.
Hemidesmosomes: are anchoring junctional
proteins, extend from the intracellular
compartment of the basal keratinocytes to the
lamina lucida inthe upper portion of the dermal–
epidermal basement membrane.

10. Hemidesmosomes cont.
Also constitute the hemidesmosome–anchoring filament complex.
 HD1 to HD5 with molecular masses of approximately 500, 230, 200, 180
and 120 kD, respectively.
 HD 1 corresponds to plectin, a large intracytoplasmic adhesion
molecule.
 HD2 and HD4 as the 230 and 180 kDa bullous pemphigoid antigens (BPAG1
and BPAG2).
 HD 3 & HD 5 corresponds to α6 and β4 chain of integrin molecule .
 BPAG 2 also known as type XVII collagen, interacts with α6β4 integrin
and extends from the intracellular compartment of basal cells to the
extracellular space, thus stabilizing the association of basal
keratinocytes to the underlying basement membrane.

12. Lamina lucida components cont.
Anchoring filaments : are thread‐like structures
that complex with hemidesmosomes.laminin 332 may
be the major component of the anchoring filaments.
The cell binding of laminins is mediated by

13. LAMININS
 High MW glycoproteins(400-900).
 Important part of basal lamina that help in cell adhesion,cell
differentiation and migration.
 Structurally ,a trimer of 3 polypeptide chains with varying orientation.
 Nomenclature as per constituent chains
 ex : laminin 511 contains α5 ,β1 and γ1 chains.
 Laminins are associated with typeIV collagen via entactin and perlecan.
 Also bind to cell membranes via Integrin receptors.
 and muscle membrane via dystroglycan molecules.

15. DISTRIBUTION OF LAMININ
As many as 16 different laminins have been identified thus far
and at least four of them are physiologically present in the
skin in significant quantities.
Type of
laminin Polypeptide Distribution
111 α1β1γ1 Blood vessels, LD
311 α3β1γ1 LL/LD
511 α5β1γ1 LL/LD
332 α3β3γ2 Interface of LL/LD

16. INTEGRIN
Transmembrane glycoproteins that attach cell-cell or
cells to extracellular matrix.
Bind to ligands such as fibronectin,vitronectin,collagen
and laminin.
Structurally heterodimers of α and β peptide chains.

17. INTEGRIN LIGAND DISTRIBUTION
 α5β1 fibronectin ubiquitous
 α6β1 laminin ubiquitous
 α7β1, laminin muscle
 α1β2 Ig superfamily white blood cell
 α2β3 fibrinogen platelet
 α6β4 laminin hemidesmosome

18. Components of
lamina densa
COLLAGEN Type IV
 A heterotrimer of three α polypeptide chains
.
 Each of these chain contain 3 distinct domains
: 1) N-terminalcysteine-rich 7-s domain
2) a central triple-helical domain and
3) a C-terminal globular domain (NC-1) .
Covalent interactions among 7-s region form
specialised network forms esp. a four-legged
Spider form
** α1 and α2 are ubiquitous but the third
chain can be α3 or α4 or α5 in different
basement membranes .

19. NIDOGEN/ENTACTIN
 ARE SMALL glycoprotein
MOLECULES EXPRESSED AS
NIDOGEN 1 AND NIDOGEN 2
CONNECTING LINK BETWEEN
COLLAGEN IV AND LAMININ ,
 FURTHER IT INTEGRATE
OTHER COMPONENTS OF
BASEMENT MEMBRANE SUCH
AS PERLECAN, FIBULIN .

20. HEPARAN SULFATE proteoglycan
Three major types present in vascular and epithelial
basement membrane: 1)perlecan 2) agrin
3)collagenxviii
- Perlecan in basement membrane of myocardium and
skin,
- Agrin in neuro muscular junction and renal tubular
basement membrane.
- Collagen xviii : considerd a hybrid collagen-
proteoglycan present over glomeluar basement
membrane allowing selective permeability.

21. COMPONENTS OF SUBLAMINA DENSA
Anchoring fibrils :
 condensed filamentous aggregate of type VII collagen.
 proximal end (NC-1 domain) insert into basal lamina-laminin 332
 distal end integrate into fibrous network of dermis or electron dense
amorphous anchoring plaques(TYPE IV COLLAGEN)
 Anchoring fibrils form a scaffold that entraps large number of dermal fibrils
 Bind them with covalent crosslinking between collagen vii and collagen 1
,securing the lamina densa to the subjacent dermis .

22. ANCHORING FIBRILS

23. APPLIED ASPECTS
BIOPSY : Evaluation of inflammation and change in tissue architecture at the
level of dermoepithelial junction.
SPLIT SKIN METHOD : splitting of skin through lamina lucida,so as to
distinguish the distribution of immune deposits at epidermal & dermal
level .methods used are : 1) enzymatic via Trypsin ,dispase
2)NACL Splitting: incubation in 1 M NS at for 24-48 hr.
TRANSMISSION ELECTRON MICROSCOPY : to ascertain the architectural
details of epidermis ,DEJ and dermis .
DIF(DIRECT IMMUNOFLUOROSCENCE) and IF (INDIRECT
IMMUNOFLUOROSCENCE) study : to determine the type of immune
deposits and the sites of distribution ,i.e. at epidermal,subepidermal/BMZ
or at upper dermis.

24. DEJ/BMZ TARGETS IN
SKIN DISEASE
STRUCTURAL
LEVEL
COMPONENT
MOLECULES
AUTOIMMUNE
TARGET
GENETIC
TARGET
TONOFILAMENT KERATIN 5,14 EBS
HD PLAQUE BPAG 1
PLECTIN
BP
BP,CP
EBS
EBS-MD,JEB-PA
HD TRANS-
MEMBRANE
PROTEI N
COLLAGEN XVII
α6β4
BP,CP,LAD,PG
BP ,CP
JEB-non-Herlitz
JEB- PA
ANCHORING
FILAMENT
LAMININ332
ECTODOMAIN OF
COLLAGEN XVII
CP
BP, LAD
JEB-Herlitz
JEB-nonlethal
ANCHORING
FIBRILS
COLLAGEN VII EBA DEB