The dermal-epidermal junction (DEJ), or basement membrane rone, is the boundary between the epithelial and mesenchymal compartments of the skin; epidermal and fibroblastic cells in these two regions collaborate to synthesire its components. Ultrastructural studies (TEM and SEM) have defined a series of planes or layers (basal epidermal, lamina lucida, lamina densa, sublamina densa) and the morphology and density of attachment structures (hemidesmosomes, anchoring filaments, anchoring fibrils and anchoring plaques) in this region of normal skin. Change in structure of the DEJ provides information about the history of the tissue; reduplication of the lamina densa, for example, indicates a site of cell detachment or migration, or remodelling that accompanies repair of focal damage. In normal skin the structure of the DEJ is stable; in pathologic conditions it can be compromised by the congenital absence of certain structures or antigens (e.g., in the inherited disorders, epidermolysis bullosa [EB]) or by enzymatic degradation (e.g., in tumor invasion). Dissolution of the DEJ can also occur normally during the formation of epidermal appendages (e.g., hair follicles) and as melanocytes and Langerhans cells migrate into the epidermis during development.Biochemical and immunohisto/cytochemical studies have identified more than 20 molecules at the DEJ. These include well known matrix molecules (e.g., types IV and V collagen, laminin and fibronectin) and skin-specific antigens. The latter have been identified by autoantibodies or specific polyclonal or monoclonal antibodies raised against the skin, cultured cells and other epithelia. Some of the molecules of the DEJ are are present in basement membrane zones of many epithelia and thus are considered ubiquitous components (type IV, V, laminin, fibronectin, nidogen, entactin, HSPG, LDA-1, CSP [3B3]). All of them (that have been investigated in developing skin) appear ontogenetically as early as human embryonic tissue can be obtained and their expression is typically normal in patients with EB. The known properties of many of these molecules (particularly the matrix components) suggest functions they might impart to the DEJ: support of an epithelium (type IV collagen), regulation of permeability (heparan sulfate proteoglycan) or facilitation of cell attachment (fibronectin) and movement (laminin). Another group of matrix components and antigens of the DEJ includes molecules that are skin-specific or characteristic of stratified squamous epithelia (type VII collagen=LH 7:2 antigen, bullous pemphigoid antigen, AA3, GB3, KF-1,19-DEJ-1, epidermolysis bullosa acquisita antigen [EBA], AF-1 and AF-2, cicatricial pemphigoid antigen [CPA]) . These molecules are expressed in the DEJ later in development than the first group of molecules, in conjunction with the morphologic appearance of the structure they represent. Their appearance is also coordinated with specific developmental events (e.g., epidermal stratification) and the expression of molecules of differentiation in the epidermis and dermis. One or more of them is typically absent or reduced in expression in the skin of patients with heritable disorders affecting this region. There is no apparent correlation between the location of molecules in the DEJ and the stability of their expression.
Protein Destabilization as a Common Factor in Diverse Inherited Disorders
