THE RELATIONSHIPS AMONG ADHESION, STRATIFICATION AND DIFFERENTIATION IN KERATINOCYTES

Epidermis is a self-renewing, multilayered tissue composed primarily o f keratinocytes,The epidermal keratinocyte follows a terminal differen tiation pathway that under normal circumstances is tightly linked to i ts position within the epidermis and culminates in the formation of th e protective barrier (stratum corneum) that constitutes the outermost layer of skin, Strong but pliant adhesive mechanisms are essential for normal functioning of the epidermis, In the epidermis, adhesion is me diated primarily by four structures: hemidesmosomes and focal adhesion s, which function in cell-matrix adhesion, and desmosomes and adherens junctions, which function in cell-cell adhesion, In this review we co ncentrate on the transmembrane components of these structures, which a re thought to mediate directly the adhesive function, Members of the i ntegrin family of adhesion molecules comprise the transmembrane compon ents of hemidesmosomes and focal adhesions, although hemidesmosomes al so have a second, unrelated transmembrane molecule known as 'bullous p emphigoid antigen 2', Members of the cadherin family are the transmemb rane constituents of desmosomes and adherens junctions, Desmosomes con sistently contain two types of cadherins (desmoglein and desmocollin), while adherens junctions may contain only one type of cadherin (E- or P-cadherin), Expression of most of the transmembrane components varie s with the position of the keratinocyte within the epidermis and thus may reflect the degree of epidermal differentiation. All of the integr in subunits have been localized predominantly to the basal layer, In c ontrast, the cadherins show very complex expression patterns throughou t the epidermis, Desmogleins and desmocollins (the desmosomal cadherin s) are each encoded by three genes, and the expression of each gene is limited to certain epidermal layers. With respect to the cadherins of the adherens junction, it has been shown that E-cadherin is present t hroughout the epidermis, while P-cadherin is limited to the basal laye r, Interestingly, these complex expression patterns of integrins and c adherins within the epidermis may not simply be passive events in diff erentiation; rather, evidence is accumulating that adhesion molecules can exert a dynamic role in epidermal differentiation/stratification. For example, decreased adhesion to extracellular matrix, induced by ch anges in one or more integrins, appears to be a signal that induces ce rtain differentiation-related events. Even more profound effects on ep idermal morphogenesis have been demonstrated for the cadherins, E- and /or P-cadherin is required not only to initiate normal intercellular j unction formation but also for the subsequent development of a stratif ied epithelium, Thus, the findings to date with both integrins and cad herins suggest that adhesion molecules may function not just as direct mediators of adhesion, but also as regulators of epidermal stratifica tion, differentiation, and morphogenesis.