ABSTRACT
THE PROGRAM OF EPIDERMAL GROWTH AND DIFFERENTIATION The epidermis is a stratified squamous epithelium which covers the surface of our body. As such, it serves an important protective function, which it manifests by building an extensive cytoskeletal architecture composed of 10 nm keratin filaments. The mitotically active cells of the epidermis are tucked safely away in the innermost, i.e. basal layer, attached to an underlying basement membrane composed of extracellular matrix. Within this layer of cells are a population of stem cells, which periodically give rise to “transit amplifying” basal cells (Barrandon and Green, 1987). Putative stem cells in vitro express a higher level of β1 integrin on their surface than the transit amplifying basal cells that have a more limited lifespan (Jones et al., 1995; Hotchin et al., 1995). α3β1 integrin, which is activated by the ligand laminin V, is thought to be essential for the proper survival and functioning of the mitotically active keratinocyte (for review, see Watt et al., 1993). α6β4 integrin, which also uses laminin V as ligand, forms the core of the hemidesmosomes, which are specialized membrane plaque structures lining the base of basal epidermal cells in vivo. α6β4 differs from most integrins in that it connects to keratin filaments on its cytoplasmic surface. While the importance of α3β1 integrin has been underscored from cell culture studies, where few hemidesmosomes are formed, it is clear from gene targeting studies that in vivo, α6β4 play a key role in cellsubstratum attachment, a necessary feature for epidermal survival (Dowling et al., 1996; van der Neut et al., 1996; Georges-Labouesse et al., 1996). In vitro (Frisch and Francis, 1994) and in vivo (Dowling et al., 1996), when basal epidermal cells detach from their underlying basement membrane, they trigger the apoptosis program of cell death.
