Desmosomal localization of beta-catenin in the skin of plakoglobin null-mutant mice

Plakoglobin, a protein belonging to the Armadillo-repeat gene family, is th e only component that adherens junctions and desmosomes have in common. Pla koglobin null-mutant mouse embryos die because of severe heart defects and may exhibit an additional skin phenotype, depending on the genetic backgrou nd. Lack of plakoglobin affects the number and structure of desmosomes, res ulting in visible defects when cells are subjected to increasing mechanical stress, e,g, when embryonic blood starts circulating or during skin differ entiation. By analysing plakoglobin-negative embryonic skin differentiation in more detail, we show here that, in the absence of plakoglobin, its clos est homologue, beta-catenin, becomes localized to desmosomes and associated with desmoglein, This substitution may account for the relatively late app earance of the developmental defects seen in plakoglobin null-mutant embryo s. beta-catenin cannot, however, fully compensate a lack of plakoglobin, In th e absence of plakoglobin, there was reduced cell-cell adhesion, resulting i n large intercellular spaces between keratinocytes, subcorneal acantholysis and necrosis in the granular layer of the skin. Electron microscopic analy sis documented a reduced number of desmosomes, and those present lacked the inner dense plaque and had fewer keratin filaments anchored. Our analysis underlines the central role of plakoglobin for desmosomal assembly and func tion during embryogenesis.