Plakoglobin suppresses epithelial proliferation and hair growth in vivo.

Plakoglobin regulates cell adhesion by providing a modulatable connection b etween both classical and desmosomal cadherins and their respective cytoske letal linker proteins. Both plakoglobin and the related protein beta-cateni n are posttranscriptionally upregulated in response to Wnt-1 in cultured ce lls, Upregulation of beta-catenin has been implicated in potentiating hyper ; proliferation and tumor formation. To investigate the role of plakoglobin in these functions we expressed a full-length (PG) and an NH2-terminally t runcated form of plakoglobin (Delta N80PG) in mouse epidermis and hair foll icles, tissues which undergo continuous and easily observed postnatal renew al and remodeling. Expression of these constructs results in stunted hair g rowth, a phenotype that has also been observed in transgenic mice expressin g Wnt3 and Dvl2 (Millar et al., 1999), Hair follicles from PG and Delta N80 PG mice show premature termination of the growth phase (anagen) of the hair cycle, an event that is regulated in part by FGF5 (Hebert et al,, 1994). T he proliferative rate of the epidermal cells was reduced and apoptotic chan ges, which are associated with entry into the regressive phase of the hair follicle cycle (catagen), occurred earlier than usual.