Original Article

Plakoglobin Suppresses Epithelial Proliferation and Hair Growth In Vivo

Correspondence to: Pamela Cowin, Department of Cell Biology, New York University Medical School, 550 First Ave., New York, NY 10016. Tel:(212) 263-8715 Fax:(212) 263-8139/8752 E-mail:cowinp01{at}med.nyu.edu.

Plakoglobin regulates cell adhesion by providing a modulatable connection between both classical and desmosomal cadherins and their respective cytoskeletal linker proteins. Both plakoglobin and the related protein ß-catenin are posttranscriptionally upregulated in response to Wnt-1 in cultured cells. Upregulation of ß-catenin has been implicated in potentiating hyperproliferation and tumor formation. To investigate the role of plakoglobin in these functions we expressed a full-length (PG) and an NH₂-terminally truncated form of plakoglobin (N80PG) in mouse epidermis and hair follicles, tissues which undergo continuous and easily observed postnatal renewal and remodeling. Expression of these constructs results in stunted hair growth, a phenotype that has also been observed in transgenic mice expressing Wnt3 and Dvl2 (Millar et al. 1999 ). Hair follicles from PG and N80PG 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 ). The proliferative rate of the epidermal cells was reduced and apoptotic changes, which are associated with entry into the regressive phase of the hair follicle cycle (catagen), occurred earlier than usual.

Key Words: plakoglobin, ß-catenin, Wnt, cadherin, proliferation

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