Cell adhesion and communication are interdependent aspects of cell behavior that are critical for morphogenesis and tissue architecture. In the skin, epidermal adhesion is mediated in part by specialized cell-cell junctions known as desmosomes, which are characterized by the presence of desmosomal cadherins, known as desmogleins and desmocollins. We identified a cadherin family member, desmoglein 4, which is expressed in the suprabasal epidermis and hair follicle. The essential role of desmoglein 4 in skin was established by identifying mutations in families with inherited hypotrichosis, as well as in the lanceolate hair mouse. We also show that DSG4 is an autoantigen in pemphigus vulgaris. Characterization of the phenotype of naturally occurring mutant mice revealed disruption of desmosomal adhesion and perturbations in keratinocyte behavior. We provide evidence that desmoglein 4 is a key mediator of keratinocyte cell adhesion in the hair follicle, where it coordinates the transition from proliferation to differentiation.
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We thank the family members for their interest and participation in this work. We appreciate discussions with Drs. David Owens, Ronald Liem, Akemi Ishida-Yamamoto, John Mc Grath, Abraham Zlotogorski, Howard Baden, Lloyd King, Elise Olsen, Lowell Goldsmith, and Cathy Mendelsohn. We thank Drs. Gary Struhl and Andreu Casali-Taberner for their generous help with confocal microscopy. We thank Andrew Engelhard, Karima Djabali, Marija Tadin, Hyunmi Kim, Kai Sun, Ming Zhang, Nancy Zhou, and HaMut Lam. This work was supported in part by USPHS NIH R01-44924 (AMC), K26-RR173 (JPS), P01 AR38923 (JU), R03 AR47938 (MGM), and the March of Dimes Birth Defects Foundation (AMC).