The formation of the integument requires the interaction and integration of epithelial and mesenchymal cells to form skin and specialized skin appendages with unique functions such as hair and glands. Elucidation of this process is of central importance to the management of impaired skin conditions resulting from trauma, burn, grafts, auto-immune responses, genetics, chemotherapy, UV irradiation, and other causes. We have been using cultured embryonic skin explants as a model to analyze the roles of adhesion molecules in skin appendage morphogenesis. The general hypothesis is that adhesion molecules play specific roles in different developmental stages of skin appendages morphogenesis, and that they are downstream molecules of growth factors involved in epithelial-mesenchymal interaction. Previously we demonstrated unique temporal and spatial roles of NCAM and tenascin during skin appendage development. Here we propose to further analyze their roles through ectopically and untimely expression of these genes using the newly developed retroviral technology to produce """"""""transgenic skin"""""""" and """"""""chimeric skin explant"""""""". To search for signals that initiate skin appendage and induce adhesion molecules, a new model using epithelial-mesenchymal rotation/recombination was developed in which new induction occurs. This provide a sensitive model on which the roles of various growth factors and intracellular signaling modulators on epithelial-mesenchymal interaction can be tested. Furthermore, we have recently identified a new epithelial adhesion molecule, cDCC (chicken homologue to a gene deleted in human colo-rectal carcinoma), which is enriched in the proliferating basal layer and feather collar. We will characterize cDCC in skin development and analyze its function in skin appendage formation with antibodies and retroviral technology. The results will further our understanding in the mechanism of skin appendage formation and help to advance gene therapy which eventually may push the management of damaged skin or skin appendages to a new frontier. These findings will be applied to benefit those who suffer from abnormal skin conditions.
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