The mechanisms which regulate gene expression are of major interest to geneticists as well as molecular, cellular and developmental biologists. It is well known that epithelial-mesenchymal interactions play a major role in the morphogenesis and biochemical differentiation of virtually all vertebrate organs; yet we know little about the relationships between gene expression and these ubiquitous tissue interactions. In the development of the skin, epidermal-dermal interactions are responsible for the formation and positioning of the numerous appendages which characterize the skin (i.e., hairs, feathers, scales, etc.) and the actual morphogenesis and biochemical differentiation (keratin synthesis) of each appendage.
Our aims i n this proposal are 1) to determine if the dermal components of different skin appendages can specifically direct keratin synthesis in an epidermis, 2) to determine if the three-dimensional shape of the dermis is related to its inductive ability, 3) to compare the biochemical and physical aspects of the proteoglycans present in normal dermis with those present in genetically defective dermises, 4) to analyze the cell surface carbohydrates in normal and mutant tissues, 5) to further characterize keratin profiles using our antisera to alpha and beta keratins and immunoreplica overlay techniques and finally 6) to analyze the tissue interactions in a genetic mutant known as avian """"""""ichthyosis."""""""" To accomplish our specific aims we will 1) employ two genetic mutants, 2) use tissue recombination and culture techniques, 3) use electrophoresis to determine keratin profiles, 4) use immunohistochemical and immunoreplica techniques and use standard biochemical procedures to analyze proteoglycans and cell surface carbohydrates. Knowledge of the mechanisms by which morphogenesis and biochemical differentiation are controlled is of particular significance to our understanding and eventual control of numerous skin disorders, including cancers, hyperkeratinizing conditions and genetic disorders.
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