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Role of Rho GTPases in epidermal keratinocyte stem cell fate. Implication in skin morphogenesis and in the development of skin cancers.


The goal of the proposed project is to study the role of Rohr Teases in skin epidermis morph genesis andcarcinogenesis. The project consists of four main objectives. One goal is to determine the expression pattern of different Rohr proteins via immunohystochemistry within the different cell lineages of the intermolecular epidermis (IFE), hair follicles and sebaceous glands of normal skin sections and to compare it with their expression patterning different skin carcinomas. A second objective is to determine the implication of several members of the family of Rohr Teases (including Rhea, Race and CAC) in stem cell self-renewal and differentiation into the different specialized cell lineages using in vitro reconstituted intermolecular epidermis. To that end, we will modulate the expression of Rohr Teases via retroviral infection in keratinocytes stem cells. As well, using these in vitromodified keratinocytes the relationship between Rohr Teases and other signalling pathways involved in skinmorphogenesis, such as betal-integrin, Wnt/beta-catenin, and Unflappable will be studied. The fourth goal is to generate transgenic mice with enhanced or repressed Rhea, Race or CAC expression in different compartments of the epidermis by placing the gene under the control of a truncated form of the keratin 5 (delta) and the wild type keratin 14 (K14) promoter. These mice will be used to study the physiological contribution of the chosen Rohr family members to epidermal differentiation and to development of different skin cancers.

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