The function of e-and p-cadherin in epidermal differentiation

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Project objective

Research objectives and content Various cell adhesion molecules including members of the integrin family and the cadherins have been implicated in normal differentiation processes. The main focus of this research proposal is the analysis of the molecular mechanisms by which E- and P-cadherin control differentiation and spatial organisation of the cells within the epidermis. The epidermis consists of multiple layers of keratinocytes and can be reconstituted in culture providing an ideal experimental model for the analysis of growth, differentiation and morphogenesis in a self renewing tissue. Terminal differentiation of keratinocytes occurs as they move through the suprabasal layers to the skin surface. A specific expression pattern of E- and P-cadherin has been found during this differentiation process: P-cadherin appears predominantly in the basal layer of the epidermis, whereas E-cadherin expression is more restricted to the suprabasal, upper layers. Furthermore, it is known that the cytoplasmic Beta-catenin is a component of the cadherin-adhesion complex and is also involved in the wnt/wingless pathway. Two approaches will be taken: (1) to elucidate the function of E- and P-cadherin during keratinocyte differentiation, recombinant E- and P-cadherin molecules will be designed and tested on their role during differentiation of specific subpopulations of epidermal cells and (2) transgenic mice expressing E-cadherin or P-cadherin in specific epidermal layers will be generated and analysed for abnormal epidermal differentiation. Training content (objective, benefit and expected impact) The proposed experiments will determine the function of cell adhesion molecules E- and P-cadherin during the growth and differentiation of epidermal cells. Furthermore, the role of the cytoplasmic protein Beta-catenin in this process (adhesion or signalling function) will be analized. The understanding of the molecular basis of epidermal differentiation represents a key element for the further comprehension of biological processes involved in tumor progression. Links with industry / industrial relevance (22)

Original text from CORDIS.

Participants

• Imperial Cancer Research Fund · LondonCoordinatorUnited Kingdom
• Not availableCity levelGermany

Links

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