Objective The major goal of the proposed project is to study the role of vitamin D and Want signalling in skin morphogenesisand homeostasis, and in the alteration of these processes during the development of neoclassic and alopecia. For that purpose we will develop different experiments with keratinocytes and transgenic mice. First we will describe the interplay between vitamin D or some of its non-hypercalcemic analogues and Wntsignaling in different keratinocytes types, isolated from human and mice epidermis. One subpopulation of thesekeratinocytes is stem cells, which are able to regenerate all cell lineages present in the epidermis. We will express a modified vitamin D receptor (VOR), ÿ-catena or Left proteins (Want effectors) in these keratinocytes by retroviral infection. Then we will treat these cells with vitamin D or its analogues and analyse how their capacity to differentiate into the different keratinocyte lineages is modified. We will analyse how these genetically modified cells are able to regenerate an intermolecular epidermis (IFE), and which of them develop alterations during this process. We will study the changes in gene expression profiles promoted by those genetic modifications or by vitamin D treatment, using microarray analysis. In this way, we will be able to isolate new genes whose expression are regulated by every signalling pathway, and will define its implication in epidermal morph genesis invitro. The results obtained with these experiments will permit us to design the appropriate transgenic mice, expressing those proteins involved in vitamin D and Want signalling pathways, which are implicated in skin morphogenesis. We will use epidermal cell type specific keratin promoters to express those proteins into concrete keratinocytepopulations, including stem cells. Then we will study how modifying these proteins alter epidermalmorphogenesis, including the development of tumorigenesis, alpaca, and epidermal cysts. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesbasic medicinephysiologyhomeostasis Keywords Vitamin D Wnt alopecia catenin epidermal morphogenesis keratinocytes ss stem cells tumorigenesis Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Call for proposal FP6-2002-MOBILITY-5 See other projects for this call Funding Scheme EIF - Marie Curie actions-Intra-European Fellowships Coordinator CANCER RESEARCH UK Address Lincoln's inn field 61 London United Kingdom See on map EU contribution € 0,00
