CHARACTERIZATION OF RSPONDIN1, A PROTEIN INVOLVED IN SEX DETERMINATION AND SKIN DIFFERENTIATION AND MALIGNANCY

We have recently demonstrated that the protein R-spondin1 is disrupted in a rare genetic disorder characterized by sex reversal - patients with a female chromosome constitution develop as males - associated with thickening of the skin over the palms and soles and predisposition to skin tumours. The project is aimed at the characterization of the function of R-spondin1 during testis and ovary development as well as during skin development and differentiation. To better analyse the role of the protein during sex determination – a process which is difficult to study as it takes place during an early phase of development of the embryo – we will construct animal models of the disease. Skin differentiation will be studied using an in vitro model for skin growth, similar to the one used to produce new skin for autotransplantation in burned patients. This model, established from skin explants of patient’s and donor skin, will be used also to study the interactions between different cell populations (dermal and epidermal cells; diseased and normal) of the skin. Finally, to evaluate the potential for a terapeutical use of R-spondin, we will try to add the normal protein to the affected skin cells obtained from one of the patients.