A first step to regenerative medicine is to find a means to cause controlled de-differentiation of adult tissue. Plurigenes aims at achieving major breakthroughs in the discovery and understanding of the function of genes controlling pluripotency in the central nervous system. These later could enable the de-differentiation of terminally differentiated neural cells into pluripotent cells through transgenesis, a goal that fully meets the requirements of LSH-2004-1.1.0-1. Plurigenes will start by identifying candidate genes in model organisms, following original approaches involving screens performed by in situ hybridations on well characterised neural structures or by gain of function analysis. As pointed out in LSH-2004-1.1.0-1 innovative technologies of transgenesis and imaging in several model organisms will be settled to reach this goal. The project will first characterise in vitro and in vivo the functions of candidate genes involved in the maintenance of pluripotency. On selected genes, it will then validate the possibility to restore the pluripotency of terminally differentiated cells through transgenesis of the candidate genes. Finally, Plurigenes will identify molecular partners and related pathways associated with pluripotency. The project will result in the identification of evolutionarily conserved genes associated with cellular pluripotency; improved methods for transgenesis in fish and ascidians and innovative methods for cell imaging and finally, protocols for the de-differentiation of neural cells.
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