Drosophila melanogaster as a model to study the role of the Fragile X Mental Retardation Protein in the genome stability pathway mediated by piRNAs

Fragile-X syndrome represents, together with the Down syndrome, the most common form of mental retardation in humans. It affects 1/4000 males and 1/6000-8000 females. Beyond the mental retardation, in Fragile-X patients, defects in the germline tissues, in particular in testes, are present. Many studies have demonstrated that the fruitfly, Drosophila melanogaster, is a good experimental model to understand the molecular process, causing this disease. The Drosophila genome bears a single fragile-X related gene, the dFMR1 gene. The main goal of the proposed project is to define in detail the molecular role of dFMR1 in Drosophila melanogaster gonads, in particular to define its role in the mechanisms regulating the mobile genetic elements or transposable elements, that could cause genome instability, at the basis of diverse human diseases, and to gain new insights in all the molecular mechanisms in which dFMR1 is involved even in the nervous system. The project's idea originates from our preliminary data that indicate the dFMR1 involvement in the piRNA-mediated silencing of the transposable elements, operating both in Drosophila melanogaster gonads and in the nervous system and that are conserved during evolution. This project will give a real contribute to the comprehension of the molecular role of the dFMR1 gene product in the gonads and in the nervous system. All the new results coming from this research project could be transferred and analyzed in humans.