Résumé :
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Communication n° 721. We still have a rather primitive understanding of the molecular mechanisms that underlie vertebrate sensory-motor system establishment, physiology and physiopathology. Although a series of novel techniques have been developed over the last 10 years, it is still difficult to identify new genes that play important roles during vertebrate nervous system development and physiology. The goal of this project is to use the fruit fly Drosophila melanogaster as a tool to probe the role of vertebrate genes expressed in the nervous system but of unknown function. Because the majority of genes playing important roles in the Drosophila nervous system, when isolated and analyzed, play similar if not identical roles in vertebrates, we envision that the information gained from this Drosophila project will allow us to design focused strategies to better approach the function of the corresponding orthologue genes in vertebrate systems. The candidate genes are pre-selected from a screen for their restricted expression pattern in sub-populations of mouse DRG (Dorsal Root Ganglia) neurons, in particular in proprioceptive neurons innervating the muscle. We are in the process of establishing a large molecular description of the expression pattern of hundreds of genes in the mouse DRG, at different stages (embryonic, postnatal, and adult) and under different conditions (normal, and within different animals models such as axotomy or knockout mice). This detailed analysis did already allow us to select some pertinent candidates that are currently subject to in-depth functional analysis in Drosophila and vertebrate. To date, we have collected and created genetic tools allowing for functional analysis of many of the candidates, obtained important information regarding the molecular function of two of them in Drosophila (Acj6 and Zfh1) and have started to explore the activities of the corresponding mouse orthologue (Brn3C and Zfhx1a). Primary results concerning the function of these in the establishment and physiology of the sensory-motor system in Drosophila and in the mouse will be presented.
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