Développement précoce du système nerveux [Early development of the nervous system]
Un des axes principaux de recherche du laboratoire est l'étude des étapes précoces de la formation du système nerveux des vertébrés. Nous nous intéressons en particulier à des facteurs de transcription (Hairy, DMRT, IA-1,...) exprimés précocément et de manière régionalisée dans le système nerveux en formation. La fonction de ces gènes est étudiée via des approches de sur- et sous-expression dans l'embryon de xénope et par l'analyse du phénotype de souris mutantes où ces gènes ont été invalidés. [Our current research projects consists of three parts: 1. Role of the RNA-binding protein XSeb4R in ectoderm formation We recently provided evidence that the RRM-type RNA binding protein XSeb4R, originaly identified as a proneural factor in retinogenesis, acts at the vegetal pole of the blastula embryo as a post-transcriptional regulator of VegT and as such is required for endoderm specification and mesoderm induction. However, maternal XSeb4R transcripts are found uniformely distributed at blastula stage throughout the embryo, suggesting that it might also play a role in ectodermal progenitor specification. We are currently investigating this possibility (through gain and loss of function experiments in the frog). 2. Role of the Prdm transcription factor family in mouse spinal cord neurogenesis Prdm genes encode transcriptional regulators containing a N-terminal SET domain functioning in chromating mediated transcriptional repression, followed by a variable number of zinc finger repeats. Several studies, including our recent work on one family member, Evi-1/prdm3, have shown that some of these genes are essential for embryonic development. We recently discovered that multiple genes of the prdm family are expressed in the developing Xenopus CNS in a spatially and temporally restricted manner and are currently investigating their function in spinal cord neurogenesis (through injection experiments in the frog and overexpression and knockdown experiments in the chick embryo by electroporation). 3. Role of the DMRT5 transcription in the development of the cerebral cortex Vertebrate DM domain genes encode a group of zinc finger transcription factors related to the Drosophila doublesex and Caenhorhabditis elegans mab-3 transcription factors whose function in sexual development is well known. We found that one member of this family, DMRT5, is highly expressed during embryogenesis in the developing forebrain and that its expression in the cortex is restricted to progenitors throughout the neurogenic period. We are currently analysing its biological function (by the analysis of knockout mice and gene overexpression and knockdown in utero). ]