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Rôle et importance des contrôles post-transcriptionnels de l'expression génétique dans la segmentation somitique des vertébrés – SEGPOSREG

Submission summary

In vertebrate embryos, a part of mesodermal derivatives is composed of somites.Somitic cells will evolve in adults in skeletal muscles, bones and derm. Somites are organised in a segmented manner, as they are present as a series of repetitive, quasi-identical, metameric units along the embryonic antero-posterior axis. Somitic segmentation takes place during the rostro-caudal elongation of the embryo. It relies on the cyclical expression of a number of mRNA in the presomitic mesoderm, with transitory bursts of expression every one to two hours. Although the expression pattern of these mRNAs makes it obvious that they are very unstable, the molecular mechanisms leading to their rapid degradation remain obscure. Nevertheless, mRNA degradation is most often triggered by the specific binding of one or several RNA-binding protein(s). We propose to identify and analyse the in vivo functions of post-transcriptional controls of gene expression, including controls of mRNA stability, that are required for vertebrate somitic segmentation. - The project is divided into four successive steps: - (1), The identification of the RNA-binding proteins, known to play a role in the control of mRNA stability, that are expressed in the presomitic mesoderm of Xenopus and mouse embryos, and as such potentially play a role in somitic segmentation. - (2), The analysis, by loss-of-functions experiments, of the requirement of each of these RNAbinding proteins for somitic segmentation. This will be done, in Xenopus, by morpholino antisense oligonucleotide-mediated knock-down experiments, and, in mouse, by using genetically engineered mice disrupted for the genes encoding the considered RNA-binding proteins. In these animals, somitic segmentation will be analysed by several approaches. - (3), The identification, on a systematic basis, of the mRNA targets of the RNA-binding proteins required for somitic segmentation. This will be done by immunoprecipitating RNA-binding proteins and identifying the co-immunoprecipitated mRNAs by a microarray approach, or a massively parallel sequencing approach. - (4), The analysis of the causal relationships between the segmentation defects and the mRNA targets. The interaction between the RNA-binding proteins and their most pertinent mRNA targets will be inhibited, and the consequences on somitic segmentation will be analysed. - Together, these experiments will provide definitive data on the mechanisms controlling somitic segmentation in vertebrates. - ...

Project coordination

Luc PAILLARD (Université)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Help of the ANR 200,000 euros
Beginning and duration of the scientific project: - 48 Months

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