microRNAs and Neurogenesis Control
Start date: Jul 1, 2009,
End date: Feb 28, 2010
Vertebrate brain development and function require the life-long regulation of neural stem cell maintenance and neuronal production. Recent evidence, in part obtained in the host laboratory, suggest that the microRNA miR-9 might be an important regulator of neurogenesis, by driving neural progenitors towards differentiation. Notably, injection of a miR-9 morpholino antisense oligonucleotide into zebrafish embryos decreases neuronal differentiation in the embryonic hindbrain. The spatio-temporal expression pattern of miR-9 is suggestive of a neuronal subtype-specific action. The researcher will thus characterize more precisely the neuronal deficit of miR-9 morphant embryos, using markers of different neuronal populations. To understand the mechanisms underlying miR-9 function, the interaction between miR-9 and selected in silico predicted targets will be tested, and an innovative microarray-based biochemical approach for identifying targets in vivo will be developped. The NEuromiR project also includes epistasis experiments to connect miR-9 action with that of other neurogenesis regulators (Rest, Her) expressed in progenitors. Finally, in a longer term and to extend the findings to later developmental stages and adulthood, zebrafish transgenic lines that enable to conditionally enhance or deplete miR-9 function will be engineered. Together, this project will shed light onto the fine-tuning of neurogenesis control by microRNAs.
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