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microRNAs and Neurogenesis Control

Final Report Summary - NEUROMIR (microRNAs and Neurogenesis Control)

MicroRNAs are small RNA molecules which have emerged as novel and widespread regulators of gene expression in the past decade. They are currently estimated to comprise 1 % of animal genes, making them one of the largest classes of genetic regulators. The microRNA machinery as a whole has been shown to influence many cellular and developmental processes and each microRNA potentially regulates hundreds of target genes. It therefore appears likely that microRNAs will prove to be crucial regulators of vertebrate development and physiology. It is therefore now important to identify their specific functions. Abnormal expression of microRNAs has been detected in different cancers and may contribute to their formation and to stem cell-related disorders. This makes understanding microRNA function particularly relevant to the study and cure of human diseases.

Interestingly, numerous microRNAs are expressed in a temporally and spatially restricted manner in the developing vertebrate central nervous system. However, so far only a few of them have been subjected to functional analysis, mostly by using in vitro culture systems. The NeuromiR project aimed to better understand the role of these molecules during the formation of the vertebrate central nervous system. As a model system we use the zebrafish embryo, which allows rapid and detailed in vivo analyses of microRNA function. We uncovered a crucial implication of a microRNA, miR-9, in balancing the production of neurons during embryonic development and deciphered its precise mechanism of action by identifying its mRNA targets. These advances in decrypting microRNA function are of crucial importance to assess their implication in disease formation and exploit their properties for therapeutic approaches.