Abstract :
[en] The cerebral cortex is one of the most complex structures of the organism whose development requires a tight regulation of cellular events. Generation of cortical neurons, i.e. projection neurons and interneurons, relies on the completion of cell proliferation, cell cycle exit, cell migration and neuronal differentiation. Progenitors of projection neuron are born in the germinative zone of the cortex and migrate by successive waves to the cortical plate where they are organized into six neuronal layers. Furthermore, radial migration is divided into successive phases characterized by highly dynamic morphological changes. Cell proliferation or neuronal migration defects happening during cortical development are often associated with neurological disorders characterized by mental retardation, epilepsy or lissencephaly. A better understanding of the mechanisms underlying neuronal generation and neuronal migration could contribute to the elaboration of new strategies for tackling these diseases.In the past few years, the discovery of microRNAs (miRNAs) opened new avenues to understand mechanisms that finely control gene expression. miRNAs are small non coding RNAs that repress gene expression through specific mechanisms. In that way, miRNAs regulate more than sixty percent of genes in the genome and are thus important for the development of different tissues, including the brain.The aim of our work was to characterize miRNAs functions during cortical development and more particularly during neuronal migration. We showed that loss of miRNAs in progenitors of the telencephalon impaired proliferation, differentiation, survival and migration. We also showed that some defects observed upon Dicer ablation resulted from an increased cell death. In addition, we showed that Cajal-Retzius cells formation and migration were altered upon Dicer ablation, and we identified three members of the LIM-homeodomain family that were misregulated upon Dicer deletion. Finally, we showed that miR-22 and miR-124 directly controlled neuronal migration by targeting CoREST/Dcx signaling pathway. In conclusion, we demonstrated that miRNAs were crucial for cortical development.
