| Literature DB >> 23307742 |
Thomas Di Meglio1, Claudius F Kratochwil, Nathalie Vilain, Alberto Loche, Antonio Vitobello, Keisuke Yonehara, Steven M Hrycaj, Botond Roska, Antoine H F M Peters, Anne Eichmann, Deneen Wellik, Sebastien Ducret, Filippo M Rijli.
Abstract
We investigated the role of histone methyltransferase Ezh2 in tangential migration of mouse precerebellar pontine nuclei, the main relay between neocortex and cerebellum. By counteracting the sonic hedgehog pathway, Ezh2 represses Netrin1 in dorsal hindbrain, which allows normal pontine neuron migration. In Ezh2 mutants, ectopic Netrin1 derepression results in abnormal migration and supernumerary nuclei integrating in brain circuitry. Moreover, intrinsic topographic organization of pontine nuclei according to rostrocaudal progenitor origin is maintained throughout migration and correlates with patterned cortical input. Ezh2 maintains spatially restricted Hox expression, which, in turn, regulates differential expression of the repulsive receptor Unc5b in migrating neurons; together, they generate subsets with distinct responsiveness to environmental Netrin1. Thus, Ezh2-dependent epigenetic regulation of intrinsic and extrinsic transcriptional programs controls topographic neuronal guidance and connectivity in the cortico-ponto-cerebellar pathway.Entities:
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Year: 2013 PMID： 23307742 PMCID： PMC4824054 DOI： 10.1126/science.1229326
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728