期刊
SCIENCE
卷 339, 期 6116, 页码 204-207出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1229326
关键词
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资金
- European Molecular Biology Organization Long-Term Fellowship
- Swiss National Science Foundation [Sinergia CRSI33_127440]
- Association pour la Recherche sur la Sclerose en Plaques
- Novartis Research Foundation
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.
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