Ezh2 Orchestrates Topographic Migration and Connectivity of Mouse Precerebellar Neurons

被引：96

作者：

Di Meglio, Thomas ^{[1
]}

Kratochwil, Claudius F. ^{[1
,2
]}

Vilain, Nathalie ^{[1
]}

Loche, Alberto ^{[1
,2
]}

Vitobello, Antonio ^{[1
,2
]}

Yonehara, Keisuke ^{[1
]}

Hrycaj, Steven M. ^{[3
]}

Roska, Botond ^{[1
,2
]}

Peters, Antoine H. F. M. ^{[1
,2
]}

Eichmann, Anne ^{[3
,4
]}

Wellik, Deneen ^{[5
]}

Ducret, Sebastien ^{[1
]}

Rijli, Filippo M. ^{[1
,2
]}

机构：

[1] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland

[2] Univ Basel, CH-4056 Basel, Switzerland

[3] Yale Univ, Sch Med, Dept Internal Med, Yale Cardiovasc Res Ctr, New Haven, CT 06511 USA

[4] INSERM, CIRB, U1050, F-75005 Paris, France

[5] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA

来源：

SCIENCE | 2013年 / 339卷 / 6116期

基金：

瑞士国家科学基金会;

关键词：

GUIDANCE; COMPLEX;

D O I：

10.1126/science.1229326

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：204 / 207

页数：4

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