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靶向CoREST的微小RNA控制迁移中皮质神经元的极化。

MicroRNA targeting of CoREST controls polarization of migrating cortical neurons.

作者信息

Volvert Marie-Laure, Prévot Pierre-Paul, Close Pierre, Laguesse Sophie, Pirotte Sophie, Hemphill James, Rogister Florence, Kruzy Nathalie, Sacheli Rosalie, Moonen Gustave, Deiters Alexander, Merkenschlager Matthias, Chariot Alain, Malgrange Brigitte, Godin Juliette D, Nguyen Laurent

机构信息

GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.

GIGA-Signal Transduction, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.

出版信息

Cell Rep. 2014 May 22;7(4):1168-83. doi: 10.1016/j.celrep.2014.03.075. Epub 2014 May 1.

DOI:10.1016/j.celrep.2014.03.075
PMID:24794437
Abstract

The migration of cortical projection neurons is a multistep process characterized by dynamic cell shape remodeling. The molecular basis of these changes remains elusive, and the present work describes how microRNAs (miRNAs) control neuronal polarization during radial migration. We show that miR-22 and miR-124 are expressed in the cortical wall where they target components of the CoREST/REST transcriptional repressor complex, thereby regulating doublecortin transcription in migrating neurons. This molecular pathway underlies radial migration by promoting dynamic multipolar-bipolar cell conversion at early phases of migration, and later stabilization of cell polarity to support locomotion on radial glia fibers. Thus, our work emphasizes key roles of some miRNAs that control radial migration during cerebral corticogenesis.

摘要

皮层投射神经元的迁移是一个多步骤过程,其特征是动态的细胞形态重塑。这些变化的分子基础仍然难以捉摸,而目前的研究描述了微小RNA(miRNA)如何在放射状迁移过程中控制神经元极化。我们发现miR-22和miR-124在皮层壁中表达,它们靶向CoREST/REST转录抑制复合物的成分,从而调节迁移神经元中的双皮质素转录。这一分子途径通过在迁移早期促进动态的多极-双极细胞转换以及随后稳定细胞极性以支持在放射状胶质纤维上的移动,为放射状迁移奠定了基础。因此,我们的研究强调了一些miRNA在大脑皮质发生过程中控制放射状迁移的关键作用。

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