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N-丝切蛋白与大脑皮质中的神经元迁移障碍及细胞周期调控有关。

N-cofilin is associated with neuronal migration disorders and cell cycle control in the cerebral cortex.

作者信息

Bellenchi Gian Carlo, Gurniak Christine B, Perlas Emerald, Middei Silvia, Ammassari-Teule Martine, Witke Walter

机构信息

Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), 00015, Monterotondo, Italy.

出版信息

Genes Dev. 2007 Sep 15;21(18):2347-57. doi: 10.1101/gad.434307.

Abstract

Many neuronal disorders such as lissencephaly, epilepsy, and schizophrenia are caused by the abnormal migration of neurons in the developing brain. The role of the actin cytoskeleton in neuronal migration disorders has in large part remained elusive. Here we show that the F-actin depolymerizing factor n-cofilin controls cell migration and cell cycle progression in the cerebral cortex. Loss of n-cofilin impairs radial migration, resulting in the lack of intermediate cortical layers. Neuronal progenitors in the ventricular zone show increased cell cycle exit and exaggerated neuronal differentiation, leading to the depletion of the neuronal progenitor pool. These results demonstrate that mutations affecting regulators of the actin cytoskeleton contribute to the pathology of cortex development.

摘要

许多神经元疾病,如无脑回畸形、癫痫和精神分裂症,是由发育中的大脑中神经元的异常迁移引起的。肌动蛋白细胞骨架在神经元迁移障碍中的作用在很大程度上仍然不清楚。在这里,我们表明F-肌动蛋白解聚因子n-丝切蛋白控制大脑皮质中的细胞迁移和细胞周期进程。n-丝切蛋白的缺失会损害放射状迁移,导致中间皮质层缺失。脑室区的神经元祖细胞显示出增加的细胞周期退出和过度的神经元分化,导致神经元祖细胞池的耗竭。这些结果表明,影响肌动蛋白细胞骨架调节因子的突变导致了皮质发育的病理学变化。

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