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

被引:155
作者
Bellenchi, Gian Carlo
Gurniak, Christine B.
Perlas, Emerald
Middei, Silvia
Ammassari-Teule, Martine
Witke, Walter [1 ]
机构
[1] European Mol Biol Lab, Mouse Biol Unit, I-00015 Monterotondo, Italy
[2] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy
[3] CNR, Inst Neurosci, Santa Lucia Fdn, I-00143 Rome, Italy
关键词
cortex development; cofilins; actin cytoskeleton; neuronal migration disorders; cell cycle;
D O I
10.1101/gad.434307
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:2347 / 2357
页数:11
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