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

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 fact...

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Published inGenes & development Vol. 21; no. 18; pp. 2347 - 2357
Main Authors Bellenchi, Gian Carlo, Gurniak, Christine B, Perlas, Emerald, Middei, Silvia, Ammassari-Teule, Martine, Witke, Walter
Format Journal Article
LanguageEnglish
Published United States Cold Spring Harbor Laboratory Press 15.09.2007
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Summary: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.
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These authors contributed equally to this work.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.434307