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N-cofilin is associated with neuronal migration disorders and cell cycle control in the cerebral cortex
Authors:Bellenchi Gian Carlo  Gurniak Christine B  Perlas Emerald  Middei Silvia  Ammassari-Teule Martine  Witke Walter
Affiliation:Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), 00015, Monterotondo, Italy.
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.
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