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GENES & DEVELOPMENT 21:2347-2357, 2007
©2007 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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N-cofilin is associated with neuronal migration disorders and cell cycle control in the cerebral cortex

Gian Carlo Bellenchi1,2,4, Christine B. Gurniak1,4, Emerald Perlas1, Silvia Middei3, Martine Ammassari-Teule3, and Walter Witke1,5

1 Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), 00015 Monterotondo, Italy; 2 Department of Cell Biology and Neuroscience, Instituto Superiore di Sanità, 00161 Rome, Italy; 3 Consiglio Nazionale delle Ricerche (CNR) Institute for Neuroscience, Santa Lucia Foundation, 00143 Rome, Italy

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.

[Keywords: Cortex development; cofilins; actin cytoskeleton; neuronal migration disorders; cell cycle]

Received March 22, 2007; revised version accepted July 27, 2007.

4 These authors contributed equally to this work.

5 Corresponding author.

E-MAIL witke@embl-monterotondo.it; FAX 0039-06-90091-272.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.434307


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