However, genetic inactivations of the murine homologs of genes mutated in human neuronal

migration disorders so far have failed to reproduce these malformations, prompting the suggestion that mutations at other as-yet-unrecognized loci may result in SBH (Bilasy et al., 2009, Croquelois et al., 2009 and Lee et al., 1997). These discrepancies highlight the complexity of human cerebral cortex in comparison to rodents. Not only do migrating neurons have to cover a much longer distance to their final destination, they also need to change radial guides more often due to the increase in pial surface compared to the ventricular surface with additional radial glia (RG) in the outer SVZ (Fietz et al., 2010, Hansen et al., 2010 and Reillo et al., 2010). Thus, migrating neurons in human cerebral cortex SCH772984 clinical trial may require other pathways as they face additional challenges during their journey. Moreover, radial glial cells may need specific pathways, which are yet ill-understood in the mouse model. Indeed, so far only mutation of MEKK4 has been suggested to affect migrating neurons and radial glial cells, causing disruption of the ventricular surface and protrusions

of neuronal ectopia into the ventricle (Sarkisian et al., 2006). Here we set out to examine the role of the small GTPase RhoA for neuronal migration in the developing cerebral cortex, as RhoA had been suggested to play key roles in directed cell migration in various tissues and organs (Govek et al., 2005 and Heasman and Ridley, 2008). By using pharmacological means and dominant-negative or constitutively active constructs, click here several studies suggested that RhoA is crucial for neuronal migration (Besson et al., 2004, Heng et al., 2008, Kholmanskikh et al., 2003, Nguyen et al., 2006 and Pacary et al., 2011). However, the direct role of RhoA in neuronal migration has never been tested in the developing nervous system in vivo. Recently,

conditional deletion of RhoA has revealed insights into its role at early stages of central nervous system (CNS) development Thymidine kinase in the spinal cord and midbrain, highlighting common functions in the maintenance of adherens junction coupling, as previously shown for other members of this family, such as Cdc42 and Rac1 (Cappello et al., 2006, Chen et al., 2009 and Leone et al., 2010), but an opposite role in regulating cell proliferation in spinal cord versus midbrain (Herzog et al., 2011 and Katayama et al., 2011). Moreover, neuronal migration or positioning of neurons was not examined in these mice at later embryonic or postnatal stages. We therefore set out here to delete RhoA in the brain region mostly affected by migrational disorders, namely, the cerebral cortex. In order to determine the role of RhoA in neuronal migration during the development of the cerebral cortex, the Emx1::Cre mouse line driving recombination at early stages selectively in this region (Cappello et al., 2006 and Iwasato et al.