In vivo functions of small GTPases in neocortical development

The complex mammalian cortex develops from a simple neuroepithelium through the proliferation of neuronal progenitors, their asymmetric division and cell migration. Newly generated neurons transiently assume a multipolar morphology before they polarize to form a trailing axon and a leading process that is required for their radial migration. The polarization and migration events during cortical development are under the control of multiple signaling cascades that coordinate the different cellular processes involved in neuronal differentiation. GTPases perform essential functions at different stages of neuronal development as central components of these pathways. They have been widely studied using cell lines and primary neuronal cultures but their physiological function in vivo still remains to be explored in many cases. Here we review the function of GTPases that have been studied genetically by the analysis of the embryonic nervous system in knockout mice. The phenotype of these mutants has highlighted the importance of GTPases for different steps of development by orchestrating cytoskeletal rearrangements and neuronal polarization.