Roles of Rho small GTPases in the tangentially migrating neurons

Abstract

Rho small GTPases are members of the Ras superfamily of monomeric 20~30 kDa GTP-binding proteins. These proteins function as molecular switches that regulate various cellular processes such as migration, adhesion and proliferation. Cycling between GDP-bound inactive and GTP-bound active forms is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and GDPdissociation inhibitors (GDIs). Among 20 different mammalian Rho GTPases identified to date, RhoA, Rac1 and Cdc42 have been most extensively investigated; regulation of migration, adhesion and proliferation by these proteins have been well documented in a variety of cell types, including neurons. In neurons, RhoA, Rac1 and Cdc42 are crucial for axon guidance, dendrite formation and spine morphogenesis, where molecular machineries required for cell migration and adhesion play essential roles. Recently, accumulating experimental data indicate the participation of Rho GTPases in neuronal cell migration. To establish the cortical lamination and synapse network formation, highly specialized modes of neuron migration are essential, which include 1) radial migration of excitatory pyramidal neurons along radial glial fibers, 2) tangential migration of GABAergic cortical (inhibitory) interneurons along emerging axon tracts and 3) chain migration of interneurons ensheathed in a glial network, which is observed only in olfactory bulb-directed adult neurogenesis. While roles of Rho GTPases in the radial migration have been well reviewed, knowledge of their functions in tangential migration and chain migration are fragmentary to date. In this review, we focus on the roles of Rho small GTPases and their related molecules in tangential migration, together with the possible application of the electroporation method to analyses for this mode of migration in embryonic and postnatal mouse brain.