Bacurd2 is a novel interacting partner to Rnd2 which controls distinct phases of radial migration within the developing mammalian cerebral cortex

Within the developing mammalian cerebral cortex, newborn excitatory neurons engage in radial migra9on as they leave their birthplace in the germinal ventricular zone and reach their final loca9on before undergoing terminal differen9a9on. We have previously reported that the atypical RhoA GTPase Rnd2 promotes the radial migra9on of newborn cor9cal projec9on neurons within the embryonic cerebral cortex (REF), but its downstream signalling pathways are not well understood. In this study, we iden9fy Bacurd2 (a member of the BTB-domain containing adaptor for Cul3- mediated RhoA degrada9on) as a novel interac9ng partner to Rnd2 which promotes radial migra9on within the mouse cerebral cortex during embryonic and post-natal development. We find that Bacurd2 binds Rnd2 at its C-terminus, and this interac9on is cri9cal to its role in cell migra9on. To inves9gate how the interac9on between Bacurd2 and Rnd2 might be important for cell migra9on within the embryonic cortex, we engineered a Bacurd2:Rnd2 chimeric construct and discovered that the migra9on- defect of Rnd2shRNA-treated cells could be corrected by co-delivery of this construct. Our cellular analysis further reveals that Bacurd2-Rnd2 signalling is cri9cal for coordina9ng the mul9polar-to-bipolar transi9on of neurons within the intermediate zone, as well as their radial migra9on within the cor9cal plate. Therefore, our results iden9fy Bacurd2 as a cri9cal player during cerebral cor9cal development which guides the proper posi9oning of newborn neurons through its interac9on with Rnd2.