An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration

Abstract

A transcriptional programme initiated by the proneural factors Neurog2 and Ascl1 controls successive steps of neurogenesis in the embryonic cerebral cortex. Previous work has shown that proneural factors also confer a migratory behaviour to cortical neurons by inducing the expression of the small GTP-binding proteins such as Rnd2 and Rnd3. However, the directionality of radial migration suggests that migrating neurons also respond to extracellular signal-regulated pathways. Here we show that the Plexin B2 receptor interacts physically and functionally with Rnd3 and stimulates RhoA activity in migrating cortical neurons. Plexin B2 competes with p190RhoGAP for binding to Rnd3, thus blocking the Rnd3-mediated inhibition of RhoA and also recruits RhoGEFs to directly stimulate RhoA activity. Thus, an interaction between the cell-extrinsic Plexin signalling pathway and the cell-intrinsic Ascl1-Rnd3 pathway determines the level of RhoA activity appropriate for cortical neuron migration.

Abstract

The small GTPases Rnd2 and Rnd3 act downstream of proneural factors to control the migrating behaviour of neurons in the mouse embryonic cerebral cortex. Here, Azzarelli et al. show that Rnd3 binding to the semaphorin receptor PlexinB2 fine-tunes the levels of active RhoA required for cortical neuron migration.