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

Roberta Azzarelli, Emilie Pacary, Ritu Garg, Patricia Garcez, Debbie van den Berg, Philippe Riou, Anne J Ridley, Roland H Friedel, Maddy Parsons, François Guillemot

Research output: Contribution to journalArticle (Academic Journal)peer-review

46 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3405
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 27 Feb 2014

Keywords

  • Animals
  • Blotting, Western
  • COS Cells
  • Cell Line, Tumor
  • Cell Movement
  • Cercopithecus aethiops
  • Cerebral Cortex
  • Fluorescence Resonance Energy Transfer
  • In Situ Hybridization
  • Mice
  • Microscopy, Confocal
  • Nerve Tissue Proteins
  • Neurons
  • Protein Binding
  • RNA Interference
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein
  • Journal Article
  • Research Support, Non-U.S. Gov't

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