title: Proneural transcription factors regulate different steps of cortical neuron migration through Rnd-mediated inhibition of RhoA signaling.
abstract: Little is known of the intracellular machinery that controls the motility of newborn neurons. We have previously shown that the proneural protein Neurog2 promotes the migration of nascent cortical neurons by inducing the expression of the atypical Rho GTPase Rnd2. Here, we show that another proneural factor, Ascl1, promotes neuronal migration in the cortex through direct regulation of a second Rnd family member, Rnd3. Both Rnd2 and Rnd3 promote neuronal migration by inhibiting RhoA signaling, but they control distinct steps of the migratory process, multipolar to bipolar transition in the intermediate zone and locomotion in the cortical plate, respectively. Interestingly, these divergent functions directly result from the distinct subcellular distributions of the two Rnd proteins. Because Rnd proteins also regulate progenitor divisions and neurite outgrowth, we propose that proneural factors, through spatiotemporal regulation of Rnd proteins, integrate the process of neuronal migration with other events in the neurogenic program.
authors: Division of Molecular Neurobiology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
authors: Emilie
authors: E
authors: Pacary
authors: Julian
authors: J
authors: Heng
authors: Roberta
authors: R
authors: Azzarelli
authors: Philippe
authors: P
authors: Riou
authors: Diogo
authors: D
authors: Castro
authors: Mélanie
authors: M
authors: Lebel-Potter
authors: Carlos
authors: C
authors: Parras
authors: Donald M
authors: DM
authors: Bell
authors: Anne J
authors: AJ
authors: Ridley
authors: Maddy
authors: M
authors: Parsons
authors: François
authors: F
authors: Guillemot
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015153:Blotting, Western; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; C499317:Ascl1 protein, mouse; C513341:Rnd3 protein, mouse