Proneural transcription factors regulate different steps of cortical neuron migration through Rnd-mediated inhibition of RhoA signaling

Emille Pacary, Julian Heng, Roberta Azzarelli, Phillipe Riou, Diogo Castro, Melanie Lebel-Potter, Carlos Parras, Donald M Bell, Anne J Ridley, Maddy Parsons, Francois Guillemot

Research output: Contribution to journalArticleResearchpeer-review

152 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1069 - 1084
Number of pages16
JournalNeuron
Volume69
Issue number6
DOIs
Publication statusPublished - 2011

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