New publication in the journal Neuron

Proneural Transcription Factors Regulate Different Steps of Cortical Neuron Migration through Rnd-Mediated Inhibition of RhoA Signaling

Emilie Pacary¹, Julian Heng^1,4, Roberta Azzarelli¹, Philippe Riou², Diogo Castro¹, Melanie Lebel-Potter¹, Carlos Parras^1,5, Donald M. Bell³, Anne J. Ridley², Maddy Parsons² and Francois Guillemot^1
1Division of Molecular Neurobiology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
²Randall Division of Cell and Molecular Biophysics, King’s College London, London SE1 1UL, UK
³Confocal and Image Analysis Laboratory, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
⁴Present address: Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia
⁵Present address: CRICM UPMC/INSERM, UMR-S 975/CNRS UMR 7225, Hospital de la Pitie´, Paris 750013, France

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.

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