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

Abstract :


Neurons in the embryonic mammalian brain are generated in progenitor zones which line the ventricles.
Soon after their birth, they undergo active cell migration to reach distant locations, where they eventually form neuronal circuits. Although migration is a fundamental behavior of neurons, little is known of the intracellular machinery that controls the motility of newborn neurons.
Recent studies have shown that Neurogenin2/Neurog2 and Mash1, two proneural transcription factors with a prominent role in neurogenesis in the embryonic cortex (Nieto et al., 2001; Schuurmans et al., 2004), also regulate neuronal migration (Hand et al., 2005; Ge et al., 2006).
Here we show, by combining RNA interference and in utero electroporation, that these two proneural proteins activate distinct pathways in migrating cortical neurons. Neurog2 and Mash1 induce the expression of the atypical Rho GTPases, Rnd2 and Rnd3, respectively, in migrating neurons of the embryonic cerebral cortex. By FRET, we demonstrate that the two Rnd proteins inhibit RhoA activity in different compartments of the neuron and thereby control different phases of the migratory process: multipolar to bipolar transition in the intermediate zone for Rnd2 and locomotion in the cortical plate for Rnd3.
Together, our results demonstrate that proneural factors, through spatio-temporal regulation of different Rnd proteins, integrate the process of neuronal migration with other events in the neurogenic programme. Moreover our data reveal that the different steps of neuronal migration in the cerebral cortex are under independent transcriptional control.

Selected publications

Pacary E, Heng J, Azzarelli R, Riou P, Castro D, Lebel-Potter M, Parras C, Bell DM, Ridley AJ, Parsons M, Guillemot F. Proneural transcription factors regulate different steps of cortical neuron migration through Rnd-mediated inhibition of RhoA signaling. Neuron (in press).
Marteau L., Pacary E, Valable S, Bernaudin M, Guillemot F, Petit E. Angiopoietin-2 regulates cortical neurogenesis in the developing telencephalon. Cereb Cortex 2010 Dec 2. [Epub ahead of print]).

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