Abstract
SummaryLittle 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.
Highlights
Neurons in the embryonic mammalian brain are generated in progenitor zones that line the ventricles
Because Rnd proteins 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
Another proneural factor present in the embryonic cortex, Ascl1 (Britz et al, 2006) has been shown to promote neuronal migration when overexpressed in cortical progenitors (Ge et al, 2006), it is unclear whether this activity reflects a genuine role in cortical neuron migration and the downstream mechanisms involved are unknown
Summary
Neurons in the embryonic mammalian brain are generated in progenitor zones that line the ventricles. Recent studies have shown that Neurogenin ( known as Neurog2), a proneural factor with a prominent role in neurogenesis in the embryonic cortex (Nieto et al, 2001; Schuurmans et al, 2004), promotes migration in the cortex through direct induction of the expression of the small GTPase Rnd and possibly other genes involved in regulating the cytoskeleton, including RhoA, doublecortin, and p35 (Ge et al, 2006; Hand et al, 2005; Heng et al, 2008). Another proneural factor present in the embryonic cortex, Ascl (Britz et al, 2006) has been shown to promote neuronal migration when overexpressed in cortical progenitors (Ge et al, 2006), it is unclear whether this activity reflects a genuine role in cortical neuron migration and the downstream mechanisms involved are unknown
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