Getting to the Right Place

Science Signaling  09 Sep 2008:
Vol. 1, Issue 36, pp. ec317
DOI: 10.1126/scisignal.136ec317

The protein neurogenin 2 not only regulates embryonic neurogenesis in the cortex but also promotes the radial migration of cortical neurons. Heng et al. screened the dorsal telencephalon of embryonic mice for genes whose expression showed reciprocal changes in Neurog2 loss- or gain-of-function embryos and found that expression of the gene encoding the small GTP-binding protein Rnd2 decreased in Neurog2-mutant embryos and increased with Neurog2 overexpression. Rnd2 knockdown through electroporation of siRNA inhibited the radial migration of cortical neurons and elicited abnormal neuronal morphology without affecting the proliferation of neural progenitors or their specification to a neuronal fate. Transient expression of Rnd2 in newborn cortical neurons rescued a defect in migration to the cortical plate elicited by the conditional knockout of Neurog2 in embryonic brain (which led to the loss of Rnd2 expression), although these neurons failed to complete migration to the upper layer of the cortical plate. The authors identified a 366-bp sequence 3′ to the Rnd2 gene that contained two Neurog2 consensus binding sites. Chromatin immunoprecipitation (ChIP) analysis revealed that Neurog2 bound to this sequence (which the authors called the Rnd2 3′ enhancer) in cortical cells in vivo and transcriptionally activated a luciferase reporter gene containing the Rnd2 3′ enhancer. Moreover, the Rnd2 3′ enhancer drove expression of a reporter in a pattern that resembled that of endogenous Rnd2 transcripts in the embryonic cortex of transgenic mice. Thus, the authors conclude that Neurog2 regulates radial migration of cortical neurons through the direct transcriptional activation of Rnd2.

J. I.-T. Heng, L. Nguyen, D. S. Castro, C. Zimmer, H. Wildner, O. Armant, D. Skowronska-Krawczyk, F. Bedogni, J.-M. Matter, R. Hevner, F. Guillemot, Neurogenin 2 controls cortical neuron migration through regulation of Rnd2. Nature 455, 114-118 (2008). [PubMed]