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Publication : Robo4 regulates the radial migration of newborn neurons in developing neocortex.

First Author  Zheng W Year  2012
Journal  Cereb Cortex Volume  22
Issue  11 Pages  2587-601
PubMed ID  22123939 Mgi Jnum  J:202213
Mgi Id  MGI:5517661 Doi  10.1093/cercor/bhr330
Citation  Zheng W, et al. (2012) Robo4 regulates the radial migration of newborn neurons in developing neocortex. Cereb Cortex 22(11):2587-601
abstractText  During the morphogenesis of neocortex, newborn neurons undergo radial migration from the ventricular zone toward the surface of the cortical plate to form an "inside-out" lamina structure. The spatiotemporal signals that control this stereotyped radial migration remain elusive. Here, we report that a recently identified Robo family member Robo4 (Magic Roundabout), which was considered to be solely expressed in endothelial cells, is expressed in developing brain and regulates the radial migration of newborn neurons in neocortex. Downregulation of Robo4 expression in cortical newborn neurons by using in utero electroporation, with either specific siRNAs in wild-type rodents or with Cre recombinase in floxed-robo4 mutant mice, led to severe defects in the radial migration of newborn neurons with misorientation of these neurons. Moreover, newborn neurons transfected with Robo4 siRNAs exhibited significantly lower motility in a transwell migration assay (Boyden chamber) in the absence of Slit and significantly higher sensitivity to the repulsive effect of Slit in both transwell migration assay and growth cone collapse assay. Overall, our results showed an important role of Robo4 in the regulation of cortical radial migration through Slit-dependent and -independent mechanisms.
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