title: Robo4 regulates the radial migration of newborn neurons in developing neocortex.
abstract: 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.
authors: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Wang
authors: W
authors: Zheng
authors: An-qi
authors: AQ
authors: Geng
authors: Peng-fei
authors: PF
authors: Li
authors: Yi
authors: Y
authors: Wang
authors: Xiao-bing
authors: XB
authors: Yuan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000235:genetics* / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000254:growth & development; D018274:Electroporation; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000502:physiology; D019579:Neocortex / Q000166:cytology* / Q000254:growth & development*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D000097905:Roundabout Proteins
chemical_list: D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C540792:Robo4 protein, mouse; C578845:Robo4 protein, rat; D000097905:Roundabout Proteins