title: GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation.
abstract: GSK-3 is an essential mediator of several signaling pathways that regulate cortical development. We therefore created conditional mouse mutants lacking both GSK-3α and GSK-3β in newly born cortical excitatory neurons. Gsk3-deleted neurons expressing upper layer markers exhibited striking migration failure in all areas of the cortex. Radial migration in hippocampus was similarly affected. In contrast, tangential migration was not grossly impaired after Gsk3 deletion in interneuron precursors. Gsk3-deleted neurons extended axons and developed dendritic arbors. However, the apical dendrite was frequently branched while basal dendrites exhibited abnormal orientation. GSK-3 regulation of migration in neurons was independent of Wnt/β-catenin signaling. Importantly, phosphorylation of the migration mediator, DCX, at ser327, and phosphorylation of the semaphorin signaling mediator, CRMP-2, at Thr514 were markedly decreased. Our data demonstrate that GSK-3 signaling is essential for radial migration and dendritic orientation and suggest that GSK-3 mediates these effects by phosphorylating key microtubule regulatory proteins.DOI: http://dx.doi.org/10.7554/eLife.02663.001.
authors: UNC Neuroscience Center, University of North Carolina, Chapel Hill, United States Neurobiology Curriculum, University of North Carolina, Chapel Hill, United States meghan_morgan@med.unc.edu.
authors: Meghan
authors: http://orcid.org/0000-0001-5122-2330
authors: M
authors: Morgan-Smith
authors: UNC Neuroscience Center, University of North Carolina, Chapel Hill, United States.
authors: Yaohong
authors: Y
authors: Wu
authors: UNC Neuroscience Center, University of North Carolina, Chapel Hill, United States.
authors: Xiaoqin
authors: X
authors: Zhu
authors: UNC Neuroscience Center, University of North Carolina, Chapel Hill, United States.
authors: Julia
authors: J
authors: Pringle
authors: UNC Neuroscience Center, University of North Carolina, Chapel Hill, United States Neurobiology Curriculum, University of North Carolina, Chapel Hill, United States wsnider@med.unc.edu.
authors: William D
authors: WD
authors: Snider
mesh_terms: D000818:Animals; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology*; D003712:Dendrites / Q000378:metabolism*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D017353:Gene Deletion; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000166:cytology; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009479:Neuropeptides / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D013379:Substrate Specificity; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha; D051059:PTEN Phosphohydrolase; D020764:cdc42 GTP-Binding Protein
keywords: GSK-3; cortical development; neuronal migration; neuronal morphology