GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation.
Bottom Line: Radial migration in hippocampus was similarly affected.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.
Affiliation: UNC Neuroscience Center, University of North Carolina, Chapel Hill, United States Neurobiology Curriculum, University of North Carolina, Chapel Hill, United States firstname.lastname@example.org.Show MeSH
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Mentions: Importantly, the migration defect in the developing cortex is specific to excitatory pyramidal neurons. In order to assess interneurons, we used the Dlx5/6-Cre (Stenman et al., 2003) line to generate conditional mice lacking Gsk3 in GABAergic interneurons. A robust decrease of GSK-3β protein (84%) was observed in E18 MGE lysates from Gsk3:DLX5/6-Cre mice when compared to littermate controls (Figure 3D,E). Interneuron migration was monitored using the AI3 reporter line (Gsk3-Ai3:Dlx). Surprisingly, in both controls and Gsk3 mutants, interneurons exhibited robust migration along the two migratory streams (yellow arrows) from the medial ganglionic eminence (MGE) (Figure 3A–A'). In Gsk3 mutants, as in controls, interneurons entered all areas of the cortical plate by E19.5. Quantification is shown in (Figure 3—figure supplement 1). These results are not meant to imply that migration of interneurons was normal in every respect as we did not assess migration of specific interneuron subsets.10.7554/eLife.02663.007Figure 3.GSK-3 signaling is dispensable for tangential migration, but required for radial hippocampal migration.
Affiliation: UNC Neuroscience Center, University of North Carolina, Chapel Hill, United States Neurobiology Curriculum, University of North Carolina, Chapel Hill, United States email@example.com.