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GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation.

Morgan-Smith M, Wu Y, Zhu X, Pringle J, Snider WD - Elife (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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No apparent migration defect in Gsk3:Dlx5/6 mice.P0 quantification of Ai3-positive neurons in control and Gsk3-deleted interneurons using 8 bin analysis spanning white matter to the dorsal stream. p-values reaching significance are shown in figure, unpaired t-test. (n = 2 controls, 3894 total cux1 neurons, n = 2 cko, 3681 total cux1 neurons).DOI:http://dx.doi.org/10.7554/eLife.02663.008
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fig3s1: No apparent migration defect in Gsk3:Dlx5/6 mice.P0 quantification of Ai3-positive neurons in control and Gsk3-deleted interneurons using 8 bin analysis spanning white matter to the dorsal stream. p-values reaching significance are shown in figure, unpaired t-test. (n = 2 controls, 3894 total cux1 neurons, n = 2 cko, 3681 total cux1 neurons).DOI:http://dx.doi.org/10.7554/eLife.02663.008

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.


GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation.

Morgan-Smith M, Wu Y, Zhu X, Pringle J, Snider WD - Elife (2014)

No apparent migration defect in Gsk3:Dlx5/6 mice.P0 quantification of Ai3-positive neurons in control and Gsk3-deleted interneurons using 8 bin analysis spanning white matter to the dorsal stream. p-values reaching significance are shown in figure, unpaired t-test. (n = 2 controls, 3894 total cux1 neurons, n = 2 cko, 3681 total cux1 neurons).DOI:http://dx.doi.org/10.7554/eLife.02663.008
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109311&req=5

fig3s1: No apparent migration defect in Gsk3:Dlx5/6 mice.P0 quantification of Ai3-positive neurons in control and Gsk3-deleted interneurons using 8 bin analysis spanning white matter to the dorsal stream. p-values reaching significance are shown in figure, unpaired t-test. (n = 2 controls, 3894 total cux1 neurons, n = 2 cko, 3681 total cux1 neurons).DOI:http://dx.doi.org/10.7554/eLife.02663.008
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.

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.

View Article: PubMed Central - PubMed

Affiliation: 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.

Show MeSH
Related in: MedlinePlus