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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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Migration defect apparent by E16 after Gsk3 deletion in cortical excitatory neurons.Coronal cryostat sections at E16. Layer 6 TBR1 neurons populate appropriate layers in control and Gsk3:Neurod6 mutants. Cux-1 (red) expressing neurons, marker for upper layer 2/3 neurons, are mislocalized in Gsk3:Neurod6 mutant coronal sections. L1 staining labels axon tracts.DOI:http://dx.doi.org/10.7554/eLife.02663.004
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fig1s1: Migration defect apparent by E16 after Gsk3 deletion in cortical excitatory neurons.Coronal cryostat sections at E16. Layer 6 TBR1 neurons populate appropriate layers in control and Gsk3:Neurod6 mutants. Cux-1 (red) expressing neurons, marker for upper layer 2/3 neurons, are mislocalized in Gsk3:Neurod6 mutant coronal sections. L1 staining labels axon tracts.DOI:http://dx.doi.org/10.7554/eLife.02663.004

Mentions: To explore neuronal functions of GSK-3, we first assessed cortical lamination at E16, a time of rapid neuronal migration along radial glial processes. Deep layer neurons appeared to be normally positioned (Figure 1—figure supplement 1). Thus staining with Tbr1, a layer 6 marker, revealed a distinctive band in the deeper layers of the cortex in both controls and Gsk3:Neurod6 mutants. In contrast, we noted clear abnormalities in the localization of Cux1 expressing neurons that normally populate Layers 2/3 (Figure 1—figure supplement 1). A clear band of Cux1 positive neurons has formed in controls by E16. In contrast Gsk3:Neurod6 mice exhibit a dispersion of Cux1 cells with fewer neurons reaching the outermost layer, even at this early developmental stage.


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)

Migration defect apparent by E16 after Gsk3 deletion in cortical excitatory neurons.Coronal cryostat sections at E16. Layer 6 TBR1 neurons populate appropriate layers in control and Gsk3:Neurod6 mutants. Cux-1 (red) expressing neurons, marker for upper layer 2/3 neurons, are mislocalized in Gsk3:Neurod6 mutant coronal sections. L1 staining labels axon tracts.DOI:http://dx.doi.org/10.7554/eLife.02663.004
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1s1: Migration defect apparent by E16 after Gsk3 deletion in cortical excitatory neurons.Coronal cryostat sections at E16. Layer 6 TBR1 neurons populate appropriate layers in control and Gsk3:Neurod6 mutants. Cux-1 (red) expressing neurons, marker for upper layer 2/3 neurons, are mislocalized in Gsk3:Neurod6 mutant coronal sections. L1 staining labels axon tracts.DOI:http://dx.doi.org/10.7554/eLife.02663.004
Mentions: To explore neuronal functions of GSK-3, we first assessed cortical lamination at E16, a time of rapid neuronal migration along radial glial processes. Deep layer neurons appeared to be normally positioned (Figure 1—figure supplement 1). Thus staining with Tbr1, a layer 6 marker, revealed a distinctive band in the deeper layers of the cortex in both controls and Gsk3:Neurod6 mutants. In contrast, we noted clear abnormalities in the localization of Cux1 expressing neurons that normally populate Layers 2/3 (Figure 1—figure supplement 1). A clear band of Cux1 positive neurons has formed in controls by E16. In contrast Gsk3:Neurod6 mice exhibit a dispersion of Cux1 cells with fewer neurons reaching the outermost layer, even at this early developmental stage.

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