Limits...
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.

Show MeSH

Related in: MedlinePlus

Gsk3 overexpression enhances radial migration.(A) E19.5 coronal sections showing normal migration after in utero electroporation of Neurod1-Cre and lox-STOP-lox-Ai9 (red neurons) and (B) Coronal sections showing abnormal neuronal migration after electroporation of Neurod1-Gsk3b and Neurod1-GFP (green neurons). Enhanced migration is apparent in B. Scale bar = 200 μm. (C) E19.5 quantification of migration in control and Gsk3 over-expressing neurons using 8 bin analysis as previously described. Significantly more Gsk3 over-expressing neurons were found in the outermost bin 8 and fewer Gsk3 over-expressing neurons populated bin 6. p-values shown in figure, unpaired t-test. (control n = 2 mice from two individual litters, 1276 neurons vs Gsk3 overexpression n = 3 mice from two individual litters, 1959 neurons).DOI:http://dx.doi.org/10.7554/eLife.02663.006
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4109311&req=5

fig2s1: Gsk3 overexpression enhances radial migration.(A) E19.5 coronal sections showing normal migration after in utero electroporation of Neurod1-Cre and lox-STOP-lox-Ai9 (red neurons) and (B) Coronal sections showing abnormal neuronal migration after electroporation of Neurod1-Gsk3b and Neurod1-GFP (green neurons). Enhanced migration is apparent in B. Scale bar = 200 μm. (C) E19.5 quantification of migration in control and Gsk3 over-expressing neurons using 8 bin analysis as previously described. Significantly more Gsk3 over-expressing neurons were found in the outermost bin 8 and fewer Gsk3 over-expressing neurons populated bin 6. p-values shown in figure, unpaired t-test. (control n = 2 mice from two individual litters, 1276 neurons vs Gsk3 overexpression n = 3 mice from two individual litters, 1959 neurons).DOI:http://dx.doi.org/10.7554/eLife.02663.006

Mentions: To further assess functions of GSK-3 in radial migration, we over-expressed Gsk3b in newly born cortical neurons using a pNeurod1 (Neurod1) vector (Guerrier et al., 2009). Co-electroporation of Neurod1-Cre and lox-STOP-lox Ai9 in control embryos at E15 (Figure 2—figure supplement 1A) was compared to co-electroporation of Neurod1-Gsk3b and Neurod1-Egfp in experimental embryos (Figure 2—figure supplement 1B). Importantly, over-expression of Gsk3b did not inhibit migration as might have been expected from prior studies (Asada and Sanada, 2010). In fact, Gsk3b over-expression enhanced neuronal migration and resulted in greater than normal numbers of neurons populating the outermost layers of the cortex by E19.5 (Figure 2—figure supplement 1C).


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)

Gsk3 overexpression enhances radial migration.(A) E19.5 coronal sections showing normal migration after in utero electroporation of Neurod1-Cre and lox-STOP-lox-Ai9 (red neurons) and (B) Coronal sections showing abnormal neuronal migration after electroporation of Neurod1-Gsk3b and Neurod1-GFP (green neurons). Enhanced migration is apparent in B. Scale bar = 200 μm. (C) E19.5 quantification of migration in control and Gsk3 over-expressing neurons using 8 bin analysis as previously described. Significantly more Gsk3 over-expressing neurons were found in the outermost bin 8 and fewer Gsk3 over-expressing neurons populated bin 6. p-values shown in figure, unpaired t-test. (control n = 2 mice from two individual litters, 1276 neurons vs Gsk3 overexpression n = 3 mice from two individual litters, 1959 neurons).DOI:http://dx.doi.org/10.7554/eLife.02663.006
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2s1: Gsk3 overexpression enhances radial migration.(A) E19.5 coronal sections showing normal migration after in utero electroporation of Neurod1-Cre and lox-STOP-lox-Ai9 (red neurons) and (B) Coronal sections showing abnormal neuronal migration after electroporation of Neurod1-Gsk3b and Neurod1-GFP (green neurons). Enhanced migration is apparent in B. Scale bar = 200 μm. (C) E19.5 quantification of migration in control and Gsk3 over-expressing neurons using 8 bin analysis as previously described. Significantly more Gsk3 over-expressing neurons were found in the outermost bin 8 and fewer Gsk3 over-expressing neurons populated bin 6. p-values shown in figure, unpaired t-test. (control n = 2 mice from two individual litters, 1276 neurons vs Gsk3 overexpression n = 3 mice from two individual litters, 1959 neurons).DOI:http://dx.doi.org/10.7554/eLife.02663.006
Mentions: To further assess functions of GSK-3 in radial migration, we over-expressed Gsk3b in newly born cortical neurons using a pNeurod1 (Neurod1) vector (Guerrier et al., 2009). Co-electroporation of Neurod1-Cre and lox-STOP-lox Ai9 in control embryos at E15 (Figure 2—figure supplement 1A) was compared to co-electroporation of Neurod1-Gsk3b and Neurod1-Egfp in experimental embryos (Figure 2—figure supplement 1B). Importantly, over-expression of Gsk3b did not inhibit migration as might have been expected from prior studies (Asada and Sanada, 2010). In fact, Gsk3b over-expression enhanced neuronal migration and resulted in greater than normal numbers of neurons populating the outermost layers of the cortex by E19.5 (Figure 2—figure supplement 1C).

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