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
Quantification of lamination in other signaling mutants.(A–D) P0 quantification of Cux1 expressing neurons using 8 Bin quantification in conditional mutants and control shown in Figure 6. (A) Ctnnb1Ex3:Neurod6, (B) Stk11:Neurod6, (C) Cdc42:Neurod6, (D) Pten:Neurod6. (n = 2 het control mice, n = 2 CKO mice per line). Between 2000 and 3000 Cux1 neurons were scored in each of the control pairs and each of the mutant pairs.DOI:http://dx.doi.org/10.7554/eLife.02663.016
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6s1: Quantification of lamination in other signaling mutants.(A–D) P0 quantification of Cux1 expressing neurons using 8 Bin quantification in conditional mutants and control shown in Figure 6. (A) Ctnnb1Ex3:Neurod6, (B) Stk11:Neurod6, (C) Cdc42:Neurod6, (D) Pten:Neurod6. (n = 2 het control mice, n = 2 CKO mice per line). Between 2000 and 3000 Cux1 neurons were scored in each of the control pairs and each of the mutant pairs.DOI:http://dx.doi.org/10.7554/eLife.02663.016

Mentions: To determine the role of GSK-3 regulation of β-catenin in developing cortical excitatory neurons, we utilized a β-catenin (Ctnnb1) mouse that harbors loxP sites flanking exon 3 (Ctnnb1Ex3:Neurod6) (Harada et al., 1999). Exon 3 encodes the residues that GSK-3 phosphorylates to signal β-catenin degradation; thus deleting exon 3 stabilizes β-catenin. Using a β-catenin antibody directed at the residues encoded by exon3 verified a reduction in this protein fragment at P0 as expected after Neurod6-mediated recombination (Figure 6C,H). Migration of Cux1 neurons was entirely normal in these animals (Figure 6A, Figure 6—figure supplement 1A). Further, in contrast to Gsk3:Neurod6, Ctnnb1Ex3:Neurod6 mice survive, breed, and have no overt behavioral phenotype. They display a rostral midline defect resulting from lack of the hippocampal commissure (data not shown), as seen in other models using stabilized β-catenin (Chenn and Walsh, 2003).10.7554/eLife.02663.015Figure 6.Lamination in other signaling mutants.


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)

Quantification of lamination in other signaling mutants.(A–D) P0 quantification of Cux1 expressing neurons using 8 Bin quantification in conditional mutants and control shown in Figure 6. (A) Ctnnb1Ex3:Neurod6, (B) Stk11:Neurod6, (C) Cdc42:Neurod6, (D) Pten:Neurod6. (n = 2 het control mice, n = 2 CKO mice per line). Between 2000 and 3000 Cux1 neurons were scored in each of the control pairs and each of the mutant pairs.DOI:http://dx.doi.org/10.7554/eLife.02663.016
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6s1: Quantification of lamination in other signaling mutants.(A–D) P0 quantification of Cux1 expressing neurons using 8 Bin quantification in conditional mutants and control shown in Figure 6. (A) Ctnnb1Ex3:Neurod6, (B) Stk11:Neurod6, (C) Cdc42:Neurod6, (D) Pten:Neurod6. (n = 2 het control mice, n = 2 CKO mice per line). Between 2000 and 3000 Cux1 neurons were scored in each of the control pairs and each of the mutant pairs.DOI:http://dx.doi.org/10.7554/eLife.02663.016
Mentions: To determine the role of GSK-3 regulation of β-catenin in developing cortical excitatory neurons, we utilized a β-catenin (Ctnnb1) mouse that harbors loxP sites flanking exon 3 (Ctnnb1Ex3:Neurod6) (Harada et al., 1999). Exon 3 encodes the residues that GSK-3 phosphorylates to signal β-catenin degradation; thus deleting exon 3 stabilizes β-catenin. Using a β-catenin antibody directed at the residues encoded by exon3 verified a reduction in this protein fragment at P0 as expected after Neurod6-mediated recombination (Figure 6C,H). Migration of Cux1 neurons was entirely normal in these animals (Figure 6A, Figure 6—figure supplement 1A). Further, in contrast to Gsk3:Neurod6, Ctnnb1Ex3:Neurod6 mice survive, breed, and have no overt behavioral phenotype. They display a rostral midline defect resulting from lack of the hippocampal commissure (data not shown), as seen in other models using stabilized β-catenin (Chenn and Walsh, 2003).10.7554/eLife.02663.015Figure 6.Lamination in other signaling mutants.

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