Figure 2. Migration defects in Gsk3-deleted mice are persistent.

(A) P0:Cux 1 staining (red) in coronal sections of Gsk3^loxp:Neurod6 mutants and littermate heterozygote controls. Cux1-expressing neurons are localized to layer2/3 in controls (denoted by yellow dashed lines) while Cux1-expressing neurons are localized throughout the cortical plate in the mutants. (n = 5, scale bar = 100 μm). (B) Representative Western blot of P0 cortical lysates confirms strongly reduced GSK-3α and GSK-3β protein levels in Gsk3^loxp:Neurod6 mutants when compared to Gsk3a^loxp/loxpGsk3b^loxp/loxp controls. GAPDH was probed as a loading control (n = 3 control, n = 3 CKO). (C) P0 quantification of control and Gsk3^loxp:Neurod6 Cux1 neurons using 8 bin analysis spanning white matter (WM) to the pial surface (PS), (n = 2 het control, n = 2 CKO). (D–D') P7: Gsk3^loxp:Neurod6 mutants stained with Cux1 (red) show persistent altered lamination with Cux1-expressing neurons spread throughout all layers of the cortex. Littermate controls show normal Cux1 distribution in layer 2/3. Scale bar = 200 μm.

DOI: http://dx.doi.org/10.7554/eLife.02663.005

Figure 2—figure supplement 1. 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