Figure 7.

Inhibition of PKG activity with KT5823 reduces interneuron migration from the MGE to the cortex in E13.5 telencephalic slices. A–B″, Slice electroporation migration assay. Cells were visualized by transfecting a GFP expression vector into the MGE (A–B″) by electroporation; migration into the LGE and cortex was assessed after 7, 19, and 41 h. C, Histogram showing quantification of the number of cells migrating to the cortex from MGE in slices. Slices were grown in either DMSO or 25 μm KT5823. CX, Cortex. Data are the mean ± SEM. *p ≤ 0.05 (paired Student's t test). **p ≤ 0.01 (paired Student's t test). A″, B″, p = 7.5 × E-6. Additionally, inhibition of PKG activity with KT5823 inhibits cell migration from explants of the E13.5 MGE and CGE, assessed using Matrigel explants and Boyden chamber assays. D–I, Matrigel explant cell migration assays of E13.5 MGE and CGE comparing DMSO (D, G), 100 μm ODQ (E, H), and 25 μm KT5823 (F, I). J, K, Histograms reporting the percentage change in MGE (J) and CGE (K) explant outgrowth as a function of ODQ and KT5823 using one-way ANOVA followed by Bonferroni post test. DMSO versus ODQ, p = 3.26E-07; DMSO versus KT, p = 6.06E-07. K, DMSO versus ODQ, p = 3.57E-05; DMSO versus KT, p = 7.47E-05. L, Boyden chamber assay showing that both ODQ and KT5823 inhibit migration. Data are the mean ± SEM. *p < 0.05 (one-way ANOVA followed by Bonferroni post test). **p < 0.01 (one-way ANOVA followed by Bonferroni post test). DMSO versus ODQ, p = 1.4 × E-6; DMSO versus KT, p = 2.1 × E-5. Scale bars: A–I, 500 μm.