Fig. 5: Fgf10 and Flrt1/Flrt3 loss enhances gyri-like cortex folding.
From: Cortex folding by combined progenitor expansion and adhesion-controlled neuronal migration
a Macroscopic sulci and gyri in E17.5 Fgf10 tKO embryo. Dashed rectangles are shown with higher magnification on the right, sulci and gyri are indicated by arrowheads. Scale bars, 500 μm. b-b” E17.5 Fgf10 tKO brain. c-c” E17.5 Fgf10 dKO brain stained with Satb2, Ctip2, and DAPI. Dashed lines indicate gyri in both hemispheres. Higher magnifications on the right (b’, b”, c’, c”). Scale bars, b, c 100 μm, b’-b” and c’-c” 50 μm. d Folding penetrance of E17.5 Fgf10 lx/lx, Fgf10 cKO, CTL (Flrt1−/−;Flrt3lx/+), Flrt1/3 dKO, Fgf10 dKO, and Fgf10 tKO. All folds located on the lateral cortex. e Table of cortical folding penetrance at E17.5. Brains were analyzed for the presence of one or more gyri, as in (d). Fgf10 lx/lx embryos were littermate controls for the Fgf10 cKO. To increase the number of Fgf10 cKO embryos, mothers were Foxg1-Cre;Fgf10 lx/lx. Germline Cre activity may explain folding in two Fgf10 lx/lx embryos. f Statistical analysis of synergistic vs additive effects on number of folds in Fgf10 single and Flrt1/3 dKO vs Fgf10 dKO or tKO. Additive effect: sum of mean cortical folds in Fgf10 single and Flrt1/3 dKO, corrected for background in Fgf10 lx/lx controls. Data are represented as a box plot (as in Fig. 1). one-sample Wilcoxon test with one-sided alternative. g Representative image of a Fgf10 tKO embryo depicting the quantification of the Gyrification Index (GI). Red line: de facto cortical surface; blue line: minimal (hypothetical) length. Scale bar, 100 μm. h GI quantification in E17.5 embryos. n = 6 brains/3 litters Fgf10 cKO (gray), n = 4 brains/3 litters Flrt1/3 dKO (black) and n = 15 sections from 7 brains/5 litters Fgf10 tKO (red) in the rostral cortex. Data are shown as mean ± SEM. one-way ANOVA with Tukey’s post hoc analysis.
