Figure 7. Changes in Gli3^FL/Gli3^Rep ratio correspond with changes in cell cycle length over cortical development.

(A) Gli3^FL/Gli3^Rep ratio and Cyclin D1 protein levels decrease over cortical development analyzed by western blot. (B) Expression of Shh target genes in E12.5, E14.5 and E17.5 coronal sections. Fgf15 and CyclinD1 decrease over cortical development evident by radioactive in situ hybridization. (C) Model of cell cycle length control in the cerebral cortex. A high Gli3^FL/Gli3^Rep ratio present during early corticogenesis leads to high levels of CyclinD1 and Fgf15 expression and a short G1 phase. A decreased Gli3^FL/Gli3^Rep ratio present later in development leads to a decrease in Cyclin D1 and no Fgf15 expression and a much longer G1 phase. Kif3a^cko or Gli3 mutants no longer undergo normal developmental changes and mimic the early state.