Figure 2. Chd7 regulates the proliferation and survival of cerebellar GCps.

(A and B) Dorsal whole-mount images of P21 Chd7^fl/fl cn and Math1-Cre Chd7^fl/fl GCp-specific conditional knockout (cko) mouse cerebella, anterior to the top. Note hypoplasia and abnormal foliation in the cko. (C–F) Cresyl violet–stained sagittal sections through the cerebellum, anterior to the left. Folia are numbered as in Figure 1. Note hypoplasia and abnormal folia indicated by an arrowhead and labeled in red in the cko. (G and H) Magnified view of the boxed areas in E and F with PC layers outlined by red broken lines. (I) Traced outlines of representative cerebellar sections from cn (black) and cko (blue) mice at the indicated time points. Foliation defects are first noted at E18.5 in the vermis and P2 in the hemispheres. Hypoplasia becomes evident in the vermis by E18.5 and hemispheres by P10 (see also Supplemental Figure 5). (J) Quantification of GCp proliferation in the P0 EGL by BrdU incorporation within a 1-hour time window. The BrdU labeling index for the indicated regions representing the fraction of BrdU-positive GCps in the EGL as counted in 100-by-100-μm areas. (K) The number of cleaved caspase-3–positive (CC3-positive) cells in the EGL per square millimeter of granule cell area at P7 is shown for vermis and hemispheres (n = 3 per genotype). *P < 0.05, **P < 0.01, ***P < 0.001, Student’s t test. Scale bars: 300 μm (A), 1 mm (C), 100 μm (G).