Fig. 3. Activation of transgenic Pax6 disturbs the mitotic cell cycle. (A,A') HE staining of P23 cross-sections of JoP6 control and JoP6;Emx1^IREScre cortex (cx). The size of the JoP6;Emx1^IREScre cortex is significantly diminished, but cortical layering is preserved. Scale bars: 0.5 mm. (B,B') Coronal 5 µm sections of E11.0 JoP6 control and JoP6;Emx1^IREScre cortex immunostained for BrdU and DAPI after a 30-minute BrdU pulse. Estimated BrdU labeling indices reveal a significant inhibition of the proliferation rate in the MP and DP of the JoP6;Emx1^IREScre cortex as compared with the JoP6 control. The frames indicate the equally sized areas used for determination of the BrdU labeling index of the genotypes compared. (C-D') Patterns of BrdU pulse labeling of cortical progenitors at stage E11.0 for 90 minutes (C,C') and 6 hours (D,D') in JoP6 control (C,D) and JoP6;Emx1^IREScre mice (C',D'). The arrows in C point to nuclei in the control cortex that were labeled at the end of their S phase and underwent mitosis thereafter, as indicated by their diluted content of BrdU. Nuclei of such appearance are scarce in the JoP6;Emx1^IREScrecortex (C'; arrowheads point to cell aggregates). Note the severe distortion of the interkinetic nuclear migration in the JoP6;Emx1^IREScre cortex, in which, even after a 6-hour BrdU pulse, many nuclei are still in the basal VZ (arrows in D'). (E,E') Immunolabeling of pHH3 at stage E14.5 reveals significantly fewer mitotic cells at the apical surface of the VZ in JoP6;Emx1^IREScre as compared with JoP6 mice.