Figure 2. Neural progenitor proliferation and neurogenesis is altered in homozygous disc/disc embryos.

(a) Immunofluorescent analysis of Pax6 expression in the neocortical neuroepithelium at E12.5 and E14.5. Yellow dashed lines in the E12.5 brains outline the measured area of the Pax6⁺ ventricular zone (VZ). Red lines at E14.5 highlight the lateral thinning of the VZ. (b) Quantification of the Pax6⁺ VZ reveals significant increases in the disc/disc mutant for either stage. In contrast, density of Pax6⁺ cells is not altered in the disc/disc embryos (c, d). (e - h) Immunofluorescent area and density analysis of Tbr2⁺ intermediate progenitors reveals significant reductions in both domains. (i, j) 24 h EdU pulse-chase assay reveals a reduction in total neuronal output [EdU⁺/Ki67⁻ cells basal to the subventricular zone (SVZ)] per hemisphere but an increase in the Q-fraction of cells that have exited the cell cycle. (k) Representative coronal sections of mediolateral cortex illustrate the outcome of time-shifted dual thymidine-labeling experiment and the distribution of EdU-, BrdU-, and Ki67-labeled cells at E13.5. (l) Quantification of S phase length (T_S) and total cell cycle length (T_C) determined significant decreases in the disc/disc mutants relative to WT. All statistical analysis by Student’s t-test. Bar diagrams show mean and SEM, indicate n for either genotype, and calculated p-values of significant changes (asterisks). CP, Cortical plate; Cx, cerebral cortex; IZ, intermediate zone; LV, lateral ventricles; Th, thalamus. Scale bar in a is 200 μm, in c 10 μm, in e 100 μm, in g 20 μm, in i 100 μm and 50 μm, and in k 20 μm.