Fig. 9.

Ranbp1, a 22q11 gene implicated in cell cycle control, is necessary for normal cortical development. (Top left) Ranbp1^−/− embryos are dysmorphic at E10.5. Anomalies include a shortened telencephalic vesicle (bracket) and hypoplastic branchial arches. In addition, a subset of Ranbp1^−/− embryos is exencephalic. (Bottom left) At E14.5 Ranbp1^−/− embryos are visibly dysmorphic, including a smaller head and frequent eye defects. The brain, and particularly the cortex of Ranbp1^−/− embryos is substantially smaller at E14.5, as shown in dorsal view. (Right) Cortical precursor proliferation and neurogenesis is disrupted in the Ranbp1^−/− embryo. Proliferation of rapidly dividing neuroepithelial progenitors in the E10.5 Ranbp1^−/− embryo is diminished, shown here using PH3 labeling of mitotically active precursors (top right). At later stages proliferation of rapidly dividing Tbr2+ basal progenitors in the E14.5 cortex is diminished, as evidenced by decreased numbers of Tbr2+/BrdU+ double-labeled cells (middle right). These proliferative defects prefigure an overall loss in cortical size, as well as a selective loss of layer 2/3 neurons (bottom right). This change is seen clearly in the E17.5 cortex. The frequency of layer 2/3 projection neurons (labeled with Cux1) is diminished; however, the frequency of layer 5/6 projection neurons (labeled with Ctip2) is not significantly changed.

Figure adapted from Paronett et al. (2014).