Zfp536 expression rescues the enhanced proliferation of cortical NPCs caused by SenZfp536 knockdown. A–H E13.5 mouse cortices were electroporated with indicated vectors and transduced cells were labeled with EGFP; embryos were sacrificed at E16.5 for immunofluorescent analyses. A, E Spatial distribution of transduced cells. VZ/SVZ immunofluorescent images and quantification for BrdU (B, F), PAX6 (C, G), and SOX2 (D, H) are displayed. White arrows, co-labeled cells. For VZ/SVZ in E, F = 36.22, P < 0.0001; for IZ in E, F = 30.23, P < 0.0001; for CP in E, F = 46.32, P < 0.0001. For F, F = 33.35, P < 0.0001; for G, F = 38.23, P < 0.0001. for H, F = 44.24, P < 0.0001 (one-way ANOVA followed by Tukey’s multiple comparison test). Samples per experiment: Scrambled, n = 6; shSenZfp536 n = 4; pCIG, n = 7; Zfp536, n = 3; shSenZfp536 + Zfp536, n = 5. Scale bars, 50 μm. *P < 0.05; **P < 0.01; ***P < 0.001; ns, not significant. Results are presented as mean ± SEM. I Model showing that SenZfp536 negatively regulates the self-renewal of cortical NPCs by cis-activating Zfp536.