Figure 3. Increased gene expression and proliferation in the MGE of the Ts65Dn ventral telencephalon.

(a, b) Lhx6 expression was increased in the MGE of Ts65Dn brain at E13.5 and E14.5. Scale bar, 200 μm. See Supplementary figure 5 for additional markers. (c, d) E13.5 timed pregnant Ts65Dn females were injected (intraperitoneally) with BrdU to label a cohort of neural progenitors in S-phase and embryos were harvested 24 h later. (c) A representative section stained with antibodies to BrdU (green) and TUJ1 (red). Scale bar, 200 μm. (d) The fraction of cells labeled with both BrdU and TUJ1 (BrdU⁺/TUJ1⁺; newly generated neurons) 24 h after pulse label is 36% higher in the MGE of Ts65Dn. No significant change in LGE or CGE neurogenesis was observed in Ts65Dn brains, suggesting that increased neurogenesis was specific to the Ts65Dn MGE during this period of time. (e, f) The cumulative labeling plots for MGE progenitors at E13.5 and E14.5 demonstrate that the labeling index (percentage of BrdU⁺ cells) rises precipitously until reaching saturation at the GF value, which represents the proportion of the precursor cells that are participating in the cell cycle. The time to reach saturation defines the T_c-T_s value, which was normal in Ts65Dn (see also Supplementary Table 2). (g, h) Distribution of PH3-labeled M-phase cells in the MGE at E14.5 and E15.5. Starting from the ventricular border, the MGE was divided into 15 bins each 20 μm in thickness. Scale bar, 100 μm. The number of mitotic cells in the SVZ of Ts65Dn MGE was increased compared to euploid indicating an increase in abventricular mitoses in Ts65Dn. Data points represent mean ± s.d. (n=3–6 mice for each age and group). *p<0.05; by unpaired two-tailed t-test.