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. 2020 Jul 22;11:3669. doi: 10.1038/s41467-020-17382-3

Fig. 7. Olig2+ progenitors with Erk/MAPK activation underlie clonal expansion in the SVZ.

Fig. 7

a Copy-number variations (CNVs) of Nf1 gene were shown in the three Type 2 cases. Blue represents copy loss/deletion, while red represents copy gain/amplification. b Western blotting of cell lines from the samples described above showed Nf1 protein levels. Red arrow indicates the histologically normal Mouse 6 SVZR: a control with normal levels of Nf1 expression. Source data are provided as a Source data file. c–i Control (n = 6), p53R172HCKO (n = 3) and p53∆E5–6CKO (n = 14) mice at age 5–7 months were injected with BrdU to detect proliferating cells in tumor-free brains. White dashed lines in (c, e, f) mark the areas of SVZ and/or RMS in the stem-cell niche. c, d Co-labeling of p-Erk and BrdU in the SVZ. Arrows indicate p-Erk+BrdU+ cells (yellow), only observed in the mutant. Arrowheads indicate p-Erk+BrdU− cells (green), observed in the control. Insets show high magnification in the SVZ. Quantifications are shown in (d). e Co-labeling of: p-Erk and BrdU; BrdU and p53 in early glioma-like clusters. Arrows indicate p-Erk+BrdU+, p53R172HBrdU+, or p53∆E5–6BrdU+ cells. Arrowheads indicate p-Erk+BrdU− cells. f Co-labeling of Olig2 and BrdU in the SVZ (left) and early glioma-like clusters (right). Arrows indicate Olig2+BrdU+ cells. g–i Co-labeling of p-Erk/Olig2 low- (left) and high- (middle, boxed areas in left) magnification, and p53/Olig2 (right) in the SVZ (g); early glioma-like cluster (h). Arrows indicate p-Erk+Olig2+ or p53∆E5–6Olig2+ cells. Arrowheads indicate p-Erk+Olig2− cells. The quantification of p-Erk+Olig2+ cells is shown in (i). j Representative early glioma-like clusters in the olfactory bulb from p53ΔE5–6CKO brains (n = 7) were labeled with: p-Erk; p53/Ascl1; p53/Ezh2; and Olig2/BLBP. Arrows indicate p53∆E5–6Ascl1+ or p53∆E5–6Ezh2+ or Olig2+BLBP+ cells. Data are presented as a dot plot with mean ± SEM. Unpaired, two-tailed Student’s t test was used for statistical analysis in (d, i). **p < 0.01, ***p < 0.001. SVZ subventricular zone, LV lateral ventricle, OB olfactory bulb, RMS rostral migratory stream, CC corpus callosum, SE short exposure, LE long exposure. DAPI is a nuclear counterstain. Scale bars: 50 µm.