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. 2010 Apr 1;24(7):683–695. doi: 10.1101/gad.560310

Figure 5.

Figure 5.

Brain tumor development from SVZ of Tlx-OE mice upon loss of p53. (A) Two-month-old mice were injected with BrdU 2 h before sacrifice, and coronal sections were stained with Ki67. Note Ki67-positive cells outside of the SVZ in Tlx-OE;p53−/− mice (arrows). (B) Two-month-old mice were injected with BrdU 2 h before sacrifice, and coronal sections were stained with BrdU. Arrows indicate BrdU-positive cells in the striatum of Tlx-OE;p53−/− mice. (C) Two-month-old mice were injected with BrdU 2 h before sacrifice, and coronal sections were stained with DCX (red) and Ki67 (green). Note that p53−/− mice do not show migration of the SVZ proliferating cells toward the striatum in comparison with Tlx-OE;p53−/− mice (arrows). (D) Three-month-old Tlx-OE;p53−/− mice develop hyperproliferative lesions as indicated by H&E and Ki67 staining. (E) Tlx-OE;p53−/− mice spontaneously develop gliomas. (Panel a) Tumor sections stained with H&E. Note a highly cellular, small cell glioma with diffuse infiltration of the adjacent brain. Arrows indicate tumor cell clusters migrating to neighboring regions. Bar, 100 μm. (Panel b) Tumor sections stained with H&E. Accumulation of tumor cell clusters in the subpial zone of the cortex (arrow). Bar, 50 μm. (Panel c) Strong expression of GFAP in tumors. Bar, 50 μm. (Panel d) The tumor cells are highly proliferative, as indicated by Ki67 staining. The proliferation index of the depicted tumor was ∼15%, with a higher density of Ki67-positive cells at the tumor periphery. Bar, 50 μm. (Panel e) More proliferating cells are located at the border of the tumor (arrow). Bar, 50 μm. (Panel f) Tumor sections stained with the Tlx antibody. Arrows indicate Tlx-positive cells. Bar, 50 μm. (Panel g) Interspersed NeuN-positive neurons in the tumor tissue (arrows). Bar, 50 μm. (Panel h) Perineuronal satellitosis characterized by tumor cells surrounding NeuN+ neurons (arrows). (Panel i) Mash1 immunoreactivity in Tlx-induced tumors. Bar, 15 μm. (Panel j) Some tumor cells are P-Akt-positive, indicating an alteration of the Pten/Pi3k/Akt pathway; the inset indicates a tumor-free striatal region. (Panel k) Nestin is highly expressed by Tlx overexpression-induced gliomas. (l) DCX is strongly expressed by infiltrating tumor cells.