Fig 5.
Gliomagenesis within the adult neurogenic niches requires TLX. (A) Kaplan-Meier survival curves. Autopsy and histological analyses were performed at the endpoint of the tumor study. The total survival includes mice that developed gliomas and nonglioma tumors (n = 51 for Cre; Ptenf/+; p53f/f and n = 53 for Cre; Tlxf/fPtenf/+; p53f/f). The number of glioma-bearing mice was used to plot glioma-free survival (n = 14 for Cre; Ptenf/+; p53f/f and n = 20 for Cre; Tlxf/f; Ptenf/+; p53f/f). (B) Locations of gliomas within the brain parenchyma were examined by histology. +NSC indicates gliomas directly associated with the neurogenic niches. −NSC indicates gliomas not in the vicinity of the neurogenic niches. (C) Histology of the glioma-bearing mouse brains. The neurogenic regions in Tlx mutant mice lacked tumor cells (LV, lateral ventricle; DG, dentate gyrus). Tumor boundaries were circumscribed in Tlx mutant mice. Staining for pAKT showed enhanced AKT signaling within the tumor mass. Higher magnification views were taken from the boxed regions. (D) Histological features of malignant gliomas. These features include significant cellular pleomorphism (panels 1, 2, 4, 5, and 7), necrosis (panels 3, 8, and 10), pseudopalisading (panel 10), and occasional areas of microvascular proliferation (panels 4, 5, and 9). Arrows in panels 2 and 7 point to giant cells, whereas arrowheads in panels 2 and 7 point to cells with mitotic figures (also see the insets). V and mV indicate vasculature and areas with microvasculature features, respectively. N and H show areas with necrosis and hemorrhage, respectively. Scale bar, 50 μm.