By combining sophisticated transgenic gain- and loss-of-function strategies with an innovative CRISPR-Cas 9 GBM mouse model in which fluorescently labeled brain tumors are induced from radial glia in the dorsal SVZ, we demonstrate that ASCL1 and OLIG2 are prominent drivers of brain tumor initiation, proliferation, migration, and cell type specification. The gene discussed is ASCL1; the disease is glioblastoma.