Sox2 is expressed highly in the neuroepithelium of the developing CNS and has been shown to function in neural stem cells. Because Sox2-null mutant mice fail to develop beyond implantation, the role of SOX2 in the CNS has lacked validation. A new genetic model addresses the role of SOX2 in the adult brain and provides evidence that it is involved in the maintenance of neurons in specific regions, in the proliferation and/or maintenance of neural stem cells, and in neurogenesis.