How Sox2 maintains neural stem cell identity.

The transcription factor Sox2 [SRY (sex-determining region Y)-box 2] is expressed at the earliest developmental stages in the nervous system and functions as a marker protein for neural development. Sox2 is found in embryonic neural stem cells as well as in virtually all adult neural stem cells of the subventricular region and the subgranular zone of the hippocampus. Gain-of-function and loss-of-function experiments in transgenic animals revealed a key role for Sox2 in the maintenance of neural stem cell properties, including proliferation/survival, self-renewal and neurogenesis. A limited set of Sox2-responsive target genes have been identified, including the genes encoding the neural stem cell marker nestin and the signalling molecule sonic hedgehog. In this issue of the Biochemical Journal, Feng et al. identified the survivin gene as a target for Sox2 in neural stem cells. Survivin protects cells from programmed cell death and functions as a regulator of cell division. The regulation of survivin expression by Sox2 explains why the reduction of the Sox2 concentration in neural stem cells is accompanied by a reduced proliferation of the cells and an induction of apoptosis. It would be of interest to know whether the Sox2-survivin connection is a common scheme to maintain the 'stemness' identity of other stem/progenitor cells.