A paper in this issue discloses the secret of eternal youth—at least for neural progenitors. During neurogenesis, self-renewing progenitor cells that reside in the ventricular zone of the developing CNS exit the cell cycle, migrate toward the marginal zone, and differentiate into neurons. Previous studies have identified transcription factors that promote the formation of new neurons by directing stem cells to stop dividing. However, the mechanisms responsible for countering differentiation to maintain a pool of undifferentiated neural progenitor cells have been less clear.

On pages 1162–1168, Jonas Muhr and colleagues report that the transcription factors Sox1, Sox2 and Sox3 are important for maintaining the progenitor cell pool in the chick spinal cord. They find that Sox-3 maintains neural progenitor cells in an undifferentiated state and suppresses neuronal differentiation. Sox1–3 proteins countered neurogenesis by repressing downstream differentiation signals from bHLH proteins, a family of proneural transcription factors. Moreover, when Sox1-3 target genes were actively repressed, independently of proneural activity, progenitor cells differentiated prematurely. The figure shows a coronal section of an embryonic chick spinal cord stained with Sox3 (green), NeuroM (red) and Tuj1 (blue). NeuroM is a bHLH protein, expressed during neurogenesis, whereas Tuj1 is a neuronal marker.

The Sox family of transcription factors are expressed by most stem cells in the developing CNS and are typically downregulated during differentiation. Sox genes are important in the generation of neuroblasts in Drosophila, and in maintaining precursor cells of the mouse blastocyst in a multipotent state. A Sox gene family member, Sox 10, expressed in migrating neural crest cells, maintains the multipotency of neural crest cells in culture. Moreover, Sox proteins are expressed in self-renewing stem cells in the adult CNS. Together with the work of Muhr and colleagues, these findings suggest that several Sox genes may keep cells from different origins in an undifferentiated state.