The time of timing: how Polycomb proteins regulate neurogenesis

The study of mammalian corticogenesis has revealed a critical role for Polycomb group (PcG) factors in timing the execution of developmental choices. Meanwhile, the study of post-translational modifications of PcG factors marks a symmetrical point, namely that the activity of PcG proteins is itself timed in a manner that links progression through the cell cycle to targeting of downstream genes. Finally, in a third symmetrical twist, the studies that dissect the timing of neural fate by Polycomb are also uncovering the importance of timing in the experimental mutation, since ablation of the same PcG member at different developmental stages yields dramatically different results. Here, I weave together these three lines of evidence and develop a unifying model that clarifies the dynamics of Polycomb function in neural development and defines the salient challenges ahead.