Cell cycle length influences the balance between progenitor maintenance and differentiation in the nervous system, although the mechanism for this is unknown. Here, Anna Philpott and co-workers show that multi-site phosphorylation of neurogenin 2 (Ngn2), a master regulator of neuronal development, controls neuronal differentiation in response to cell cycle lengthening in Xenopus embryos and in mammalian P19 cells (see ). The researchers show that, in Xenopus extracts, Ngn2 phosphorylation is regulated by the cell cycle, and analyses of HeLa cell extracts show that Ngn2 is phosphorylated on multiple sites by cyclin-dependent kinases (cdks). The phosphorylation of Ngn2, they report, reduces its ability to induce neuronal differentiation in vivo, and this is due to the decreased ability of phosphorylated Ngn2 to bind to its target promoters. The authors thus propose a model in which multi-site phosphorylation of Ngn2, which is quantitatively sensitive to cell cycle length, is used as a way to interpret cdk levels in order to control neuronal differentiation in response to cell cycle lengthening during development.
