As new blood vessels form, extensive proliferation of the endothelial cells that line them takes place just behind the sprouting tip of the vessel. Wilhelm et al.2 show that, in these endothelial cells, the transcription factor FOXO1 is located in the cytoplasm, possibly as a result of having been phosphorylated (P) through the activity of the PI3K–AKT signalling pathway that is induced when vascular endothelial growth factor A (VEGFA) binds to its receptor (VEGFR2). As a consequence, FOXO1 cannot exert its function, described by the authors, in inhibiting the transcription factor MYC, which remains in the nucleus. The resulting enhanced MYC activity leads to increased cellular metabolism, growth and proliferation. By contrast, vessel maturation, which occurs more centrally in the vascular network, coincides with cessation of growth-factor signalling. Presumably at this stage, FOXO1, now non-phosphorylated, moves to the nucleus and inhibits MYC, thereby inducing endothelial-cell quiescence.