Nutrient restriction (NR) reduces the proliferation of neural progenitor cells (NPCs) in the developing Xenopus brain, but the molecular mechanisms that regulate this phenomenon have been unclear. Now, Caroline McKeown and Hollis Cline use CldU incorporation to label dividing NPCs and characterise their response to NR. In fed animals, CldU is diluted through successive cell divisions decreasing the overall fluorescence intensity of labelled cells. In NR conditions, however, NPCs are brighter, suggesting that the cells are quiescent. Through CldU/pH3 pulse-chase experiments, the authors reveal that NR arrests NPCs at the G2 stage, where cells have higher DNA content. This stasis is reversible and cells can re-enter the cell cycle at M phase 16 h after feeding. To elucidate a mechanism, the researchers inhibited mTOR signalling, which increases in response to feeding. They reveal that mTOR activity is not necessary to cause NR-induced cell cycle arrest, but is required for arrested NPCs to start proliferating again. Finally, treatment with an insulin-mimetic drug is sufficient to restart proliferation within 4 h, even without reintroducing food. Together, these results provide evidence for an adaptive strategy to control brain development in response to nutrient availability through a G2-arrest mechanism.
