Hypoxia and nitric oxide induce a rapid, reversible cell cycle arrest of the drosophila syncytial divisions

Cells can respond to reductions in oxygen (hypoxia) by metabolic adaptations, quiescence or cell death (1), The nuclear division cycles of syncytial stage Drosophila melanogaster embryos reversibly arrest upon hypoxia, We examined this rapid arrest in real time using a fusion of green fluorescent protein and histone 2A In addition to an interphase arrest, mitosis was specifically blocked in metaphase, much like a checkpoint arrest. Nitric oxide, recently proposed as a hypoxia signal in Drosophila, induced a reversible arrest of the nuclear divisions comparable with that induced by hypoxia. Syncytial stage embryos die during prolonged hypoxia, whereas post-gastrulation embryos (cellularized) survive (2, 3). We examined ATP levels and morphology of syncytial and cellularized embryos arrested by hypoxia, nitric oxide, or cyanide. Upon oxygen deprivation, the ATP levels declined only slightly in cellularized embryos and more substantially in syncytial embryos. Reversal of hypoxia restored ATP levels and relieved the cell cycle and developmental arrests. However, morphological abnormalities suggested that syncytial embryos suffered irreversible disruption of developmental programs. Our results suggest that nitric oxide plays a role in the response of the syncytial embryo to hypoxia but that it is not the sole mediator of these responses.