Hypoxia is often regarded as a stressful condition occurring to plants during submergence. Instead, by using genetically encoded reporters and miniaturized oxygen probes, we found that the stem cells in the Arabidopsis shoot apex are embedded in a hypoxic niche, even when plants grow under aerobic conditions. This feature is not exclusive to Arabidopsis, but was also found in Solanum lycopersicum and Crassula ovata, indicating that it is a common feature of plant shoot meristems. Hyperoxia treatments or knocking out of several plant cysteine oxidase genes, which perturbs the perception of normoxia, led to defects in organ initiation rate and leaf morphology. We also observed that local hypoxia in the shoot stem cells prevents proteolysis of a novel N-degron pathway substrate: LITTLE ZIPPER 2 (ZPR2). This protein regulates the activity of HD-ZIP III transcription factors, which are involved in the determination of leaf polarity, embryogenesis, vasculature development and meristem activity. Both genetic inactivation of ZPR2 and ectopic stabilization of this protein impaired meristem activity. Thus, local hypoxic concentrations in the shoot apex do not appear to be harmful, but rather act
as a spatial developmental cue to regulate meristem activity.