Mechanisms for Oxygen‐Mediation of Body Size

Abstract

Hypoxic‐rearing reduces the adult body size of animals, but the mechanisms responsible remain poorly understood. Holometabolous insects are important models for understanding the regulation of body size. Here we focus on how hypoxic rearing reduces final body size of Drosophila melanogaster. Larval D. melanogaster approximately triple their body mass during the last larval instar. We tested the hypothesis that functional hypoxia develops over time within the instar. Later instar animals had higher whole‐body copy numbers of HIFalpha and HIFbeta RNA and greater quantities of HIFalpha protein (Westerns), providing clear evidence that HIF signaling emerges late in the instar. Later‐instar animals also had greater expression of lactate dehydrogenase genes, and higher capacities for production of lactate, though not higher levels of whole‐body lactate, suggesting that functional hypoxia is not so extreme as to trigger anaerobic metabolism. However, CO2 emission rates increased in response to hyperoxia in late but not early‐instar larvae, providing strong evidence of oxygen limitation of metabolism. Hyperoxia reduced, and hypoxia elevated the RNA copy number of prolyl hydroxylase (whole body), a downstream target of HIF‐signaling. In sum, late‐instar normoxic‐reared larvae experience functional hypoxia, and whole‐body HIF‐signaling is increased with hypoxic‐rearing. Next, to understand the link between functional hypoxia and developmental transitions, we tested whether HIF signaling in the prothoracic glands (which produce ecdysone, aka molting hormone) affects development rate or adult size, using the GAL4‐UAS system to reduce or increase HIF signaling in this endocrine gland. Knockdown of HIF signaling in the prothoracic glands strongly delayed pupariation in 10% but not 21% oxygen atmospheres. Thus HIF‐signaling in the prothoracic gland appears to be an important factor in triggering Drosophila pupariation at a smaller body size in hypoxia, but we found no evidence that this is a key pathway for of the control of molting and size in normoxia.Support or Funding InformationSupported by NSF IOS 1256745.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.