Metabolic shifts during growth deceleration in Drosophila imaginal wing discs

ABSTRACT: Growth during development is often characterised by progressive deceleration, as organisms, tissues, and organs approach their final size. Using transcriptomics analysis, we show that, during their two-day period of growth deceleration, wing imaginal discs of Drosophila undergo a progressive metabolic shift away from oxidative phosphorylation and towards glycolysis. We then develop a sensitive reporter of HIF-1a activity (a proxy for hypoxia), which allows us to show that imaginal discs become mildly, though increasingly, hypoxic during normal development, in normoxic conditions. As a result, HIF-1a dampens growth via transcriptional activation of scylla/REDD1, a negative regulator of TOR signalling. We find that overactivation of TOR signalling triggers a marked hypoxia response both cell-autonomously and in surrounding tissues. This suggests that, in wildtype animals, TOR activity imposes increasing pressure on oxygen supplies. Indeed, in the absence of HIF-1a, TOR signalling triggers JNK signalling, a marker of cellular stress. Moreover, TOR-induced stress is alleviated by a small increase is oxygen supplies. Our results suggest that, during normal development, Sima/HIF-1α prevents growth-induced demand from exceeding available supplies, which become increasing scarce as tissue size increases.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE264119 | GEO | 2025/04/16

REPOSITORIES: GEO