Cellular NAD+ availability constrains developmental speed in the Drosophila eye
The cellular and biochemical processes that limit the rates at which embryos develop, tissues form, and cells differentiate remain largely unknown. Using the speed of progression of a differentiation front in the developing eye of Drosophila as a proxy for developmental speed, we identified genetic perturbations that slowed down the progression of this front. We found that inhibition of the Electron Transport Chain (ETC), and more generally of energy production in mitochondria, reduced developmental speed, led to increased NADH/ NAD+ ratio but did not change ATP levels due to a compensatory increase in glycolysis. Using targeted perturbations, we further showed that the metabolic state of cells located at and ahead of the differentiation front determined the speed of this front. Additionally, increasing the rate of regeneration of the NAD+ pool suppressed the defects resulting from the inhibition of the ETC whereas inhibition of the NAD+ salvage pathway led to reduced developmental speed. Thus, developmental speed appeared to be limited by the demand for NAD+, at least upon reduced energy supply. Overall design: A mirr-Gal4 driver was used to direct gene-based perturbation in the eye imaginal disc. Here, brain complexes from control OreR larvae were compared with those from mirr-Gal4 UAS-ND-42RNAi (BL-28894) larvae (grown at 25°C).