NAD⁺ supply and redox state limit developmental speed in the Drosophila eye

The cellular and biochemical processes that define the speed at which embryos develop, tissues form, and cells differentiate remain largely unknown. Using the speed of progression of a differentiation front in the developing Drosophila eye to measure developmental speed, we identified genetic perturbations that slowed the progression of this front. Inhibiting the electron transport chain (ETC), and more generally energy production in mitochondria, resulted in reduced developmental speed. Defective ETC activity led to increased NADH/NAD⁺ ratio, whereas ATP levels remained constant due to a compensatory increase in glycolysis. Targeted perturbations showed that the metabolic state of the cells ahead of and/or at the differentiation front determined its speed. Genetic and diet-based perturbations of NAD⁺ metabolism indicated that developmental speed was limited by NAD⁺ availability. Thus, developmental speed appeared constrained by the cellular redox state and the demand for NAD⁺ in the developing Drosophila eye. Our findings therefore show that the NADH/NAD⁺ ratio is key to regulating developmental speed and highlight the importance of NAD⁺ availability for this regulation in Drosophila.