Feedforward Regulation of Glucose Metabolism by Steroid Hormones Drives a Developmental Transition in Drosophila

Abstract

Metabolism must be coupled with developmental transition to fulfill the energy requirements during an organism's life cycle. In most animals, steroid hormones are crucial regulators of life-stage transitions until adulthood. In the fruit fly Drosophila, ecdysteroid titers drive developmental transitions, such as molting and metamorphosis [1-4]. Although the timings of molting and larval-pupal transition are dependent on environmental and internal conditions, metamorphosis is a temporally controlled life transition event that solely relies on energetic macromolecules accumulated during the larval period. The ecdysteroid signaling cascade and the energetics of metamorphosis have been determined [5-8]. However, the molecular mechanisms that regulate metabolic homeostasis during metamorphosis remain largely unknown. Here, I show that the programmed regulation of carbohydrate metabolism by steroid hormones directs the prepupal-pupal transition in Drosophila. I found that pupation is associated with a transient increase in glucose oxidation. Mechanistically, after pupariation, ecdysteroid signaling and the competence factor Ftz-F1 regulates the systematic degradation of circulating trehalose via the transient induction of trehalose transporters and trehalase (Treh) in a timely manner. Trehalose metabolism is crucial for energy homeostasis at the prepupal-pupal transition. Moreover, trehalose catabolism acts upstream of ecdysteroid biosynthesis and signaling. My findings lead to the hypothesis that trehalose breakdown not only defines energy costs by providing a carbon source but also facilitates pupation by inducing water loss in the puparium. My work sheds light on the ways in which a life-stage transition is driven by the preprogrammed coordination between steroid hormones and catabolism of stored nutrients.