Starvation induces FoxO-dependent mitotic-to-endocycle switch pausing during Drosophila oogenesis

Abstract

When exposed to nutrient challenge, organisms have to adapt their physiology in order to balance reproduction with adult fitness. In mammals, ovarian follicles enter a massive growth phase during which they become highly dependent on gonadotrophic factors and nutrients. Somatic tissues play a crucial role in integrating these signals, controlling ovarian follicle atresia and eventually leading to the selection of a single follicle for ovulation. We used Drosophila follicles as a model to study the effect of starvation on follicle maturation. Upon starvation, Drosophila vitellogenic follicles adopt an 'atresia-like' behavior, in which some slow down their development whereas others enter degeneration. The mitotic-to-endocycle (M/E) transition is a critical step during Drosophila oogenesis, allowing the entry of egg chambers into vitellogenesis. Here, we describe a specific and transient phase during M/E switching that is paused upon starvation. The Insulin pathway induces the pausing of the M/E switch, blocking the entry of egg chambers into vitellogenesis. Pausing of the M/E switch involves a previously unknown crosstalk between FoxO, Cut and Notch that ensures full reversion of the process and rapid resumption of oogenesis upon refeeding. Our work reveals a novel genetic mechanism controlling the extent of the M/E switch upon starvation, thus integrating metabolic cues with development, growth and reproduction.