Data from: Nutritional control of body size through FoxO-Ultraspiracle mediated ecdysone biosynthesis

Despite their fundamental importance for body size regulation, the
mechanisms that stop growth are poorly understood. In Drosophila
melanogaster, growth ceases in response to a peak of the molting hormone
ecdysone that coincides with a nutrition-dependent checkpoint, critical
weight. Previous studies indicate that insulin/insulin-like growth factor
signaling (IIS)/Target of Rapamycin (TOR) signaling in the prothoracic
glands (PGs) regulates ecdysone biosynthesis and critical weight. Here we
elucidate a mechanism through which this occurs. We show that Forkhead Box
class O (FoxO), a negative regulator of IIS/TOR, directly interacts with
Ultraspiracle (Usp), part of the ecdysone receptor. While overexpressing
FoxO in the PGs delays ecdysone biosynthesis and critical weight,
disrupting FoxO–Usp binding reduces these delays. Further, feeding
ecdysone to larvae eliminates the effects of critical weight. Thus,
nutrition controls ecdysone biosynthesis partially via FoxO–Usp prior to
critical weight, ensuring that growth only stops once larvae have achieved
a target nutritional status.