At the onset of the L3 (left), IIS/TOR signaling is reduced in the PG cells and the FoxO/Usp complex suppresses ecdysone biosynthesis either directly, as drawn, or indirectly. As the larvae feed, FoxO becomes phosphorylated and transported out of the nucleus, thereby dissociating FoxO/Usp complexes. As a result, ecdysone biosynthesis becomes derepressed (upper right). After critical weight, ecdysone reduces its own biosynthesis through a negative-feedback loop. In starved conditions, the IIS/TOR signaling activity in the PGs remains low, thereby unphosphorylated FoxO remains inside of nuclei forming complexes with Usp (lower right). This inhibits ecdysone biosynthetic gene expression, thereby repressing ecdysone biosynthesis and delaying metamorphosis. FoxO on its own or with an unknown partner(s) may also regulate ecdysone biosynthesis.