The role of FoxO in integrating insulin and ecdysone signaling during body size regulation. Takashi Koyama, Christen Mirth. Instituto Gulbenkian de Ciência, Oeiras, Portugal.

   Body size regulation, a conspicuous and fundamental process in any organism, is best understood in insects. In the fruit fly Drosophila melanogaster, larvae regulate their final body size by controlling both growth rate, through insulin/insulin-like growth factor signaling (IIS) and target of rapamycin signaling, and regulating the duration of the growth period, via the steroid hormone ecdysone. Recent studies have shown that these two processes interact; IIS stimulates ecdysone synthesis from the prothoracic gland by up-regulating ecdysone biosynthesis genes. How this occurs is still unclear. In mammalian and nematode cells, the IIS modulates steroid hormone signaling through the interaction between a downstream component of the IIS, forkhead box type O (FoxO), and nuclear hormone receptor superfamily members. Given this, we have found that a heterodimeric partner of Ecdysone Receptor, Ultraspiracle (Usp), binds to FoxO. Furthermore, we found that overexpression of FoxO RNAi in the prothoracic gland (PG) induces premature patterning of the imaginal discs in early third instar larvae fed on sucrose alone, suggesting ecdysone synthesis occurs prematurely. This FoxO/Usp association occurs independently of 20-hydroxyecdysone, suggesting that the complex may potentially regulate ecdysone signaling in a nutrient-dependent, but ecdysone-independent manner. To explore the function of FoxO/Usp complex, we have created two different types of transgenes that alter the state of FoxO/Usp complexes without disrupting independent transcriptional activity of FoxO. We will discuss about the function of the FoxO/Usp complex on growth period determination.