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.尽管生长终止机制对于体型调控具有核心重要性，但目前学界对其仍不甚明晰。在黑腹果蝇（Drosophila melanogaster）中，幼虫生长会在蜕皮激素（ecdysone）峰值触发下终止，该激素峰值与依赖营养的检查点——临界体重（critical weight）同步出现。既往研究表明，前胸腺（prothoracic glands, PGs）内的胰岛素/胰岛素样生长因子信号（insulin/insulin-like growth factor signaling, IIS）/雷帕霉素靶蛋白（Target of Rapamycin, TOR）信号通路，可调控蜕皮激素的生物合成与临界体重的相关进程。本研究阐明了该调控过程的一项分子机制：我们发现，作为IIS/TOR通路负调控因子的叉头框O类蛋白（Forkhead Box class O, FoxO），可直接与蜕皮激素受体（ecdysone receptor）的组成组分超螺旋蛋白（Ultraspiracle, Usp）发生相互作用。在胸腺中过表达FoxO会延迟蜕皮激素的生物合成与临界体重的出现，而破坏FoxO与Usp的结合则可削弱这种延迟效应。进一步实验显示，向幼虫饲喂蜕皮激素可消除临界体重带来的相关影响。综上，在临界体重出现前，营养信号可通过FoxO-Usp通路部分调控蜕皮激素的生物合成，从而确保幼虫仅在达到目标营养状态后才终止生长。