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

• Autor(a) principal: Koyama, Takashi
• Data de Publicação: 2014
• Outros Autores: Rodrigues, Marisa A, Athanasiadis, Alekos, Shingleton, Alexander W, Mirth, Christen K
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.7/491
• topic: D. melanogaster; body size; critical weight; developmental biology; ecdysone; insulin/insulin-like growth factor; nutrition-dependent signaling; stem cells; target of rapamycin

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.