Ecdysone promotes growth of imaginal discs through the regulation of Thor in D. melanogaster

Animals have a determined species-specific body size that results from the combined action of hormones and signaling pathways regulating growth rate and duration. In Drosophila, the steroid hormone ecdysone controls developmental transitions, thereby regulating the duration of the growth period. Here we show that ecdysone promotes the growth of imaginal discs in mid-third instar larvae, since imaginal discs from larvae with reduced or no ecdysone synthesis are smaller than wild type due to smaller and fewer cells. We show that insulin-like peptides are produced and secreted normally in larvae with reduced ecdysone synthesis, and upstream components of insulin/insulin-like signaling are activated in their discs. Instead, ecdysone appears to regulate the growth of imaginal discs via Thor/4E-BP, a negative growth regulator downstream of the insulin/insulin-like growth factor/Tor pathways. Discs from larvae with reduced ecdysone synthesis have elevated levels of Thor, while mutations in Thor partially rescue their growth. The regulation of organ growth by ecdysone is evolutionarily conserved in hemimetabolous insects, as shown by our results obtained using Blattella germanica. In summary, our data provide new insights into the relationship between components of the insulin/insulin-like/Tor and ecdysone pathways in the control of organ growth.Spanish Ministry of Science and Consolider program grants: (BFU-2008-01884, BFU2011-25986, CSD2007-008-25120, BFU2009-10571 and BES-2009-016077); Departments of Education and Industry of the Basque Government grant: (PI2012/42); Bizkaia County; Instituto Gulbenkian de Ciência/Fundação Calouste Gulbenkian; Fundação Para a Ciência e a Tecnologia fellowship: (SFRH/BD/51181/2010)