Developmental transitions are often triggered by a neuroendocrine axis and can be contingent upon multiple organs achieving sufficient growth and maturation. How the neurodendocrine axis senses the size and maturity of peripheral organs is not known. In Drosophila larvae, metamorphosis is triggered by a sharp increase in the level of the steroid hormone ecdysone, secreted by the prothoracic gland (PG). Here, we show that the BMP2/4 ortholog Dpp can function as a systemic signal to regulate developmental timing. Dpp from peripheral tissues, mostly imaginal discs, can reach the PG and inhibit ecdysone biosynthesis. As the discs grow, reduced Dpp signaling in the PG is observed, consistent with the possibility that Dpp functions in a checkpoint mechanism that prevents metamorphosis when growth is insufficient. Indeed, upon starvation early in the third larval instar, reducing Dpp signaling in the PG abrogates the critical-weight checkpoint which normally prevents pupariation under these conditions. We suggest that increased local trapping of morphogen within tissues as they grow would reduce circulating levels and hence provide a systemic readout of their growth status.
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We thank many colleagues in the fly community for constructive suggestions; María Domínguez, Marcos González-Gaitán, Pierre Léopold, Michael O’Connor, Lynn Riddiford, Chris Rushlow, Michael Thomas Marr, Hilary Ashe, Jean-Paul Vincent, Markus Affolter, and Konrad Basler for fly stocks and antibodies; the Bloomington, VDRC and TRiP stock centers; Octavio Bejarano, Jane Thomas, and Lupita Hernandez for technical assistance; and Jo Downes Bairzin, David Bilder, Robin Harris, Nipam Patel, Taryn Sumabat, and Melanie Worley for comments on the manuscript. IK Hariharan was funded by National Institutes of Health (NIH) grant R35GM122490 and an American Cancer Society Research Professor Award (RP-16-238-06-COUN). MB O’Connor was funded by NIH grant R35GM118029.
© 2018 Setiawan et al.
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