In insects, control of body size is intimately linked to nutritional quality as well as environmental and genetic cues that regulate the timing of developmental transitions. Prothoracicotropic hormone (PTTH) has been proposed to play an essential role in regulating the production and/or release of ecdysone, a steroid hormone that stimulates molting and metamorphosis. In this report, we examine the consequences on Drosophila development of ablating the PTTH-producing neurons. Surprisingly, PTTH production is not essential for molting or metamorphosis. Instead, loss of PTTH results in delayed larval development and eclosion of larger flies with more cells. Prolonged feeding, without changing the rate of growth, causes the overgrowth and is a consequence of low ecdysteroid titers. These results indicate that final body size in insects is determined by a balance between growth-rate regulators such as insulin and developmental timing cues such as PTTH that set the duration of the feeding interval.
Bibliographical noteFunding Information:
We thank members of the M.B.O. lab for comments on the manuscript, Paul Taghert for pdf mutant flies and antibody, and John Nambu for the UAS-Grim lines. We are grateful to Changqi Zhu for dissection and photographs of PTTH expression in adult brains and A. Hadfi for his help on synchronizing larvae. R.B.B. was supported by a National Institutes of Health (NIH) Multidisciplinary Cancer Research Training Program (T32 CA0093247). C.S.T. was supported by a grant from the NIH (R01 DK075607). L.I.G. and J.T.W. were supported by National Science Foundation grant 1BN0130825. J.-P.P. and C.D.-V. are supported by the Université Pierre et Marie Curie and the Centre National de la Recherche Scientifique. M.B.O. is an investigator with the Howard Hughes Medical Institute.