Holometabolous insects undergo a complete transformation from the larval feeding stage into the reproductive adult, and this metamorphosis is regulated by both environmental factors and internal cues. Metamorphosis in the fruit fly Drosophila melanogaster is triggered when prothoracicotropic hormone (PTTH) produced by the brain and perceived by the prothoracic gland (PG) elicits production of the steroid hormone 20-hydroxyecdysone (20E), the systemic signal that induces physiological and behavioral changes. Although this sequence of events has been known for decades, the molecular machinery linking PTTH to 20E production has been unclear. Rewitz et al. report that PTTH acts through the tyrosine kinase receptor Torso, which also serves as the receptor for Trunk (Trk), a neuropeptide structurally similar to PTTH that is required during embroygenesis but not present in late larvae. Reducing Torso in the PG by tissue-specific RNA interference (RNAi) produced a delayed pupariation phenotype characterized by a prolonged final larval stage and abnormally large pupae. This phenotype was virtually identical to that in animals lacking PTTH and could be prevented by feeding 20E to the torso RNAi animals. Ubiquitous expression of a transgene encoding PTTH or a constitutively active form of Torso caused premature pupariation and small pupae. Although PTTH is not normally present in embryos, ectopic expression of a transgene encoding PTTH in trk mutant embryos partially rescued Trk-dependent gene expression and formation of posterior structures, indicating that PTTH could activate signaling through Torso in the embryo. Because Trk binding to Torso activates the mitogen-activated protein kinase (MAPK) signaling cascade in the embryo, the authors tested whether PTTH binding to Torso also activated MAPK in the larval PG. RNAi of the MAPK ERK prolonged the late larval growth period and delayed pupariation, and feeding 20E to these animals prevented the RNAi phenotype. Stimulating cultured Drosophila cells with PTTH resulted in ERK phosphorylation, an indication of MAPK pathway activation. Thus, PTTH binding to Torso leads to production of 20E through activation of a MAPK cascade.
K. F. Rewitz, N. Yamanaka, L. I. Gilbert, M. B. O’Connor, The insect neuropeptide PTTH activates receptor tyrosine kinase Torso to initiate metamorphosis. Science 326, 1403–1405 (2009). [Abstract] [Full Text]