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Science 326 (5958): 1403-1405

Copyright © 2009 by the American Association for the Advancement of Science

The Insect Neuropeptide PTTH Activates Receptor Tyrosine Kinase Torso to Initiate Metamorphosis

Kim F. Rewitz,1 Naoki Yamanaka,1,2 Lawrence I. Gilbert,3 Michael B. O’Connor1,2,*

Abstract: Holometabolous insects undergo complete metamorphosis to become sexually mature adults. Metamorphosis is initiated by brain-derived prothoracicotropic hormone (PTTH), which stimulates the production of the molting hormone ecdysone via an incompletely defined signaling pathway. Here we demonstrate that Torso, a receptor tyrosine kinase that regulates embryonic terminal cell fate in Drosophila, is the PTTH receptor. Trunk, the embryonic Torso ligand, is related to PTTH, and ectopic expression of PTTH in the embryo partially rescues trunk mutants. In larvae, torso is expressed specifically in the prothoracic gland (PG), and its loss phenocopies the removal of PTTH. The activation of Torso by PTTH stimulates extracellular signal–regulated kinase (ERK) phosphorylation, and the loss of ERK in the PG phenocopies the loss of PTTH and Torso. We conclude that PTTH initiates metamorphosis by activation of the Torso/ERK pathway.

1 Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
2 Howard Hughes Medical Institute, University of Minnesota, Minneapolis, MN 55455, USA.
3 Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.

* To whom correspondence should be addressed. E-mail: moconnor{at}umn.edu


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