Dynamic feedback shapes steroid pulses in Drosophila. Morten E. Møller¹, E. Thomas Danielsen¹, Rachel Harder², Michael B. OConner², Kim F. Rewitz¹. 1) Department of Biology, University of Copenhagen, Copenhagen, Denmark; 2) Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota.

   Pulses of steroid hormones act as temporal signals that drive the juvenile-adult transition, which transforms the developing organism to a reproductively mature adult. This transition, known as metamorphosis in Drosophila, is triggered by pulses of the steroid hormone ecdysone produced and released from the prothoracic gland (PG). Ecdysone is synthesized in response to prothoracicotropic hormone (PTTH) release from the brain through a series of enzymatic reactions mediated by P450 enzymes. Although PTTH stimulates ecdysone synthesis, that alone cannot account for mechanisms determining the duration of the pulse. We show an ecdysone-dependent feedback switch in the PG which is required for the rapid increase and following decline of the ecdysone titer. This switch consists of a feedforward and a feedback loop. Blocking the feedforward loop in the PG results in reduced levels of ecdysone and delayed puparation. The negative feedback is responsible for the following decline of the titer, together these processes are required for generating a pulse that drives developmental progression. The feedback is mediated through the ecdysone receptor (EcR) that induces the expression of a transcription factor called Broad, which regulates the expression of the ecdysone biosynthetic enzymes by binding onto their promoters. Different Broad isoforms are responsible for the transcriptional activation and repression that changes the capacity of the PG to produce ecdysone. In conclusion: These findings demonstrate a feedback mechanism in the PG involving EcR and Broad, which is required to establishes the temporal boundaries of the ecdysone pulse and developmental transition to adulthood.