Dynamic feedback circuits function as a switch for shaping a maturation-inducing steroid pulse in Drosophila

Morten E. Moeller, E. Thomas Danielsen, Rachel Herder, Michael B. O'Connor, Kim F. Rewitz*

*Corresponding author

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Steroid hormones trigger the onset of sexual maturation in animals by initiating genetic response programs that are determined by steroid pulse frequency, amplitude and duration. Although steroid pulses coordinate growth and timing of maturation during development, the mechanisms generating these pulses are not known. Here we show that the ecdysone steroid pulse that drives the juvenile-adult transition in Drosophila is determined by feedback circuits in the prothoracic gland (PG), the major steroid-producing tissue of insect larvae. These circuits coordinate the activation and repression of hormone synthesis, the two key parameters determining pulse shape (amplitude and duration). We show that ecdysone has a positive-feedback effect on the PG, rapidly amplifying its own synthesis to trigger pupariation as the onset of maturation. During the prepupal stage, a negative-feedback signal ensures the decline in ecdysone levels required to produce a temporal steroid pulse that drives developmental progression to adulthood. The feedback circuits rely on a developmental switch in the expression of Broad isoforms that transcriptionally activate or silence components in the ecdysone biosynthetic pathway. Remarkably, our study shows that the same well-defined genetic program that stimulates a systemic downstream response to ecdysone is also utilized upstream to set the duration and amplitude of the ecdysone pulse. Activation of this switch-like mechanism ensures a rapid, self-limiting PG response that functions in producing steroid oscillations that can guide the decision to terminate growth and promote maturation.
Original languageEnglish
JournalDevelopment
Volume140
Issue number23
Pages (from-to)4730-4739
Number of pages10
ISSN1011-6370
DOIs
Publication statusPublished - 2013
Externally publishedYes

Bibliographical note

This work was supported by the Danish Council for Independent Research,Natural Sciences [grant 11-105446 to K.F.R.] and the National Institutes of Health[grant R01 GM093301 to M.B.O.].

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