Nutritional control of body size through FoxO-Ultraspiracle mediated ecdysone biosynthesis

Elife. 2014 Nov 25;3:e03091. doi: 10.7554/eLife.03091.

Abstract

Despite their fundamental importance for body size regulation, the mechanisms that stop growth are poorly understood. In Drosophila melanogaster, growth ceases in response to a peak of the molting hormone ecdysone that coincides with a nutrition-dependent checkpoint, critical weight. Previous studies indicate that insulin/insulin-like growth factor signaling (IIS)/Target of Rapamycin (TOR) signaling in the prothoracic glands (PGs) regulates ecdysone biosynthesis and critical weight. Here we elucidate a mechanism through which this occurs. We show that Forkhead Box class O (FoxO), a negative regulator of IIS/TOR, directly interacts with Ultraspiracle (Usp), part of the ecdysone receptor. While overexpressing FoxO in the PGs delays ecdysone biosynthesis and critical weight, disrupting FoxO-Usp binding reduces these delays. Further, feeding ecdysone to larvae eliminates the effects of critical weight. Thus, nutrition controls ecdysone biosynthesis partially via FoxO-Usp prior to critical weight, ensuring that growth only stops once larvae have achieved a target nutritional status.

Keywords: D. melanogaster; body size; critical weight; developmental biology; ecdysone; insulin/insulin-like growth factor; nutrition-dependent signaling; stem cells; target of rapamycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animal Nutritional Physiological Phenomena*
  • Animal Structures / metabolism
  • Animals
  • Binding Sites
  • Body Size* / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / anatomy & histology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Ecdysone / biosynthesis*
  • Feeding Behavior
  • Forkhead Transcription Factors / chemistry
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Developmental
  • Insulin / metabolism
  • Larva / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Protein Binding
  • Signal Transduction
  • Somatomedins / metabolism
  • Starvation
  • Time Factors
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • FOXO protein, Drosophila
  • Forkhead Transcription Factors
  • Insulin
  • Somatomedins
  • Transcription Factors
  • USP protein, Drosophila
  • Ecdysone

Associated data

  • Dryad/10.5061/dryad.75940

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.