An EGF-Responsive Neural Circuit Couples Insulin Secretion with Nutrition in Drosophila

Dev Cell. 2019 Jan 7;48(1):76-86.e5. doi: 10.1016/j.devcel.2018.11.029. Epub 2018 Dec 13.

Abstract

Developing organisms use fine-tuning mechanisms to adjust body growth to ever-changing nutritional conditions. In Drosophila, the secretory activity of insulin-producing cells (IPCs) is central to couple systemic growth with amino acids availability. Here, we identify a subpopulation of inhibitory neurons contacting the IPCs (IPC-connecting neurons or ICNs) that play a key role in this coupling. We show that ICNs respond to growth-blocking peptides (GBPs), a family of fat-body-derived signals produced upon availability of dietary amino acids. We demonstrate that GBPs are atypical ligands for the fly EGF receptor (EGFR). Upon activation of EGFR by adipose GBPs, ICN-mediated inhibition of IPC function is relieved, allowing insulin secretion. Our study reveals an unexpected role for EGF-like metabolic hormones and EGFR signaling as critical modulators of neural activity, coupling insulin secretion to the nutritional status.

Keywords: Drosophila; EGF; GBPs; growth; insulin; inter-organ communication; neuronal circuit; nutrition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / metabolism*
  • Epidermal Growth Factor / metabolism*
  • Insulin / metabolism
  • Insulin Secretion / physiology*
  • Insulin-Secreting Cells / metabolism*
  • Larva / metabolism
  • Neurons / metabolism*
  • Nutritional Status / physiology

Substances

  • Drosophila Proteins
  • Insulin
  • Epidermal Growth Factor