Ecdysone-dependent feedback regulation of prothoracicotropic hormone controls the timing of developmental maturation

Development. 2020 Jul 24;147(14):dev188110. doi: 10.1242/dev.188110.

Abstract

The activation of a neuroendocrine system that induces a surge in steroid production is a conserved initiator of the juvenile-to-adult transition in many animals. The trigger for maturation is the secretion of brain-derived neuropeptides, yet the mechanisms controlling the timely onset of this event remain ill-defined. Here, we show that a regulatory feedback circuit controlling the Drosophila neuropeptide Prothoracicotropic hormone (PTTH) triggers maturation onset. We identify the Ecdysone Receptor (EcR) in the PTTH-expressing neurons (PTTHn) as a regulator of developmental maturation onset. Loss of EcR in these PTTHn impairs PTTH signaling, which delays maturation. We find that the steroid ecdysone dose-dependently affects Ptth transcription, promoting its expression at lower concentrations and inhibiting it at higher concentrations. Our findings indicate the existence of a feedback circuit in which rising ecdysone levels trigger, via EcR activity in the PTTHn, the PTTH surge that generates the maturation-inducing ecdysone peak toward the end of larval development. Because steroid feedback is also known to control the vertebrate maturation-inducing hypothalamic-pituitary-gonadal axis, our findings suggest an overall conservation of the feedback-regulatory neuroendocrine circuitry that controls the timing of maturation initiation.

Keywords: Drosophila; Ecdysone; Maturation; Prothoracicotropic; Ptth; Steroid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Size
  • Drosophila / growth & development
  • Drosophila / metabolism
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Ecdysterone / pharmacology
  • Gene Expression Regulation, Developmental / drug effects
  • Insect Hormones / antagonists & inhibitors
  • Insect Hormones / genetics
  • Insect Hormones / metabolism*
  • Larva / growth & development
  • Larva / metabolism
  • Metamorphosis, Biological
  • Microscopy, Fluorescence
  • Neurons / metabolism
  • RNA Interference
  • RNA, Guide, CRISPR-Cas Systems
  • Receptors, Steroid / antagonists & inhibitors
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism*
  • Signal Transduction

Substances

  • Drosophila Proteins
  • Insect Hormones
  • Receptors, Steroid
  • ecdysone receptor
  • Ecdysterone
  • prothoracicotropic hormone