Muscle niche-driven Insulin-Notch-Myc cascade reactivates dormant Adult Muscle Precursors in Drosophila

Elife. 2015 Dec 9;4:e08497. doi: 10.7554/eLife.08497.

Abstract

How stem cells specified during development keep their non-differentiated quiescent state, and how they are reactivated, remain poorly understood. Here, we applied a Drosophila model to follow in vivo behavior of adult muscle precursors (AMPs), the transient fruit fly muscle stem cells. We report that emerging AMPs send out thin filopodia that make contact with neighboring muscles. AMPs keep their filopodia-based association with muscles throughout their dormant state but also when they start to proliferate, suggesting that muscles could play a role in AMP reactivation. Indeed, our genetic analyses indicate that muscles send inductive dIlp6 signals that switch the Insulin pathway ON in closely associated AMPs. This leads to the activation of Notch, which regulates AMP proliferation via dMyc. Altogether, we report that Drosophila AMPs display homing behavior to muscle niche and that the niche-driven Insulin-Notch-dMyc cascade plays a key role in setting the activated state of AMPs.

Keywords: D. melanogaster; Drosophila; Insulin; Notch; developmental biology; muscle niche; muscle stem cell; quiescence; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / metabolism*
  • Drosophila*
  • Insulin / metabolism*
  • Muscles / physiology
  • Myoblasts / drug effects*
  • Myoblasts / physiology*
  • Receptors, Notch / metabolism*
  • Signal Transduction*
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Insulin
  • Myc protein, Drosophila
  • N protein, Drosophila
  • Receptors, Notch
  • Transcription Factors

Grant support

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