Duox activation in Drosophila Malpighian tubules stimulates intestinal epithelial renewal through a countercurrent flow

Cell Rep. 2024 Apr 23;43(4):114109. doi: 10.1016/j.celrep.2024.114109. Epub 2024 Apr 12.

Abstract

The gut must perform a dual role of protecting the host against toxins and pathogens while harboring mutualistic microbiota. Previous studies suggested that the NADPH oxidase Duox contributes to intestinal homeostasis in Drosophila by producing reactive oxygen species (ROS) in the gut that stimulate epithelial renewal. We find instead that the ROS generated by Duox in the Malpighian tubules leads to the production of Upd3, which enters the gut and stimulates stem cell proliferation. We describe in Drosophila the existence of a countercurrent flow system, which pushes tubule-derived Upd3 to the anterior part of the gut and stimulates epithelial renewal at a distance. Thus, our paper clarifies the role of Duox in gut homeostasis and describes the existence of retrograde fluid flow in the gut, collectively revealing a fascinating example of inter-organ communication.

Keywords: CP: Developmental biology; CP: Immunology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Drosophila / metabolism
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster* / metabolism
  • Dual Oxidases / genetics
  • Dual Oxidases / metabolism
  • Homeostasis
  • Intestinal Mucosa* / metabolism
  • Malpighian Tubules* / metabolism
  • NADPH Oxidases / metabolism
  • Reactive Oxygen Species* / metabolism

Substances

  • Drosophila Proteins
  • Reactive Oxygen Species
  • NADPH Oxidases
  • dual oxidase, Drosophila
  • Dual Oxidases
  • Upd3 protein, Drosophila