Damage sensing by a Nox-Ask1-MKK3-p38 signaling pathway mediates regeneration in the adult Drosophila midgut

Parthive H. Patel, Clothilde Pénalva, Michael Kardorff, Marianne Roca, Bojana Pavlović, Anja Thiel, Aurelio A. Teleman, Bruce A. Edgar

Research output: Contribution to journalArticle (Academic Journal)peer-review

10 Citations (Scopus)
242 Downloads (Pure)

Abstract

Epithelia are exposed to diverse types of stress and damage from pathogens and the environment, and respond by regenerating. Yet, the proximal mechanisms that sense epithelial damage remain poorly understood. Here we report that p38 signaling is activated in adult Drosophila midgut enterocytes in response to diverse stresses including pathogenic bacterial infection and chemical and mechanical insult. Two upstream kinases, Ask1 and Licorne (MKK3), are required for p38 activation following infection, oxidative stress, detergent exposure and wounding. Ask1-p38 signaling in enterocytes is required upon infection to promote full intestinal stem cell (ISC) activation and regeneration, partly through Upd3/Jak-Stat signaling. Furthermore, reactive oxygen species (ROS) produced by the NADPH oxidase Nox in enterocytes, are required for p38 activation in enterocytes following infection or wounding, and for ISC activation upon infection or detergent exposure. We propose that Nox-ROS-Ask1-MKK3-p38 signaling in enterocytes integrates multiple different stresses to induce regeneration.
Original languageEnglish
Article number4365 (2019)
Number of pages14
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 25 Sep 2019

Keywords

  • intestinal stem cells
  • multipotent stem cells
  • regeneration
  • stem-cell niche
  • stress signalling

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