Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut.
Cells in intestinal epithelia turn over rapidly due to damage from digestion and toxins produced by the enteric microbiota. Gut homeostasis is maintained by intestinal stem cells (ISCs) that divide to replenish the intestinal epithelium, but little is known about how ISC division and differentiation are coordinated with epithelial cell loss. We show here that when enterocytes (ECs) in the Drosophila midgut are subjected to apoptosis, enteric infection, or JNK-mediated stress signaling, they produce cytokines (Upd, Upd2, and Upd3) that activate Jak/Stat signaling in ISCs, promoting their rapid division. Upd/Jak/Stat activity also promotes progenitor cell differentiation, in part by stimulating Delta/Notch signaling, and is required for differentiation in both normal and regenerating midguts. Hence, cytokine-mediated feedback enables stem cells to replace spent progeny as they are lost, thereby establishing gut homeostasis.
Jiang
Huaqi
H
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
Patel
Parthive H
PH
Kohlmaier
Alexander
A
Grenley
Marc O
MO
McEwen
Donald G
DG
Edgar
Bruce A
BA
D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism; D004330:Drosophila / Q000166:cytology* / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D029721:Drosophila Proteins / Q000378:metabolism; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism; D006706:Homeostasis; D007422:Intestines / Q000166:cytology / Q000382:microbiology / Q000502:physiology; D053612:Janus Kinases / Q000378:metabolism; D012038:Regeneration; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D016207:Cytokines; D029721:Drosophila Proteins; D050791:STAT Transcription Factors; D014157:Transcription Factors; D053612:Janus Kinases; C085845:hop protein, Drosophila