TY - JOUR
T1 - Cytokine/Jak/Stat Signaling Mediates Regeneration and Homeostasis in the Drosophila Midgut
AU - Jiang, Huaqi
AU - Patel, Parthive H.
AU - Kohlmaier, Alexander
AU - Grenley, Marc O.
AU - McEwen, Donald G.
AU - Edgar, Bruce A.
N1 - Funding Information:
We thank G. Schubiger, C. O'Cane, N. Reich, P. Hagan, D. Montell, G. Baeg, P. O'Farrell, M. Van Doren, E. Bach, K. Choi, S. Hou, H. Sun, K. Smith, VDRC, NIG, and the Bloomington DSC for reagents. We thank C. M. Ulrich for comments on the manuscript. This work was supported by the UW/FHCRC Cancer Consortium and National Institutes of Health grant R01 GM51186 to B.A.E. P.H.P. was an American Cancer Society Fellow (PF-08-040-01-DDC). A.K. was a Human Frontiers in Science Program Fellow.
PY - 2009/6/26
Y1 - 2009/6/26
N2 - 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.
AB - 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.
KW - DEVBIO
UR - http://www.scopus.com/inward/record.url?scp=67549133157&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67549133157&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2009.05.014
DO - 10.1016/j.cell.2009.05.014
M3 - Article
C2 - 19563763
AN - SCOPUS:67549133157
SN - 0092-8674
VL - 137
SP - 1343
EP - 1355
JO - Cell
JF - Cell
IS - 7
ER -