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
AU - Edgar, Bruce A.
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.
UR - http://europepmc.org/articles/PMC2753793
U2 - 10.1016/j.cell.2009.05.014
DO - 10.1016/j.cell.2009.05.014
M3 - Article (Academic Journal)
C2 - 19563763
SN - 0092-8674
VL - 137
SP - 1343
EP - 1355
JO - Cell
JF - Cell
IS - 7
ER -