RRC ID 11060
Author Jiang H, Grenley MO, Bravo MJ, Blumhagen RZ, Edgar BA.
Title EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila.
Journal Cell Stem Cell
Abstract Many tissues in higher animals undergo dynamic homeostatic growth, wherein damaged or aged cells are replaced by the progeny of resident stem cells. To maintain homeostasis, stem cells must respond to tissue needs. Here we show that in response to damage or stress in the intestinal (midgut) epithelium of adult Drosophila, multiple EGFR ligands and rhomboids (intramembrane proteases that activate some EGFR ligands) are induced, leading to the activation of EGFR signaling in intestinal stem cells (ISCs). Activation of EGFR signaling promotes ISC division and midgut epithelium regeneration, thereby maintaining tissue homeostasis. ISCs defective in EGFR signaling cannot grow or divide, are poorly maintained, and cannot support midgut epithelium regeneration after enteric infection by the bacterium Pseudomonas entomophila. Furthermore, ISC proliferation induced by Jak/Stat signaling is dependent upon EGFR signaling. Thus the EGFR/Ras/MAPK signaling pathway plays central, essential roles in ISC maintenance and the feedback system that mediates intestinal homeostasis.
Volume 8(1)
Pages 84-95
Published 2011-1-7
DOI 10.1016/j.stem.2010.11.026
PII S1934-5909(10)00648-X
PMID 21167805
PMC PMC3021119
MeSH Animals Animals, Inbred Strains Cell Proliferation Drosophila / physiology* Drosophila Proteins / metabolism* Epithelial Cells / cytology Epithelial Cells / metabolism Homeostasis Intestinal Mucosa / enzymology Intestinal Mucosa / metabolism Intestinal Mucosa / physiology* Intestines / metabolism Janus Kinases / metabolism MAP Kinase Signaling System / physiology* Receptor, Epidermal Growth Factor / metabolism* Receptors, Invertebrate Peptide / metabolism* Regeneration / physiology* Stem Cells / cytology Stem Cells / enzymology Stem Cells / metabolism* ras Proteins / metabolism*
IF 21.464
Times Cited 163