title: EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila.
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.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA.
authors.forename: Huaqi
authors.initials: H
authors.lastname: Jiang
authors.forename: Marc O
authors.initials: MO
authors.lastname: Grenley
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Bravo
authors.forename: Rachel Z
authors.initials: RZ
authors.lastname: Blumhagen
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Edgar
mesh_terms: D000818:Animals; D017849:Animals, Inbred Strains; D049109:Cell Proliferation; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006706:Homeostasis; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D053612:Janus Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D018010:Receptors, Invertebrate Peptide / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D018010:Receptors, Invertebrate Peptide; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D053612:Janus Kinases; D018631:ras Proteins