EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in drosophila

Huaqi Jiang, Marc O. Grenley, Maria Jose Bravo, Rachel Z. Blumhagen, Bruce A. Edgar

Research output: Contribution to journalArticle

262 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)84-95
Number of pages12
JournalCell Stem Cell
Volume8
Issue number1
DOIs
StatePublished - Jan 7 2011

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ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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