Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways

Fangfang Ren, Bing Wang, Tao Yue, Eun Young Yun, Y. Tony Ip, Jin Jiang

Research output: Contribution to journalArticle

199 Scopus citations

Abstract

Intestinal stem cells (ISCs) in the Drosophila adult midgut are essential for maintaining tissue homeostasis and replenishing lost cells in response to tissue damage. Here we demonstrate that the Hippo (Hpo) signaling pathway, an evolutionarily conserved pathway implicated in organ size control and tumorigenesis, plays an essential role in regulating ISC proliferation. Loss of Hpo signaling in either midgut precursor cells or epithelial cells stimulates ISC proliferation. We provide evidence that loss of Hpo signaling in epithelial cells increases the production of cytokines of theUpdfamily and multiple EGFR ligands that activate JAK-STAT and EGFR signaling pathways in ISCs to stimulate their proliferation, thus revealing a unique non- cell-autonomous role of Hpo signaling in blocking ISC proliferation. Finally,we show that the Hpo pathway mediator Yorkie (Yki) is also required in precursor cells for injury-induced ISC proliferation in response to tissue-damaging reagent DSS.

Original languageEnglish (US)
Pages (from-to)21064-21069
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number49
DOIs
StatePublished - Dec 7 2010

Keywords

  • Regeneration
  • Wts
  • Yap

ASJC Scopus subject areas

  • General

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