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

184 Citations (Scopus)

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

Fingerprint

Drosophila
Intestines
Stem Cells
Cell Proliferation
Epithelial Cells
Organ Size
Carcinogenesis
Homeostasis
Cytokines
Ligands
Wounds and Injuries

Keywords

  • Regeneration
  • Wts
  • Yap

ASJC Scopus subject areas

  • General

Cite this

Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways. / Ren, Fangfang; Wang, Bing; Yue, Tao; Yun, Eun Young; Ip, Y. Tony; Jiang, Jin.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 49, 07.12.2010, p. 21064-21069.

Research output: Contribution to journalArticle

@article{8baa2fccfd7a4cb89a64b1350c01ae90,
title = "Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways",
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.",
keywords = "Regeneration, Wts, Yap",
author = "Fangfang Ren and Bing Wang and Tao Yue and Yun, {Eun Young} and Ip, {Y. Tony} and Jin Jiang",
year = "2010",
month = "12",
day = "7",
doi = "10.1073/pnas.1012759107",
language = "English (US)",
volume = "107",
pages = "21064--21069",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "49",

}

TY - JOUR

T1 - Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways

AU - Ren, Fangfang

AU - Wang, Bing

AU - Yue, Tao

AU - Yun, Eun Young

AU - Ip, Y. Tony

AU - Jiang, Jin

PY - 2010/12/7

Y1 - 2010/12/7

N2 - 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.

AB - 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.

KW - Regeneration

KW - Wts

KW - Yap

UR - http://www.scopus.com/inward/record.url?scp=78650471357&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650471357&partnerID=8YFLogxK

U2 - 10.1073/pnas.1012759107

DO - 10.1073/pnas.1012759107

M3 - Article

C2 - 21078993

AN - SCOPUS:78650471357

VL - 107

SP - 21064

EP - 21069

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 49

ER -