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 the Upd family 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.
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Ren
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Yue
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Yun
authors.forename: Y Tony
authors.initials: YT
authors.lastname: Ip
authors.forename: Jin
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D004847:Epithelial Cells; D066246:ErbB Receptors / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D053612:Janus Kinases / Q000378:metabolism; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D018010:Receptors, Invertebrate Peptide / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D016207:Cytokines; D029721:Drosophila Proteins; D066246:ErbB Receptors; D047908:Intracellular Signaling Peptides and Proteins; D053612:Janus Kinases; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D018010:Receptors, Invertebrate Peptide; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; C066532:Egfr protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases