title: Scalloped and Yorkie are required for cell cycle re-entry of quiescent cells after tissue damage.
abstract: Regeneration of damaged tissues typically requires a population of active stem cells. How damaged tissue is regenerated in quiescent tissues lacking a stem cell population is less well understood. We used a genetic screen in the developing Drosophila melanogaster eye to investigate the mechanisms that trigger quiescent cells to re-enter the cell cycle and proliferate in response to tissue damage. We discovered that Hippo signaling regulates compensatory proliferation after extensive cell death in the developing eye. Scalloped and Yorkie, transcriptional effectors of the Hippo pathway, drive Cyclin E expression to induce cell cycle re-entry in cells that normally remain quiescent in the absence of damage. Ajuba, an upstream regulator of Hippo signaling that functions as a sensor of epithelial integrity, is also required for cell cycle re-entry. Thus, in addition to its well-established role in modulating proliferation during periods of tissue growth, Hippo signaling maintains homeostasis by regulating quiescent cell populations affected by tissue damage.
authors.affiliation: Curriculum in Genetics & Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Joy H
authors.initials: JH
authors.lastname: Meserve
authors.affiliation: Curriculum in Genetics & Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC 27599, USA Departments of Biology and Genetics, University of North Carolina, Chapel Hill, NC 27599, USA Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA duronio@med.unc.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Duronio
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D019927:Cyclin E; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D005123:Eye / Q000196:embryology*; D005260:Female; D007091:Image Processing, Computer-Assisted; D017404:In Situ Hybridization, Fluorescence; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000091102:YAP-Signaling Proteins; D001616:beta-Galactosidase; D000099317:Hippo Kinases
chemical_list: D019927:Cyclin E; D029721:Drosophila Proteins; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; D001616:beta-Galactosidase; C503814:Yki protein, Drosophila; C087984:sd protein, Drosophila; C007293:DAPI; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
keywords: Apoptosis; Cell cycle; Compensatory proliferation; Drosophila; Hippo signaling; Quiescence; Regeneration