title: Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity.
abstract: BACKGROUND
  The p53 transcription factor directs a transcriptional program that determines whether a cell lives or dies after DNA damage. Animal survival after extensive cellular damage often requires that lost tissue be replaced through compensatory growth or regeneration. In Drosophila, damaged imaginal disc cells can induce the proliferation of neighboring viable cells, but how this is controlled is not clear. Here we provide evidence that Drosophila p53 (dp53) has a previously unidentified role in coordinating the compensatory growth response to tissue damage.
  
  
  RESULTS
  We find that dp53, the sole p53 ortholog in Drosophila, is required for each component of the response to cellular damage, including two separate cell-cycle arrests, changes in patterning gene expression, cell proliferation, and growth. We demonstrate that these processes are regulated by dp53 in a manner that is independent of DNA-damage sensing but that requires the initiator caspase Dronc. Our results indicate that once induced, dp53 amplifies and sustains the response through a positive feedback loop with Dronc and the apoptosis-inducing factors Hid and Reaper.
  
  
  CONCLUSIONS
  How cell death and cell proliferation are coordinated during development and after stress is a fundamental question that is critical for an understanding of growth regulation. Our data suggest that dp53 may carry out an ancestral function that promotes animal survival through the coordination of responses leading to compensatory growth after tissue damage.
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Brent S
authors.initials: BS
authors.lastname: Wells
authors.forename: Eri
authors.initials: E
authors.lastname: Yoshida
authors.forename: Laura A
authors.initials: LA
authors.lastname: Johnston
mesh_terms: D000818:Animals; D020169:Caspases / Q000378:metabolism* / Q000502:physiology; D049109:Cell Proliferation; D004330:Drosophila / Q000254:growth & development*; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology; D005121:Extremities / Q000502:physiology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007814:Larva / Q000254:growth & development / Q000502:physiology; D009024:Morphogenesis / Q000502:physiology; D012038:Regeneration / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism* / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D016159:Tumor Suppressor Protein p53; C474203:p53 protein, Drosophila; D020169:Caspases; C118731:dronc protein, Drosophila