1. Stem Cells and Regenerative Medicine
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CtBP impedes JNK- and Upd/STAT-driven cell fate misspecifications in regenerating Drosophila imaginal discs

  1. Melanie I Worley
  2. Larissa A Alexander
  3. Iswar K Hariharan  Is a corresponding author
  1. University of California, Berkeley, United States
Research Article
  • Cited 11
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Cite this article as: eLife 2018;7:e30391 doi: 10.7554/eLife.30391

Abstract

Regeneration following tissue damage often necessitates a mechanism for cellular re-programming, so that surviving cells can give rise to all cell types originally found in the damaged tissue. This process, if unchecked, can also generate cell types that are inappropriate for a given location. We conducted a screen for genes that negatively regulate the frequency of notum-to-wing transformations following genetic ablation and regeneration of the wing pouch, from which we identified mutations in the transcriptional co-repressor C-terminal Binding Protein (CtBP). When CtBP function is reduced, ablation of the pouch can activate the JNK/AP-1 and JAK/STAT pathways in the notum to destabilize cell fates. Ectopic expression of Wingless and Dilp8 precede the formation of the ectopic pouch, which is subsequently generated by recruitment of both anterior and posterior cells near the compartment boundary. Thus, CtBP stabilizes cell fates following damage by opposing the destabilizing effects of the JNK/AP-1 and JAK/STAT pathways.

Article and author information

Author details

  1. Melanie I Worley

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Larissa A Alexander

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Iswar K Hariharan

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    ikh@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6505-0744

Funding

National Institute of General Medical Sciences (GM061672)

  • Iswar K Hariharan

American Cancer Society (RP-16-238-06-COUN)

  • Iswar K Hariharan

National Institute of General Medical Sciences (GM085576)

  • Iswar K Hariharan

National Institute of General Medical Sciences (GM122490)

  • Iswar K Hariharan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Bruce Edgar, University of Utah, United States

Publication history

  1. Received: July 13, 2017
  2. Accepted: January 19, 2018
  3. Accepted Manuscript published: January 26, 2018 (version 1)
  4. Version of Record published: February 22, 2018 (version 2)

Copyright

© 2018, Worley et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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