1. Stem Cells and Regenerative Medicine
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Wilms Tumor 1b defines a wound-specific sheath cell subpopulation associated with notochord repair

  1. Juan Carlos Lopez-Baez
  2. Daniel J Simpson
  3. Laura LLeras Forero
  4. Zhiqiang Zeng
  5. Hannah Brunsdon
  6. Angela Salzano
  7. Alessandro Brombin
  8. Cameron Wyatt
  9. Witold Rybski
  10. Leonie F A Huitema
  11. Rodney M Dale
  12. Koichi Kawakami
  13. Christoph Englert
  14. Tamir Chandra
  15. Stefan Schulte-Merker
  16. Nicholas D Hastie  Is a corresponding author
  17. E Elizabeth Patton  Is a corresponding author
  1. University of Edinburgh, United Kingdom
  2. Hubrecht Institute, Netherlands
  3. Loyola University Chicago Quinlan, United States
  4. National Institute of Genetics, Japan
  5. Leibniz Institute for Age Research-Fritz Lipmann Institute, Germany
Research Article
  • Cited 9
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Cite this article as: eLife 2018;7:e30657 doi: 10.7554/eLife.30657

Abstract

Regenerative therapy for degenerative spine disorders requires the identification of cells that can slow down and possibly reverse degenerative processes. Here, we identify an unanticipated wound-specific notochord sheath cell subpopulation that expresses Wilms Tumor (WT) 1b following injury in zebrafish. We show that localized damage leads to Wt1b expression in sheath cells, and that wt1b+ cells migrate into the wound to form a stopper-like structure, likely to maintain structural integrity. Wt1b+ sheath cells are distinct in expressing cartilage and vacuolar genes, and in repressing a Wt1b-p53 transcriptional programme. At the wound, wt1b+ and entpd5+ cells constitute separate, tightly-associated subpopulations. Surprisingly, wt1b expression at the site of injury is maintained even into adult stages in developing vertebra, which forms in an untypical manner via a cartilage intermediate. Given that notochord cells are retained in adult intervertebral discs, the identification of novel subpopulations may have important implications for regenerative spine disorder treatments.

Article and author information

Author details

  1. Juan Carlos Lopez-Baez

    MRC Human Genetics Unit, MRC Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Daniel J Simpson

    MRC Human Genetics Unit, MRC Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Laura LLeras Forero

    KNAW and UMC Utrecht, Hubrecht Institute, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Zhiqiang Zeng

    MRC Human Genetics Unit, MRC Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Hannah Brunsdon

    MRC Human Genetics Unit, MRC Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Angela Salzano

    MRC Human Genetics Unit, MRC Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Alessandro Brombin

    MRC Human Genetics Unit, MRC Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Cameron Wyatt

    MRC Human Genetics Unit, MRC Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Witold Rybski

    MRC Human Genetics Unit, MRC Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6025-2918
  10. Leonie F A Huitema

    KNAW and UMC Utrecht, Hubrecht Institute, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  11. Rodney M Dale

    Department of Biology, Loyola University Chicago Quinlan, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4255-4741
  12. Koichi Kawakami

    Division of Molecular and Developmental Biology, National Institute of Genetics, Mishima, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9993-1435
  13. Christoph Englert

    Department of Molecular Genetics, Leibniz Institute for Age Research-Fritz Lipmann Institute, Jena, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5931-3189
  14. Tamir Chandra

    MRC Human Genetics Unit, MRC Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  15. Stefan Schulte-Merker

    KNAW and UMC Utrecht, Hubrecht Institute, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3617-8807
  16. Nicholas D Hastie

    MRC Human Genetics Unit, MRC Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    Nick.Hastie@igmm.ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  17. E Elizabeth Patton

    MRC Human Genetics Unit, MRC Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    e.patton@igmm.ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2570-0834

Funding

Medical Research Council University Unit Award to the University of Edinburgh for the MRC Human Genetics Unit (U127527202)

  • Juan Carlos Lopez-Baez
  • Zhiqiang Zeng
  • Alessandro Brombin
  • Witold Rybski
  • Nicholas D Hastie
  • E Elizabeth Patton

Japan Society for the Promotion of Science (15H02370)

  • Koichi Kawakami

Japan Agency for Medical Research and Development (National BioResource Project)

  • Koichi Kawakami

H2020 European Research Council (ZF-MEL-CHEMBIO - 648489)

  • Hannah Brunsdon
  • Alessandro Brombin
  • E Elizabeth Patton

Melanoma Research Alliance (401181)

  • Alessandro Brombin
  • E Elizabeth Patton

L'Oreal USA (401181)

  • Alessandro Brombin
  • E Elizabeth Patton

Cells in Motion - Cluster of Excellence

  • Stefan Schulte-Merker

Leibniz-Gemeinschaft

  • Christoph Englert

Medical Research Council (Discovery Award MC_PC_15075)

  • Angela Salzano

University Of Edinburgh (Chancellor's Fellowship)

  • Tamir Chandra

Medical Research Council (Doctoral Training Programme in Percision Medicine)

  • Daniel J Simpson

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

Ethics

Animal experimentation: All work presented in this study has been performed in accordance with the UK legal requirements for the protection of animals used for experimental or other scientific research under the Animal (Scientific Procedures) Act 1986. All experiments were approved by the University of Edinburgh Ethics Committee, and performed under the Home Office Project License 70/800 to EEP. Zebrafish welfare and husbandry were closely monitored by the MRC Human Genetics Unit Zebrafish Facility staff.

Reviewing Editor

  1. Michel Bagnat, Duke University, United States

Publication history

  1. Received: July 27, 2017
  2. Accepted: February 2, 2018
  3. Accepted Manuscript published: February 6, 2018 (version 1)
  4. Version of Record published: February 13, 2018 (version 2)

Copyright

© 2018, Lopez-Baez 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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