1. Developmental Biology
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Reciprocal analyses in zebrafish and medaka reveal that harnessing the immune response promotes cardiac regeneration

  1. Didier YR Stainier  Is a corresponding author
  2. Shih-Lei Ben Lai  Is a corresponding author
  3. Rubén Marín-Juez
  4. Pedro Luís Moura
  5. Carsten Kuenne
  6. Jason Kuan Han Lai
  7. Ayele Taddese Tsedeke
  8. Stefan Guenther
  9. Mario Looso
  1. Max Planck Institute for Heart and Lung Research, Germany
  2. University of Bristol, United Kingdom
Research Article
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Cite this article as: eLife 2017;6:e25605 doi: 10.7554/eLife.25605

Abstract

Zebrafish display a distinct ability to regenerate their heart following injury. However, this ability is not shared by another teleost, the medaka. In order to identify cellular and molecular bases for this difference, we performed comparative transcriptomic analyses following cardiac cryoinjury. This comparison points to major differences in immune cell dynamics between these models. Upon closer examination, we observed delayed and reduced macrophage recruitment in medaka, along with delayed neutrophil clearance. To investigate the role of immune responses in cardiac regeneration, we delayed macrophage recruitment in zebrafish and observed compromised neovascularization, neutrophil clearance, cardiomyocyte proliferation and scar resolution. In contrast, stimulating Toll-like receptor signaling in medaka enhanced immune cell dynamics and promoted neovascularization, neutrophil clearance, cardiomyocyte proliferation and scar resolution. Altogether, these data provide further insight into the complex role of the immune response during regeneration, and serve as a platform to identify and test additional regulators of cardiac repair.

Article and author information

Author details

  1. Didier YR Stainier

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    For correspondence
    Didier.Stainier@mpi-bn.mpg.de
    Competing interests
    Didier YR Stainier, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0382-0026
  2. Shih-Lei Ben Lai

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    For correspondence
    ben.lai@mpi-bn.mpg.de
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1409-4701
  3. Rubén Marín-Juez

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  4. Pedro Luís Moura

    School of Biochemistry, University of Bristol, Bristol, United Kingdom
    Competing interests
    No competing interests declared.
  5. Carsten Kuenne

    ECCPS Bioinformatics and deep sequencing platform, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  6. Jason Kuan Han Lai

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  7. Ayele Taddese Tsedeke

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  8. Stefan Guenther

    ECCPS Bioinformatics and deep sequencing platform, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  9. Mario Looso

    ECCPS Bioinformatics and deep sequencing platform, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.

Funding

Max-Planck-Gesellschaft (Open-access funding)

  • Didier YR Stainier

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

Ethics

Animal experimentation: All zebrafish and medaka husbandry was performed under standard conditions, and all animal experiments were done in accordance with institutional (MPG) and national ethical and animal welfare guidelines approved by the ethics committee for animal experiments at the Regierungspräsidium Darmstadt, Germany (permit numbers B2-1023 and B2-1111).

Reviewing Editor

  1. Marianne Bronner, California Institute of Technology, United States

Publication history

  1. Received: January 30, 2017
  2. Accepted: June 15, 2017
  3. Accepted Manuscript published: June 20, 2017 (version 1)
  4. Accepted Manuscript updated: June 22, 2017 (version 2)
  5. Version of Record published: July 5, 2017 (version 3)

Copyright

© 2017, Stainier 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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