Reciprocal analyses in zebrafish and medaka reveal that harnessing the immune response promotes cardiac regeneration

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.

Data availability

The following data sets were generated

Article and author information

Author details

  1. Shih-Lei Lai

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

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

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  4. 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.
  5. 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.
  6. Ayele Taddese Tsedeke

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  7. 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.
  8. 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.
  9. 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

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).

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.

Metrics

  • 10,242
    views
  • 1,423
    downloads
  • 209
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Shih-Lei Lai
  2. Rubén Marín-Juez
  3. Pedro Luís Moura
  4. Carsten Kuenne
  5. Jason Kuan Han Lai
  6. Ayele Taddese Tsedeke
  7. Stefan Guenther
  8. Mario Looso
  9. Didier YR Stainier
(2017)
Reciprocal analyses in zebrafish and medaka reveal that harnessing the immune response promotes cardiac regeneration
eLife 6:e25605.
https://doi.org/10.7554/eLife.25605

Share this article

https://doi.org/10.7554/eLife.25605

Further reading

    1. Developmental Biology
    Ming-Ming Chen, Yue Zhao ... Zheng-Xing Lian
    Research Article

    Mutations in the well-known Myostatin (MSTN) produce a ‘double-muscle’ phenotype, which makes it commercially invaluable for improving livestock meat production and providing high-quality protein for humans. However, mutations at different loci of the MSTN often produce a variety of different phenotypes. In the current study, we increased the delivery ratio of Cas9 mRNA to sgRNA from the traditional 1:2 to 1:10, which improves the efficiency of the homozygous mutation of biallelic gene. Here, a MSTNDel73C mutation with FGF5 knockout sheep, in which the MSTN and FGF5 dual-gene biallelic homozygous mutations were produced via the deletion of 3-base pairs of AGC in the third exon of MSTN, resulting in cysteine-depleted at amino acid position 73, and the FGF5 double allele mutation led to inactivation of FGF5 gene. The MSTNDel73C mutation with FGF5 knockout sheep highlights a dominant ‘double-muscle’ phenotype, which can be stably inherited. Both F0 and F1 generation mutants highlight the excellent trait of high-yield meat with a smaller cross-sectional area and higher number of muscle fibers per unit area. Mechanistically, the MSTNDel73C mutation with FGF5 knockout mediated the activation of FOSL1 via the MEK-ERK-FOSL1 axis. The activated FOSL1 promotes skeletal muscle satellite cell proliferation and inhibits myogenic differentiation by inhibiting the expression of MyoD1, and resulting in smaller myotubes. In addition, activated ERK1/2 may inhibit the secondary fusion of myotubes by Ca2+-dependent CaMKII activation pathway, leading to myoblasts fusion to form smaller myotubes.

    1. Developmental Biology
    Wenyue Guan, Ziyan Nie ... Jonathan Enriquez
    Research Article

    Neuronal stem cells generate a limited and consistent number of neuronal progenies, each possessing distinct morphologies and functions, which are crucial for optimal brain function. Our study focused on a neuroblast (NB) lineage in Drosophila known as Lin A/15, which generates motoneurons (MNs) and glia. Intriguingly, Lin A/15 NB dedicates 40% of its time to producing immature MNs (iMNs) that are subsequently eliminated through apoptosis. Two RNA-binding proteins, Imp and Syp, play crucial roles in this process. Imp+ MNs survive, while Imp−, Syp+ MNs undergo apoptosis. Genetic experiments show that Imp promotes survival, whereas Syp promotes cell death in iMNs. Late-born MNs, which fail to express a functional code of transcription factors (mTFs) that control their morphological fate, are subject to elimination. Manipulating the expression of Imp and Syp in Lin A/15 NB and progeny leads to a shift of TF code in late-born MNs toward that of early-born MNs, and their survival. Additionally, introducing the TF code of early-born MNs into late-born MNs also promoted their survival. These findings demonstrate that the differential expression of Imp and Syp in iMNs links precise neuronal generation and distinct identities through the regulation of mTFs. Both Imp and Syp are conserved in vertebrates, suggesting that they play a fundamental role in precise neurogenesis across species.