Apelin signaling dependent endocardial protrusions promote cardiac trabeculation in zebrafish

  1. Jialing Qi
  2. Annegret Rittershaus
  3. Rashmi Priya
  4. Shivani Mansingh
  5. Didier YR Stainier  Is a corresponding author
  6. Christian SM Helker  Is a corresponding author
  1. Max Planck Institute for Heart and Lung Research, Germany
  2. Philipps-University Marburg, Germany

Abstract

During cardiac development, endocardial cells (EdCs) produce growth factors to promote myocardial morphogenesis and growth. In particular, EdCs produce Neuregulin which is required for ventricular cardiomyocytes (CMs) to seed the multicellular ridges known as trabeculae. Defects in Neuregulin signaling, or in endocardial sprouting towards CMs, cause hypotrabeculation. However, the mechanisms underlying endocardial sprouting remain largely unknown. Here, we first show by live imaging in zebrafish embryos that EdCs interact with CMs via dynamic membrane protrusions. After touching CMs, these protrusions remain in close contact with their target despite the vigorous cardiac contractions. Loss of the CM-derived peptide Apelin, or of the Apelin receptor, which is expressed in EdCs, leads to reduced endocardial sprouting and hypotrabeculation. Mechanistically, Neuregulin signaling requires endocardial protrusions to induce extracellular signal-regulated kinase (Erk) activity in CMs and trigger their delamination. Altogether, these data show that Apelin signaling dependent endocardial protrusions modulate CM behavior during trabeculation.

Data availability

Figure 2 - Source Data 1, Figure 4 - Source Data 1, Figure 5 - Source Data 1, Figure 6 - Source Data 1, and Supplementary File 1 contain the numerical data used to generate the figures.

Article and author information

Author details

  1. Jialing Qi

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  2. Annegret Rittershaus

    Philipps-University Marburg, Marburg, Germany
    Competing interests
    No competing interests declared.
  3. Rashmi Priya

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0510-7515
  4. Shivani Mansingh

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  5. 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
  6. Christian SM Helker

    Philipps-University Marburg, Marburg, Germany
    For correspondence
    christian.helker@biologie.uni-marburg.de
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0427-5338

Funding

Max-Planck-Gesellschaft

  • Didier YR Stainier

Deutsche Forschungsgemeinschaft (SFB834)

  • Didier YR Stainier
  • Christian SM Helker

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

Reviewing Editor

  1. Victoria L Bautch, University of North Carolina, Chapel Hill, United States

Ethics

Animal experimentation: All zebrafish husbandry was performed under standard conditions in accordance with institutional (MPG) and national (German) ethical and animal welfare regulations. All experiments conducted on animals conform to the guidelines from Directive 2010/63/EU of the European Parliament on the protection of animals used for scientific purposes and were approved by the Animal Protection Committee (Tierschutzkommission) of the Regierungspräsidium Darmstadt (Proposal numbers: B2/1017, B2/1041, B2/1138, B2/1218).

Version history

  1. Received: August 20, 2021
  2. Preprint posted: August 31, 2021 (view preprint)
  3. Accepted: February 25, 2022
  4. Accepted Manuscript published: February 28, 2022 (version 1)
  5. Version of Record published: March 11, 2022 (version 2)

Copyright

© 2022, Qi 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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  1. Jialing Qi
  2. Annegret Rittershaus
  3. Rashmi Priya
  4. Shivani Mansingh
  5. Didier YR Stainier
  6. Christian SM Helker
(2022)
Apelin signaling dependent endocardial protrusions promote cardiac trabeculation in zebrafish
eLife 11:e73231.
https://doi.org/10.7554/eLife.73231

Share this article

https://doi.org/10.7554/eLife.73231

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