Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly

  1. Joshua Bloomekatz
  2. Reena Singh
  3. Owen WJ Prall
  4. Ariel C Dunn
  5. Megan Vaughan
  6. Chin-San Loo
  7. Richard P Harvey  Is a corresponding author
  8. Deborah Yelon  Is a corresponding author
  1. University of California, San Diego, United States
  2. Victor Chang Cardiac Research Institute, Australia

Abstract

Communication between neighboring tissues plays a central role in guiding organ morphogenesis. During heart tube assembly, interactions with the adjacent endoderm control the medial movement of cardiomyocytes, a process referred to as cardiac fusion. However, the molecular underpinnings of this endodermal-myocardial relationship remain unclear. Here, we show an essential role for platelet-derived growth factor receptor alpha (Pdgfra) in directing cardiac fusion. Mutation of pdgfra disrupts heart tube assembly in both zebrafish and mouse. Timelapse analysis of individual cardiomyocyte trajectories reveals misdirected cells in zebrafish pdgfra mutants, suggesting that PDGF signaling steers cardiomyocytes toward the midline during cardiac fusion. Intriguingly, the ligand pdgfaa is expressed in the endoderm medial to the pdgfra-expressing myocardial precursors. Ectopic expression of pdgfaa interferes with cardiac fusion, consistent with an instructive role for PDGF signaling. Together, these data uncover a novel mechanism through which endodermal-myocardial communication can guide the cell movements that initiate cardiac morphogenesis.

Article and author information

Author details

  1. Joshua Bloomekatz

    Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  2. Reena Singh

    Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Competing interests
    No competing interests declared.
  3. Owen WJ Prall

    Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Competing interests
    No competing interests declared.
  4. Ariel C Dunn

    Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  5. Megan Vaughan

    Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  6. Chin-San Loo

    Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  7. Richard P Harvey

    Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    For correspondence
    r.harvey@victorchang.edu.au
    Competing interests
    Richard P Harvey, Reviewing editor, eLife.
  8. Deborah Yelon

    Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    For correspondence
    dyelon@ucsd.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3523-4053

Funding

National Heart, Lung, and Blood Institute (R01HL081911 and R01HL133166)

  • Deborah Yelon

March of Dimes Foundation (1-FY11-493)

  • Deborah Yelon

National Health and Medical Research Council (NHMRC 1074386; 573732; 5737707; 573705)

  • Owen WJ Prall
  • Richard P Harvey

Australian Research Council (Stem Cells Australia SR110001002)

  • Richard P Harvey

American Heart Association (12POST11660038)

  • Joshua Bloomekatz

Australian Heart Foundation (CR 08S 3958)

  • Owen WJ Prall

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 zebrafish work followed protocols approved by the UCSD IACUC (protocol S09125). All mouse experiments were overseen by the Garvan Institute of Medical Research/St. Vincent's Hospital Animal Ethics Committee (projects AEC13/01 and AEC13/02).

Reviewing Editor

  1. Didier YR Stainier, Max Planck Institute for Heart and Lung Research, Germany

Publication history

  1. Received: September 1, 2016
  2. Accepted: January 17, 2017
  3. Accepted Manuscript published: January 18, 2017 (version 1)
  4. Version of Record published: February 8, 2017 (version 2)

Copyright

© 2017, Bloomekatz 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. Joshua Bloomekatz
  2. Reena Singh
  3. Owen WJ Prall
  4. Ariel C Dunn
  5. Megan Vaughan
  6. Chin-San Loo
  7. Richard P Harvey
  8. Deborah Yelon
(2017)
Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly
eLife 6:e21172.
https://doi.org/10.7554/eLife.21172

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