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Chamber identity programs drive early functional partitioning of the heart

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  • Christian Mosimann

    (Howard Hughes Medical Institute
    Stem Cell Program, Boston Children’s Hospital
    Boston Children’s Hospital, Harvard Stem Cell Institute, Harvard Medical School
    Institute of Molecular Life Sciences (IMLS), University of Zürich)

  • Daniela Panáková

    (Brigham and Women's Hospital, Harvard Medical School
    Present addresses: Max-Delbrück Center for Molecular Medicine (MDC), 13125 Berlin-Buch, Germany)

  • Andreas A. Werdich

    (Brigham and Women's Hospital, Harvard Medical School)

  • Gabriel Musso

    (Brigham and Women's Hospital, Harvard Medical School)

  • Alexa Burger

    (Institute of Molecular Life Sciences (IMLS), University of Zürich)

  • Katy L. Lawson

    (Howard Hughes Medical Institute
    Stem Cell Program, Boston Children’s Hospital
    Boston Children’s Hospital, Harvard Stem Cell Institute, Harvard Medical School)

  • Logan A. Carr

    (Howard Hughes Medical Institute
    Stem Cell Program, Boston Children’s Hospital
    Boston Children’s Hospital, Harvard Stem Cell Institute, Harvard Medical School)

  • Kathleen R. Nevis

    (Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School)

  • M. Khaled Sabeh

    (Brigham and Women's Hospital, Harvard Medical School)

  • Yi Zhou

    (Howard Hughes Medical Institute
    Stem Cell Program, Boston Children’s Hospital
    Boston Children’s Hospital, Harvard Stem Cell Institute, Harvard Medical School)

  • Alan J. Davidson

    (Howard Hughes Medical Institute
    Stem Cell Program, Boston Children’s Hospital
    Boston Children’s Hospital, Harvard Stem Cell Institute, Harvard Medical School)

  • Anthony DiBiase

    (Howard Hughes Medical Institute
    Stem Cell Program, Boston Children’s Hospital
    Boston Children’s Hospital, Harvard Stem Cell Institute, Harvard Medical School)

  • Caroline E. Burns

    (Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School)

  • C. Geoffrey Burns

    (Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School)

  • Calum A. MacRae

    (Brigham and Women's Hospital, Harvard Medical School)

  • Leonard I. Zon

    (Howard Hughes Medical Institute
    Stem Cell Program, Boston Children’s Hospital
    Boston Children’s Hospital, Harvard Stem Cell Institute, Harvard Medical School)

Abstract

The vertebrate heart muscle (myocardium) develops from the first heart field (FHF) and expands by adding second heart field (SHF) cells. While both lineages exist already in teleosts, the primordial contributions of FHF and SHF to heart structure and function remain incompletely understood. Here we delineate the functional contribution of the FHF and SHF to the zebrafish heart using the cis-regulatory elements of the draculin (drl) gene. The drl reporters initially delineate the lateral plate mesoderm, including heart progenitors. Subsequent myocardial drl reporter expression restricts to FHF descendants. We harnessed this unique feature to uncover that loss of tbx5a and pitx2 affect relative FHF versus SHF contributions to the heart. High-resolution physiology reveals distinctive electrical properties of each heart field territory that define a functional boundary within the single zebrafish ventricle. Our data establish that the transcriptional program driving cardiac septation regulates physiologic ventricle partitioning, which successively provides mechanical advantages of sequential contraction.

Suggested Citation

  • Christian Mosimann & Daniela Panáková & Andreas A. Werdich & Gabriel Musso & Alexa Burger & Katy L. Lawson & Logan A. Carr & Kathleen R. Nevis & M. Khaled Sabeh & Yi Zhou & Alan J. Davidson & Anthony , 2015. "Chamber identity programs drive early functional partitioning of the heart," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9146
    DOI: 10.1038/ncomms9146
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    Cited by:

    1. Karin D. Prummel & Helena L. Crowell & Susan Nieuwenhuize & Eline C. Brombacher & Stephan Daetwyler & Charlotte Soneson & Jelena Kresoja-Rakic & Agnese Kocere & Manuel Ronner & Alexander Ernst & Zahra, 2022. "Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    2. Andrew P Holmes & Ting Y Yu & Samantha Tull & Fahima Syeda & Stefan M Kuhlmann & Sian-Marie O’Brien & Pushpa Patel & Keith L Brain & Davor Pavlovic & Nigel A Brown & Larissa Fabritz & Paulus Kirchhof, 2016. "A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity," PLOS ONE, Public Library of Science, vol. 11(5), pages 1-17, May.

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