1. Developmental Biology
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Hox-dependent coordination of mouse cardiac progenitor cell patterning and differentiation

  1. Sonia Stefanovic
  2. Brigitte Laforest
  3. Jean-Pierre Desvignes
  4. Fabienne Lescroart
  5. Laurent Argiro
  6. Corinne Maurel-Zaffran
  7. David Salgado
  8. Elise Plaindoux
  9. Christopher De Bono
  10. Kristijan Pazur
  11. Magali Théveniau-Ruissy
  12. Christophe Béroud
  13. Michel Puceat
  14. Anthony Gavalas
  15. Robert G Kelly
  16. Stephane Zaffran  Is a corresponding author
  1. Aix Marseille University, France
  2. University of Chicago, United States
  3. Aix-Marseille Université, France
  4. CNRS-AMU, France
  5. Technische Universität Dresden, Germany
Research Article
  • Cited 10
  • Views 1,587
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Cite this article as: eLife 2020;9:e55124 doi: 10.7554/eLife.55124

Abstract

Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterior and posterior SHF sub-populations at genome-wide levels and demonstrate that Hoxb1 negatively regulates differentiation in the posterior SHF. Spatial mis-expression of Hoxb1 in the anterior SHF results in hypoplastic right ventricle. Activation of Hoxb1 in embryonic stem cells arrests cardiac differentiation, whereas Hoxb1-deficient mouse embryos display premature cardiac differentiation. Moreover, ectopic differentiation in the posterior SHF of embryos lacking both Hoxb1 and its paralog Hoxa1 results in atrioventricular septal defects. Our results show that Hoxb1 plays a key role in patterning cardiac progenitor cells that contribute to both cardiac poles and provide new insights into the pathogenesis of CHD.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2 and 3.

Article and author information

Author details

  1. Sonia Stefanovic

    INSERM, MMG, U1251, Aix Marseille University, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Brigitte Laforest

    Department of Pediatrics, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6919-8922
  3. Jean-Pierre Desvignes

    INSERM, MMG, U1251, Aix Marseille University, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Fabienne Lescroart

    INSERM, MMG, U1251, Aix-Marseille Université, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4942-7921
  5. Laurent Argiro

    INSERM, MMG, U1251, Aix Marseille University, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Corinne Maurel-Zaffran

    IBDM, CNRS-AMU, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  7. David Salgado

    INSERM, MMG, U1251, Aix Marseille University, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Elise Plaindoux

    INSERM, MMG, U1251, Aix Marseille University, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Christopher De Bono

    IBDM, CNRS UMR7288, Aix Marseille University, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Kristijan Pazur

    Paul Langerhans Institute Dresden of Helmholtz Centre Munich, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Magali Théveniau-Ruissy

    INSERM U1251 Marseille Medical Genetics, Aix Marseille University, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7346-7096
  12. Christophe Béroud

    INSERM, MMG, U1251, Aix Marseille University, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  13. Michel Puceat

    INSERM U1251 Marseille Medical Genetics, Aix Marseille University, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9055-7563
  14. Anthony Gavalas

    Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  15. Robert G Kelly

    CNRS UMR 7288, Aix-Marseille Université, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  16. Stephane Zaffran

    INSERM, MMG, U1251, Aix Marseille University, Marseille, France
    For correspondence
    stephane.zaffran@univ-amu.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0811-418X

Funding

Agence Nationale de la Recherche (ANR-13-BSV2-0003)

  • Michel Puceat
  • Robert G Kelly
  • Stephane Zaffran

Agence Nationale de la Recherche (ANR-18-CE13-0011)

  • Robert G Kelly
  • Stephane Zaffran

Fondation Lefoulon Delalande

  • Sonia Stefanovic
  • Fabienne Lescroart

Association Française contre les Myopathies (MNH-Decrypt)

  • Stephane Zaffran

Fondation pour la Recherche Médicale

  • Brigitte Laforest

Fondation pour la Recherche Médicale (DEQ20150331717)

  • Robert G Kelly

European Commission (H2020-MSCA-IF-2014)

  • Sonia Stefanovic

Fondation Leducq (Research Equipment and Technological Platform Awards)

  • Michel Puceat
  • Robert G Kelly
  • Stephane Zaffran

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal procedures were carried out under protocols approved by a national appointed ethical committee for animal experimentation (Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche; Authorization N{degree sign}32-08102012).

Reviewing Editor

  1. Richard P Harvey, Victor Chang Cardiac Research Institute, Australia

Publication history

  1. Received: January 13, 2020
  2. Accepted: August 16, 2020
  3. Accepted Manuscript published: August 17, 2020 (version 1)
  4. Version of Record published: September 1, 2020 (version 2)

Copyright

© 2020, Stefanovic 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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