Unique morphogenetic signatures define mammalian neck muscles and associated connective tissues

  1. Eglantine Heude
  2. Marketa Tesarova
  3. Elizabeth M Sefton
  4. Estelle Jullian
  5. Noritaka Adachi
  6. Alexandre Grimaldi
  7. Tomas Zikmund
  8. Jozef Kaiser
  9. Gabrielle Kardon
  10. Robert G Kelly
  11. Shahragim Tajbakhsh  Is a corresponding author
  1. Institut Pasteur, France
  2. Brno University of Technology, Czech Republic
  3. University of Utah, United States
  4. Aix-Marseille Université, France

Abstract

In vertebrates, head and trunk muscles develop from different mesodermal populations and are regulated by distinct genetic networks. Neck muscles at the head-trunk interface remain poorly defined due to their complex morphogenesis and dual mesodermal origins. Here, we use genetically modified mice to establish a 3D model that integrates regulatory genes, cell populations and morphogenetic events that define this transition zone. We show that the evolutionary conserved cucullaris-derived muscles originate from posterior cardiopharyngeal mesoderm, not lateral plate mesoderm, and we define new boundaries for neural crest and mesodermal contributions to neck connective tissue. Furthermore, lineage studies and functional analysis of Tbx1- and Pax3-null mice reveal a unique developmental program for somitic neck muscles that is distinct from that of somitic trunk muscles. Our findings unveil the embryological and developmental requirements underlying tetrapod neck myogenesis and provide a blueprint to investigate how muscle subsets are selectively affected in some human myopathies.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Eglantine Heude

    Department of Developmental and Stem Cell Biology, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Marketa Tesarova

    Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  3. Elizabeth M Sefton

    Department of Human Genetics, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6481-612X
  4. Estelle Jullian

    CNRS UMR 7288, Aix-Marseille Université, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Noritaka Adachi

    CNRS UMR 7288, 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:" 0000-0002-9482-8436
  6. Alexandre Grimaldi

    Department of Developmental and Stem Cell Biology, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Tomas Zikmund

    Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  8. Jozef Kaiser

    Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  9. Gabrielle Kardon

    Department of Human Genetics, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Robert G Kelly

    CNRS UMR 7288, Aix-Marseille Université, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Shahragim Tajbakhsh

    Department of Developmental & Stem Cell Biology, Institut Pasteur, Paris, France
    For correspondence
    shahragim.tajbakhsh@pasteur.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1809-7202

Funding

Institut Pasteur

  • Eglantine Heude
  • Alexandre Grimaldi
  • Shahragim Tajbakhsh

National Institutes of Health

  • Elizabeth M Sefton
  • Gabrielle Kardon

Agence Nationale de la Recherche

  • Eglantine Heude
  • Alexandre Grimaldi
  • Shahragim Tajbakhsh

Centre National de la Recherche Scientifique

  • Eglantine Heude
  • Estelle Jullian
  • Noritaka Adachi
  • Alexandre Grimaldi
  • Robert G Kelly
  • Shahragim Tajbakhsh

Association Française contre les Myopathies

  • Eglantine Heude
  • Alexandre Grimaldi
  • Shahragim Tajbakhsh

Central European Institute of Technology

  • Marketa Tesarova
  • Tomas Zikmund
  • Jozef Kaiser

March of Dimes Foundation

  • Elizabeth M Sefton
  • Gabrielle Kardon

Fondation pour la Recherche Médicale

  • Estelle Jullian
  • Noritaka Adachi
  • Robert G Kelly

Fondation Leducq

  • Estelle Jullian
  • Noritaka Adachi
  • Robert G Kelly

Yamada Science Foundation

  • Noritaka Adachi
  • Robert G Kelly

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

Reviewing Editor

  1. Clare Blackburn, MRC Centre for Regenerative Medicine, University of Edinburgh, United Kingdom

Ethics

Animal experimentation: Animals were handled as per European Community guidelines and the ethics committee of the Institut Pasteur (CTEA) approved protocols. (APAFIS#6354-20160809l2028839)

Version history

  1. Received: July 17, 2018
  2. Accepted: November 17, 2018
  3. Accepted Manuscript published: November 19, 2018 (version 1)
  4. Version of Record published: December 28, 2018 (version 2)

Copyright

© 2018, Heude 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

  • 3,240
    views
  • 598
    downloads
  • 50
    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. Eglantine Heude
  2. Marketa Tesarova
  3. Elizabeth M Sefton
  4. Estelle Jullian
  5. Noritaka Adachi
  6. Alexandre Grimaldi
  7. Tomas Zikmund
  8. Jozef Kaiser
  9. Gabrielle Kardon
  10. Robert G Kelly
  11. Shahragim Tajbakhsh
(2018)
Unique morphogenetic signatures define mammalian neck muscles and associated connective tissues
eLife 7:e40179.
https://doi.org/10.7554/eLife.40179

Share this article

https://doi.org/10.7554/eLife.40179

Further reading

    1. Developmental Biology
    2. Neuroscience
    Melody C Iacino, Taylor A Stowe ... Mark J Ferris
    Research Article

    Adolescence is characterized by changes in reward-related behaviors, social behaviors, and decision making. These behavioral changes are necessary for the transition into adulthood, but they also increase vulnerability to the development of a range of psychiatric disorders. Major reorganization of the dopamine system during adolescence is thought to underlie, in part, the associated behavioral changes and increased vulnerability. Here, we utilized fast scan cyclic voltammetry and microdialysis to examine differences in dopamine release as well as mechanisms that underlie differential dopamine signaling in the nucleus accumbens (NAc) core of adolescent (P28-35) and adult (P70-90) male rats. We show baseline differences between adult and adolescent stimulated dopamine release in male rats, as well as opposite effects of the a6 nicotinic acetylcholine receptor (nAChR) on modulating dopamine release. The a6-selective blocker, a-conotoxin, increased dopamine release in early adolescent rats, but decreased dopamine release in rats beginning in middle adolescence and extending through adulthood. Strikingly, blockade of GABAA and GABAB receptors revealed that this a6-mediated increase in adolescent dopamine release requires NAc GABA signaling to occur. We confirm the role of a6 nAChR and GABA in mediating this effect in vivo using microdialysis. Results herein suggest a multisynaptic mechanism potentially unique to the period of development that includes early adolescence, involving acetylcholine acting at a6-containing nAChRs to drive inhibitory GABA tone on dopamine release.

    1. Developmental Biology
    Yongfeng Luo, Ke Cao ... Wei Shi
    Research Article

    Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study using genetic mouse models, we dissected the roles of bone morphogenetic protein (BMP) receptor 1a (Bmpr1a)-mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.