1. Developmental Biology
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BMP and FGF signaling interact to pattern mesoderm by controlling basic helix-loop-helix transcription factor activity

  1. Richard H Row
  2. Amy Pegg
  3. Brian Kinney
  4. Gist H Farr
  5. Lisa Maves
  6. Sally Lowell  Is a corresponding author
  7. Valerie Wilson  Is a corresponding author
  8. Benjamin Louis Martin  Is a corresponding author
  1. Stony Brook University, United States
  2. University of Edinburgh, United Kingdom
  3. Seattle Children's Research Institute, United States
Research Article
  • Cited 6
  • Views 2,807
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Cite this article as: eLife 2018;7:e31018 doi: 10.7554/eLife.31018

Abstract

The mesodermal germ layer is patterned into mediolateral subtypes by signaling factors including BMP and FGF. How these pathways are integrated to induce specific mediolateral cell fates is not well understood. We used mesoderm derived from post-gastrulation neuromesodermal progenitors (NMPs), which undergo a binary mediolateral patterning decision, as a simplified model to understand how FGF acts together with BMP to impart mediolateral fate. Using zebrafish and mouse NMPs, we identify an evolutionarily conserved mechanism of BMP and FGF mediated mediolateral mesodermal patterning that occurs through modulation of basic helix-loop-helix (bHLH) transcription factor activity. BMP imparts lateral fate through induction of Id helix loop helix (HLH) proteins, which antagonize bHLH transcription factors, induced by FGF signaling, that specify medial fate. We extend our analysis of zebrafish development to show that bHLH activity is responsible for the mediolateral patterning of the entire mesodermal germ layer.

Article and author information

Author details

  1. Richard H Row

    Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Amy Pegg

    MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Brian Kinney

    Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Gist H Farr

    Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Lisa Maves

    Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Sally Lowell

    MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    sally.lowell@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4018-9480
  7. Valerie Wilson

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    v.wilson@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4182-5159
  8. Benjamin Louis Martin

    Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    For correspondence
    benjamin.martin@stonybrook.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5474-4492

Funding

National Science Foundation (CAREER Award IOS1452928)

  • Benjamin Louis Martin

American Heart Association (National Scientist Development Grant 13SDG14360032)

  • Benjamin Louis Martin

National Institute of Arthritis and Musculoskeletal and Skin Diseases (R03 AR065760)

  • Lisa Maves

Medical Research Council (Mr/K011200/1)

  • Valerie Wilson

Wellcome (Senior Fellowship in Basic Biomedical Science 103789/Z/14/Z)

  • Sally Lowell

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 accordance with and approval from the Stony Brook University Institutional Animal Use and Care Committee (IACUC) (protocol # 301537), Seattle Children's Research Institute IACUC (protocol # 14109), and the Animal Welfare and Ethical Review Panel of the MRC Centre for Regenerative Medicine and within the conditions of the Animals (Scientific Procedures) Act of 1986 (UK Home Office project license PPL60/4435).

Reviewing Editor

  1. Deborah Yelon, University of California, San Diego, United States

Publication history

  1. Received: August 3, 2017
  2. Accepted: May 26, 2018
  3. Accepted Manuscript published: June 7, 2018 (version 1)
  4. Version of Record published: June 21, 2018 (version 2)

Copyright

© 2018, Row 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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