BMP and FGF signaling interact to pattern mesoderm by controlling basic helix-loop-helix transcription factor activity
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.
Transgenic fish lines generated for this study will be made available through the Zebrafish International Resource Center. The raw data for the qPCR experiments is available as Figure 2-source data 1, Figure 5-source data 1 and Figure 6-source data 1.
Article and author information
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.
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).
- Deborah Yelon, University of California, San Diego, United States
- Received: August 3, 2017
- Accepted: May 26, 2018
- Accepted Manuscript published: June 7, 2018 (version 1)
- Version of Record published: June 21, 2018 (version 2)
© 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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