BMP and FGF signaling interact to pattern mesoderm by controlling basic helix-loop-helix transcription factor activity
- Stony Brook University, United States
- University of Edinburgh, United Kingdom
- Seattle Children's Research Institute, United States
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.
Data availability
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
Author details
Benjamin Louis Martin
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).
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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BMP and FGF signaling interact to pattern mesoderm by controlling basic helix-loop-helix transcription factor activity
eLife 7:e31018.
https://doi.org/10.7554/eLife.31018
Further reading
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The first cell-fate decision is the process by which cells of an embryo take on distinct lineage identities for the first time, thus representing the beginning of developmental patterning. Here, we demonstrate that the molecular chaperone heat shock protein A2 (HSPA2), a member of the 70 kDa heat shock protein (HSP70) family, is asymmetrically expressed in the late 2-cell stage of mouse embryos. The knockdown of Hspa2 in one of the 2-cell blastomeres prevented its progeny predominantly towards the inner cell mass (ICM) fate. In contrast, the overexpression of Hspa2 in one of the 2-cell blastomeres did not induce the blastomere to differentiate towards the ICM fate. Furthermore, we demonstrated that HSPA2 interacted with CARM1 and its levels correlated with ICM-associated genes. Collectively, our results identify HSPA2 as a critical early regulator of the first cell-fate decision in mammalian 2-cell embryos.
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