Journal
ELIFE
Volume 7, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.31018
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Funding
- National Science Foundation CAREER Award [IOS1452928]
- American Heart Association [13SDG14360032]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [R03 AR065760]
- Medical Research Council [Mr/K011200/1]
- Wellcome Senior Fellowship in Basic Biomedical Science [103789/Z/14/Z]
- MRC [MR/K011200/1, MR/K017047/1] Funding Source: UKRI
- Wellcome Trust [103789/Z/14/Z] Funding Source: Wellcome Trust
- Medical Research Council [MR/K011200/1] Funding Source: researchfish
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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 helixloop-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.
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