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Elife. 2018 Jun 7;7. pii: e31018. doi: 10.7554/eLife.31018.

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

Author information

1
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States.
2
MRC Center for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
3
Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, United States.
4
Division of Cardiology, Department of Pediatrics, University of Washington, Seattle, United States.
#
Contributed equally

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.

KEYWORDS:

BMP; FGF; bHLH; developmental biology; mesoderm; morphogen; mouse; neuromesodermal progenitor; regenerative medicine; stem cells; zebrafish

PMID:
29877796
PMCID:
PMC6013256
DOI:
10.7554/eLife.31018
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

RR, AP, BK, GF, LM, SL, VW, BM No competing interests declared

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