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PMID: 20702561 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Arterial pole progenitors interpret opposing FGF/BMP signals to proliferate or differentiate.

Development (Cambridge, England) ·Vol. 137 ·No. 18 ·2010-09-00 ·Pages 3001-11

Hutson MR, Zeng XL, Kim AJ, Antoon E, Harward S, Kirby ML

Abstract

During heart development, a subpopulation of cells in the heart field maintains cardiac potential over several days of development and forms the myocardium and smooth muscle of the arterial pole. Using clonal and explant culture experiments, we show that these cells are a stem cell population that can differentiate into myocardium, smooth muscle and endothelial cells. The multipotent stem cells proliferate or differentiate into different cardiovascular cell fates through activation or inhibition of FGF and BMP signaling pathways. BMP promoted myocardial differentiation but not proliferation. FGF signaling promoted proliferation and induced smooth muscle differentiation, but inhibited myocardial differentiation. Blocking the Ras/Erk intracellular pathway promoted myocardial differentiation, while the PLCgamma and PI3K pathways regulated proliferation. In vivo, inhibition of both pathways resulted in predictable arterial pole defects. These studies suggest that myocardial differentiation of arterial pole progenitors requires BMP signaling combined with downregulation of the FGF/Ras/Erk pathway. The FGF pathway maintains the pool of proliferating stem cells and later promotes smooth muscle differentiation.

MeSH Terms
Animals Arteries/cytology,growth & development,metabolism Body Patterning Bone Morphogenetic Protein 2/metabolism Cell Differentiation Cell Lineage Cell Proliferation Chick Embryo Fibroblast Growth Factor 8/metabolism Gene Expression Regulation, Developmental Heart/embryology MAP Kinase Signaling System Muscle, Smooth/cytology,embryology,metabolism Myocardium/cytology,metabolism Quail Stem Cells/cytology,metabolism Tissue Culture Techniques
Chemicals
Bone Morphogenetic Protein 2 Fibroblast Growth Factor 8
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hutson Mary Redmond
Division of Neonatology, Department of Pediatrics, Neonatal-Perinatal Research Institute, Box 103105, Duke University Medical Center, Durham, NC 27710, USA. mhutson@duke.edu
Zeng Xiaopei Lily
Kim Andrew J
Antoon Emily
Harward Stephen
Kirby Margaret L
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Article Info
Journal
Development (Cambridge, England)
Abbr.
Development
ISSN
1477-9129
DOI
10.1242/dev.051565
Email
mhutson@duke.edu
Published
2010-09-00
Epub
2010-00-11
Pages
3001-11
Language
English
Region
England
NLM ID
8701744
PMCID
PMC2926953
Subset
IM
Grants
NHLBI NIH HHS · R01 HL083240 · United States
NHLBI NIH HHS · R01 HL070140 · United States
NHLBI NIH HHS · HL070140 · United States
NHLBI NIH HHS · HL036059 · United States
NHLBI NIH HHS · HL083240 · United States
NHLBI NIH HHS · P01 HL036059 · United States
External Links
PubMed source DOI: 10.1242/dev.051565 PMC Full Text View journal details
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