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

dc.contributor.author

Hutson, MR

dc.contributor.author

Zeng, XL

dc.contributor.author

Kim, AJ

dc.contributor.author

Antoon, E

dc.contributor.author

Harward, S

dc.contributor.author

Kirby, ML

dc.coverage.spatial

England

dc.date.accessioned

2011-06-21T17:27:31Z

dc.date.issued

2010-09

dc.description.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.

dc.description.version

Version of Record

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/20702561

dc.identifier

dev.051565

dc.identifier.eissn

1477-9129

dc.identifier.uri

https://hdl.handle.net/10161/4176

dc.language

eng

dc.language.iso

en_US

dc.publisher

The Company of Biologists

dc.relation.ispartof

Development

dc.relation.isversionof

10.1242/dev.051565

dc.relation.journal

Development

dc.subject

Animals

dc.subject

Arteries

dc.subject

Body Patterning

dc.subject

Bone Morphogenetic Protein 2

dc.subject

Cell Differentiation

dc.subject

Cell Lineage

dc.subject

Cell Proliferation

dc.subject

Chick Embryo

dc.subject

Fibroblast Growth Factor 8

dc.subject

Gene Expression Regulation, Developmental

dc.subject

Heart

dc.subject

MAP Kinase Signaling System

dc.subject

Muscle, Smooth

dc.subject

Myocardium

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Quail

dc.subject

Stem Cells

dc.subject

Tissue Culture Techniques

dc.title

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

dc.title.alternative
dc.type

Journal article

duke.date.pubdate

2010-9-15

duke.description.issue

18

duke.description.volume

137

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/20702561

pubs.begin-page

3001

pubs.end-page

3011

pubs.issue

18

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Duke

pubs.organisational-group

Pediatrics

pubs.organisational-group

Pediatrics, Neonatology

pubs.organisational-group

School of Medicine

pubs.publication-status

Published

pubs.volume

137

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