Arterial pole progenitors interpret opposing FGF/BMP signals to proliferate or differentiate.
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.
Type
Journal articleSubject
AnimalsArteries
Body Patterning
Bone Morphogenetic Protein 2
Cell Differentiation
Cell Lineage
Cell Proliferation
Chick Embryo
Fibroblast Growth Factor 8
Gene Expression Regulation, Developmental
Heart
MAP Kinase Signaling System
Muscle, Smooth
Myocardium
Quail
Stem Cells
Tissue Culture Techniques
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https://hdl.handle.net/10161/4176Published Version (Please cite this version)
10.1242/dev.051565Publication Info
Hutson, MR; Zeng, XL; Kim, AJ; Antoon, E; Harward, S; & Kirby, ML (2010). Arterial pole progenitors interpret opposing FGF/BMP signals to proliferate or differentiate.
Development, 137(18). pp. 3001-3011. 10.1242/dev.051565. Retrieved from https://hdl.handle.net/10161/4176.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Stephen Harward
Assistant Professor of Neurosurgery
Mary Redmond Hutson
Assistant Professor of Pediatrics
My laboratory is interested in understanding how congenital heart defects occur. In
particular I am focused on defects of the conotruncus (or arterial pole) which include
persistent truncus arteriosus, double outlet right ventricle, and tetralogy of Fallot.
During early stages of heart development the secondary heart field, a population of
cardiac stem cells, forms the smooth muscle and myocardial junction of the arterial
pole. Another cell population important for arterial pole formation a
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