Arterial pole progenitors interpret opposing FGF/BMP signals to proliferate or differentiate.
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.
Hutson
Mary Redmond
MR
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
XL
Kim
Andrew J
AJ
Antoon
Emily
E
Harward
Stephen
S
Kirby
Margaret L
ML
D000818:Animals; D001158:Arteries / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D019521:Body Patterning; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002642:Chick Embryo; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology; D020935:MAP Kinase Signaling System; D009130:Muscle, Smooth / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011784:Quail; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D046509:Tissue Culture Techniques
D055396:Bone Morphogenetic Protein 2; D051524:Fibroblast Growth Factor 8