BMP and FGF regulatory pathways control cell lineage diversification of heart valve precursor cells. Dev Biol 2006 Apr 15;292(2):292-302
Date
05/09/2006Pubmed ID
16680829DOI
10.1016/j.ydbio.2005.12.042Scopus ID
2-s2.0-33646924001 (requires institutional sign-in at Scopus site) 99 CitationsAbstract
The atrioventricular heart valve leaflets and chordae tendineae are composed of diverse cell lineages and highly organized extracellular matrices that share characteristics with cartilage and tendon cell types in the limb buds and somites. During embryonic chicken valvulogenesis, aggrecan and sox9, characteristic of cartilage cells, are observed in the AV valve leaflets, in contrast to tendon-associated genes scleraxis and tenascin, present in the chordae tendineae. In the limb buds and somites, cartilage cell lineage differentiation is regulated by BMP2, while FGF4 controls tendon cell fate. The ability of BMP2 and FGF4 to induce similar patterns of gene expression in heart valve precursor cells was examined. In multiple assays of cells from prefused endocardial cushions, BMP2 is sufficient to activate Smad1/5/8 phosphorylation and induce sox9 and aggrecan expression, while FGF4 treatment increases phosphorylated MAPK (dpERK) signaling and promotes expression of scleraxis and tenascin. However, these treatments do not alter differentiated lineage gene expression in valve progenitors from fused cushions of older embryos. Together, these studies define regulatory pathways of AV valve progenitor cell diversification into leaflets and chordae tendineae that share inductive interactions and differentiation phenotypes with cartilage and tendon cell lineages.
Author List
Lincoln J, Alfieri CM, Yutzey KEAuthor
Joy Lincoln PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBone Morphogenetic Protein 2
Bone Morphogenetic Proteins
Cell Differentiation
Cell Lineage
Cells, Cultured
Chick Embryo
Collagen
Drug Combinations
Fibroblast Growth Factor 4
Gene Expression Regulation, Developmental
Heart Valves
Immunohistochemistry
In Situ Hybridization
Laminin
Proteoglycans
Reverse Transcriptase Polymerase Chain Reaction
Stem Cells
Transforming Growth Factor beta