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Updated: May 16, 2026
Protein Isolation from the Developing Embryonic Mouse Heart Valve Region
Published on: September 23, 2014
Co-ordinating Notch, BMP, and TGF-β signaling during heart valve development
Victoria C Garside1, Alex C Chang, Aly Karsan
1Terry Fox Laboratory, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada.
Insights
Three key signaling pathways, BMP, TGF-β, and Notch, are crucial for heart valve development. Understanding these pathways in endothelial-to-mesenchymal transformation (EMT) can offer insights into congenital heart valve defects.
Area of Science:
- Developmental Biology
- Cardiovascular Research
- Molecular Signaling
Background:
- Congenital heart defects (CHDs) affect 1-5% of newborns, with 20-30% involving heart valve abnormalities.
- Understanding heart valve development is critical for addressing congenital valve defects and disease, given limited treatment options.
- Key factors regulating valve development are implicated in both congenital defects and acquired valve disease.
Purpose of the Study:
- To discuss the roles of BMP, TGF-β, and Notch signaling pathways in mouse cardiac cushion formation.
- To elucidate how these pathways coordinate endothelial-to-mesenchymal transformation (EMT) during heart valve development.
- To highlight the integration and cross-talk between these pathways in forming mature heart valves.
Main Methods:
- Review of current literature on signaling pathways in cardiac development.
- Focus on mouse models for studying cardiac cushion formation and valve development.
- Analysis of the interplay between BMP, TGF-β, and Notch signaling in EMT.
Main Results:
- BMP, TGF-β, and Notch signaling are essential for initiating and regulating endothelial-to-mesenchymal transformation (EMT) in cardiac cushions.
- BMPs from myocardium activate endocardium; Notch signaling initiates EMT.
- BMP and TGF-β signaling synergize with Notch to promote endothelial cell transition to mesenchyme and invasion.
Conclusions:
- The coordinated action of BMP, TGF-β, and Notch signaling pathways is fundamental for cardiac cushion formation and mesenchymal cell population.
- Integration and cross-talk among these pathways are vital for generating stratified heart valve leaflets and septa.
- This study provides insight into the molecular mechanisms underlying normal heart valve development and potential causes of congenital valve defects.
Abstract:
Congenital heart defects affect approximately 1-5 % of human newborns each year, and of these cardiac defects 20-30 % are due to heart valve abnormalities. Recent literature indicates that the key factors and pathways that regulate valve development are also implicated in congenital heart defects and valve disease. Currently, there are limited options for treatment of valve disease, and therefore having a better understanding of valve development can contribute critical insight into congenital valve defects and disease. There are three major signaling pathways required for early specification and initiation of endothelial-to-mesenchymal transformation (EMT) in the cardiac cushions: BMP, TGF-β, and Notch signaling. BMPs secreted from the myocardium set up the environment for the overlying endocardium to become activated; Notch signaling initiates EMT; and both BMP and TGF-β signaling synergize with Notch to promote the transition of endothelia to mesenchyme and the mesenchymal cell invasiveness. Together, these three essential signaling pathways help form the cardiac cushions and populate them with mesenchyme and, consequently, set off the cascade of events required to develop mature heart valves. Furthermore, integration and cross-talk between these pathways generate highly stratified and delicate valve leaflets and septa of the heart. Here, we discuss BMP, TGF-β, and Notch signaling pathways during mouse cardiac cushion formation and how they together produce a coordinated EMT response in the developing mouse valves.
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