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Co-ordinating Notch, BMP, and TGF-β signaling during heart valve development
- Source :
- Cellular and Molecular Life Sciences. 70:2899-2917
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
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 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 signalling pathways required for early specification and initiation of Endothelial-to-Mesenchymal Transformation (EMT) in the cardiac cushions: BMP, TGFβ, and Notch signalling. BMPs secreted from the myocardium setup the environment for the overlying endocardium to become activated, Notch signalling initiates EMT, and both BMP and TGFβ signalling synergizes with Notch to promote the transition of endothelia to mesenchyme and to promote mesenchymal cell invasiveness. Together, these three essential signalling pathways help to 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, TGFβ, and Notch signalling pathways during mouse cardiac cushion formation and how they together produce a coordinated EMT response in the developing mouse valves.
- Subjects :
- Mesenchyme
Notch signaling pathway
Biology
Bone morphogenetic protein
Article
Cellular and Molecular Neuroscience
Transforming Growth Factor beta
medicine
Animals
Humans
Heart valve
Molecular Biology
Endocardium
Pharmacology
Receptors, Notch
Mesenchymal stem cell
Cell Biology
Anatomy
Transforming growth factor beta
Heart Valves
Cell biology
medicine.anatomical_structure
Bone Morphogenetic Proteins
embryonic structures
cardiovascular system
biology.protein
Molecular Medicine
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 14209071 and 1420682X
- Volume :
- 70
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Life Sciences
- Accession number :
- edsair.doi.dedup.....84442562217ee85ca0c0a2b124986682