Abstract
The process of valve formation is a tremendously complex process and involves a very intricate interplay between appropriate pathways at appropriate times. Although we have not completely elucidated the molecular pathways that lead to normal valve formation, we have identified a few major players in this process. We are now able to implicate TGF-ß, BMP, and NOTCH as suspects in tricuspid atresia (TA), as well as their downstream targets: NKX2-5, TBX5, NFATC1, GATA4, and SOX9. We know that the TGF-ß and the BMP pathways converge on the SMAD4 molecule, and we believe that this molecule plays a very important role to tie both pathways to TA. Similarly, we look at the NOTCH pathway and identify the HEY2 as a potential link between this pathway and TA. Another transcription factor that has been implicated in TA is NFATC1. While several mouse models exist that include part of the TA abnormality as their phenotype, no true mouse model can be said to represent TA. Bridging this gap will surely shed a lot of light on the molecular pathway on TA and allow us to fill in many gaps.
Original language | English |
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Title of host publication | Congenital Heart Diseases |
Subtitle of host publication | The Broken Heart: Clinical Features, Human Genetics and Molecular Pathways |
Publisher | Springer-Verlag Wien |
Pages | 591-605 |
Number of pages | 15 |
ISBN (Electronic) | 9783709118832 |
ISBN (Print) | 9783709118825 |
DOIs | |
Publication status | Published - 1 Jan 2015 |
Externally published | Yes |
Keywords
- AV canal
- Atrioventricular canal
- BMP
- EMT
- Epithelial-mesenchymal transition
- GATA4
- HEY2
- Looping
- Mesenchymal cells
- Mutant mice
- NFATC1
- NKX2-5
- NOTCH
- SMAD4
- SOX9
- TA
- TBX5
- TGF-ß
- Transforming growth factor
- Tricuspid atresia
- Trisomy 16
- Univentricular heart
- VEGF