ArticleJournal of molecular and cellular cardiology2012
The secondary heart field is a new site of calcineurin/Nfatc1 signaling for semilunar valve development.
Article in Journal of molecular and cellular cardiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- The second heart field: the first 20 years.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- NOTCH Signaling in Aortic Valve Development and Calcific Aortic Valve Disease.Frontiers in cardiovascular medicine · 2021Review
- Notch and interacting signalling pathways in cardiac development, disease, and regeneration.Nature reviews. Cardiology · 2018Review
- A Novel Mutation inFrontiers in cardiovascular medicine · 2017Article
- Endocardial-to-mesenchymal transformation and mesenchymal cell colonization at the onset of human cardiac valve development.Development (Cambridge, England) · 2016Article
- Embryonic Development of the Bicuspid Aortic Valve.Journal of cardiovascular development and disease · 2015Article
- Cadherin-11 coordinates cellular migration and extracellular matrix remodeling during aortic valve maturation.Developmental biology · 2015Article
- Nfatc1 directs the endocardial progenitor cells to make heart valve primordium.Trends in cardiovascular medicine · 2013Review
- Molecular and cellular aspects of calcific aortic valve disease.Circulation research · 2013Review
- Cardiac outflow tract anomalies.Wiley interdisciplinary reviews. Developmental biology · 2013Review
- ENU-induced mutation in the DNA-binding domain of KLF3 reveals important roles for KLF3 in cardiovascular development and function in mice.PLoS genetics · 2013Article
- Partitioning the heart: mechanisms of cardiac septation and valve development.Development (Cambridge, England) · 2012Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Semilunar valve malformations are common human congenital heart defects. Bicuspid aortic valves occur in 2-3% of the population, and pulmonic valve stenosis constitutes 10% of all congenital heart disease in adults (Brickner et al., 2000) [1]. Semilunar valve defects cause valve regurgitation, stenosis, or calcification, leading to endocarditis or congestive heart failure. These complications often require prolonged medical treatment or surgical intervention. Despite the medical importance of valve disease, the regulatory pathways governing semilunar valve development are not entirely clear. In this report we investigated the spatiotemporal role of calcineurin/Nfatc1 signaling in semilunar valve development. We generated conditional knockout mice with calcineurin gene disrupted in various tissues during semilunar valve development. Our studies showed that calcineurin/Nfatc1 pathway signals in the secondary heart field (SHF) but not in the outflow tract myocardium or neural crest cells to regulate semilunar valve morphogenesis. Without SHF calcineurin/Nfatc1 signaling, the conal endocardial cushions-the site of prospective semilunar valve formation--first develop and then regress due to apoptosis, resulting in a striking phenotype with complete absence of the aortic and pulmonic valves, severe valve regurgitation, and perinatal lethality. This role of calcineurin/Nfatc1 signaling in the SHF is different from the requirement of calcineurin/Nfatc1 in the endocardium for semilunar valve formation (Chang et al., 2004) [2], indicating that calcineurin/Nfatc1 signals in multiple tissues to organize semilunar valve development. Also, our studies suggest distinct mechanisms of calcineurin/Nfat signaling for semilunar and atrioventricular valve morphogenesis. Therefore, we demonstrate a novel developmental mechanism in which calcineurin signals through Nfatc1 in the secondary heart field to promote semilunar valve morphogenesis, revealing a new supportive role of the secondary heart field for semilunar valve formation.
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