Forkhead Transcription Factors, Foxc1 and Foxc2, Are Required for the Morphogenesis of the Cardiac Outflow Tract.
From: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, 332 PRB, 2220 Pierce Ave, Nashville, TN 37232-6300, USA.
Developmental biology
- Publish Date: Aug 2006
- ISSN: 0012-1606
- Volume: 296
- Issue: 2
- Pages: 421-36
- Medium: Print
- Language: English
- Citation (JAMA): Seo Seungwoon, Kume Tsutomu, et al. Forkhead Transcription Factors, Foxc1 and Foxc2, Are Required for the Morphogenesis of the Cardiac Outflow Tract.. Dev. Biol. Aug 2006;296:421-36
Abstract
Previous studies have shown that Foxc1 and Foxc2, closely related Fox transcription factors, have interactive roles in cardiovascular development. However, little is known about their functional overlap during early heart morphogenesis. Here, we show that Foxc genes are coexpressed in a novel heart field, the second heart field, as well as the cardiac neural crest cells (NCCs), endocardium, and proepicardium. Notably, compound Foxc1; Foxc2 mutants have a wide spectrum of cardiac abnormalities, including hypoplasia or lack of the outflow tract (OFT) and right ventricle as well as the inflow tract, dysplasia of the OFT and atrioventricular cushions, and abnormal formation of the epicardium, in a dose-dependent manner. Most importantly, in the second heart field, compound mutants exhibit significant downregulation of Tbx1 and Fgf8/10 and a reduction in cell proliferation. Moreover, NCCs in compound mutants show extensive apoptosis during migration, leading to a failure of the OFT septation. Taken together, our results demonstrate that Foxc1 and Foxc2 play pivotal roles in the early processes of heart development, especially acting upstream of the Tbx1-FGF cascade during the morphogenesis of the OFT.
Mesh Headings (Keywords): Animals, Cell Lineage, Female, Fibroblast Growth Factors, Forkhead Transcription Factors, Heart, Heart Ventricles, Mice, Mice, Knockout, Mutation, T-Box Domain Proteins, Ventricular Outflow Obstruction
Check for Full Text / PubMed Unique Identifier (PMID): 16839542
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