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Foxc1, Foxc2 and morphogenesis of the cardiac outflow tract

PostPosted: Wed Sep 20, 2006 8:41 pm
by patoco
Forkhead transcription factors, Foxc1 and Foxc2, are required for the morphogenesis of the cardiac outflow tract.

Seo S, Kume T.
Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt
University Medical Center, 332 PRB, 2220 Pierce Ave, Nashville, TN
37232-6300, USA.

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

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.

PMID: 16839542 [PubMed - as supplied by publisher] ... med_docsum


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