Forkhead transcription factors, Foxc1 and Foxc2, are required for the morphogenesis of the cardiac outflow tract

Seungwoon Seo, Tsutomu Kume*

*Corresponding author for this work

Research output: Contribution to journalArticle

96 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)421-436
Number of pages16
JournalDevelopmental Biology
Volume296
Issue number2
DOIs
StatePublished - Aug 15 2006

Keywords

  • Cushion mesenchyme
  • Epicardium
  • Forkhead
  • Heart development
  • Neural crest
  • Outflow tract
  • Second heart field

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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