Roles of forkhead transcription factor Foxc2 (MFH-1) and endothelin receptor a in cardiovascular morphogenesis

Naoko Kanzaki-Kato, Tomoki Tamakoshi, Yan Fu, Abhishek Chandra, Tatsuo Itakura, Tadayoshi Uezato, Toshinobu Tanaka, David E. Clouthier, Toshihiro Sugiyama, Masashi Yanagisawa, Naoyuki Miura

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Foxc2/MFH-1 is a member of the forkhead family of transcription factors and Foxc2-deficient mice exhibit aortic arch anomalies (type B interruption of the aortic arch). Endothelin receptor type-A (ETA) is one of the two known endothelin receptors that belong to the G-protein-coupled receptor family. ETA-deficient mice show defects in the great arteries, primarily type B interruption of the aortic arch. Based on similar phenotypes in the cardiovascular system of Foxc2- and ETA-deficient mice, we investigated whether Foxc2 and ETA have a close relationship in aortic arch patterning. The Foxc2 and ETA homozygotes were obtained by crossing the Foxc2 and ETA heterozygotes, respectively. The double Foxc2/ETA homozygotes were obtained by crossing the double Foxc2/ETA heterozygotes. We investigated the expression of ETA in Foxc2-null mice and the expression of Foxc2 in ETA-null mice and found that the absence of either Foxc2 or ETA had no effect on the expression of the other. Next, we analyzed mice lacking both Foxc2 and ETA to examine the relationship between Foxc2 and ETA on aortic arch patterning in vivo. We found that the majority of Foxc2/ETA double-mutant embryos died around 11.5 dpc and that all surviving mice had persistent truncus arteriosus. The results suggest that Foxc2- and ETA-expressing cells additively form the aorticopulmonary septum.

Original languageEnglish (US)
Pages (from-to)711-718
Number of pages8
JournalCardiovascular research
Issue number3
StatePublished - Feb 15 2005


  • Arteries
  • Developmental biology
  • Foxc2
  • Gene expression
  • Heart failure

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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