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

• Published in: Cardiovascular research Vol. 65; no. 3; pp. 711 - 718
• Main Authors: KANZAKI-KATO, Naoko, TAMAKOSHI, Tomoki, MIURA, Naoyuki, YAN FU, CHANDRA, Abhishek, ITAKURA, Tatsuo, UEZATO, Tadayoshi, TANAKA, Toshinobu, CLOUTHIER, David E, SUGIYAMA, Toshihiro, YANAGISAWA, Masashi
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.02.2005
• Subjects: Animals; Aorta, Thoracic - abnormalities; Aorta, Thoracic - embryology; Biological and medical sciences; Body Patterning - physiology; Cardiology. Vascular system; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; Fetal Death - genetics; Forkhead Transcription Factors; Gene Expression Regulation, Developmental - physiology; Genotype; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; In Situ Hybridization; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Receptor, Endothelin A - genetics; Receptor, Endothelin A - metabolism; Receptor, Endothelin A - physiology; Reverse Transcriptase Polymerase Chain Reaction - methods; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology; Truncus Arteriosus, Persistent - genetics; Heart failure; Developmental biology; Cardiovascular disease; Biology; Endothelin 1; Gene expression; Artery; Arteries; Morphogenesis; Foxc2; Heart disease; Transcription factor; Biological receptor
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/j.cardiores.2004.10.017

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.