Journal
CIRCULATION RESEARCH
Volume 110, Issue 11, Pages 1513-1524Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.112.265041
Keywords
Iroquois homeobox; cardiac transcription factor; cardiac development
Funding
- Heart and Stroke Foundation (HSF) of Ontario [T6485]
- Canadian Institutes of Health Research
- National Institutes of Health/National Heart, Lung, and Blood Institute [R01 HL93414 ARRA]
- Lawrence J. and Florence A. DeGeorge Charitable Trust/American Heart Association
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Numerous cardiac transcription factors play overlapping roles in both the specification and proliferation of the cardiac tissues and chambers during heart development. It has become increasingly apparent that cardiac transcription factors also play critical roles in the regulation of expression of many functional genes in the prenatal and postnatal hearts. Accordingly, mutations of cardiac transcription factors cannot only result in congenital heart defects but also alter heart function thereby predisposing to heart disease and cardiac arrhythmias. In this review, we summarize the roles of Iroquois homeobox (Irx) family of transcription factors in heart development and function. In all, 6 Irx genes are expressed with distinct and overlapping patterns in the mammalian heart. Studies in several animal models demonstrate that Irx genes are important for the establishment of ventricular chamber properties, the ventricular conduction system, as well as heterogeneity of the ventricular repolarization. The molecular mechanisms by which Irx proteins regulate gene expression and the clinical relevance of Irx functions in the heart are discussed. (Circ Res. 2012;110:1513-1524.)
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