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(Circulation Research. 2009;105:620.)
© 2009 American Heart Association, Inc.

Review

Specification of the Cardiac Conduction System by Transcription Factors

Cathy J. Hatcher, Craig T. Basson

From the Center for Molecular Cardiology; Greenberg Division of Cardiology; Weill Medical College of Cornell University; 1300 York Avenue, New York, NY 10065.

Correspondence to Corresponding author: Cathy J. Hatcher, PhD, Center for Molecular Cardiology, Greenberg Division of Cardiology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065. E-mail cjhatche{at}med.cornell.edu

This Review is part of a thematic series on Developmental Biology, which includes the following articles:

Signaling Pathways Controlling Second Heart Field Development [2009;104:933–942]

Heart Valve Development: Regulatory Networks in Development and Disease [2009;105:408–421]

Specification of the Cardiac Conduction System by Transcription Factors

Origin of Cardiac Fibroblasts and the Role of Periostin

Conduction System Specification

Coronary Artery Development-Myocardial Vessel Interaction

Myocyte Development-Specification/Epicardium
Elizabeth McNally Guest Editor

Abstract: Diseases of the cardiovascular system that cause sudden cardiac deaths are often caused by lethal arrhythmias that originate from defects in the cardiac conduction system. Development of the cardiac conduction system is a complex biological process that can be wrought with problems. Although several genes involved in mature conduction system function have been identified, their association with development of specific subcomponents of the cardiac conduction system remains challenging. Several transcription factors, including homeodomain proteins and T-box proteins, are essential for cardiac conduction system morphogenesis and activation or repression of key regulatory genes. In addition, several transcription factors modify expression of genes encoding the ion channel proteins that contribute to the electrophysiological properties of the conduction system and govern contraction of the surrounding myocardium. Loss of transcriptional regulation during cardiac development has detrimental effects on cardiogenesis that may lead to arrhythmias. Human genetic mutations in some of these transcription factors have been identified and are known to cause congenital heart diseases that include cardiac conduction system malformations. In this review, we summarize the contributions of several key transcription factors to specification, patterning, maturation, and function of the cardiac conduction system. Further analysis of the molecular programs involved in this process should lead to improved diagnosis and therapy of conduction system disease.

Key Words: cardiac development • cardiac conduction system • transcription factors • arrhythmia