Gene Regulatory Networks in Cardiac Conduction System Development

• Published in: Circulation research Vol. 110; no. 11; pp. 1525 - 1537
• Main Author: Munshi, Nikhil V
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 25.05.2012; Lippincott Williams & Wilkins
• Subjects: Animals; Atrioventricular Node - growth & development; Atrioventricular Node - metabolism; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Genotype; Heart Conduction System - embryology; Heart Conduction System - growth & development; Heart Conduction System - metabolism; Heart Conduction System - physiopathology; Heart Diseases - genetics; Heart Diseases - physiopathology; Humans; Phenotype; Purkinje Fibers - growth & development; Purkinje Fibers - metabolism; Sinoatrial Node - growth & development; Sinoatrial Node - metabolism; Transcription Factors - metabolism; Vertebrates: cardiovascular system; Vertebrata; Mammalia; Sinus node; Gene; Network; Development; Atrioventricular node; Circulatory system; Transcription factor; Purkinje fiber; Conduction system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.111.260026

The cardiac conduction system is a specialized tract of myocardial cells responsible for maintaining normal cardiac rhythm. Given its critical role in coordinating cardiac performance, a detailed analysis of the molecular mechanisms underlying conduction system formation should inform our understanding of arrhythmia pathophysiology and affect the development of novel therapeutic strategies. Historically, the ability to distinguish cells of the conduction system from neighboring working myocytes presented a major technical challenge for performing comprehensive mechanistic studies. Early lineage tracing experiments suggested that conduction cells derive from cardiomyocyte precursors, and these claims have been substantiated by using more contemporary approaches. However, regional specialization of conduction cells adds an additional layer of complexity to this system, and it appears that different components of the conduction system utilize unique modes of developmental formation. The identification of numerous transcription factors and their downstream target genes involved in regional differentiation of the conduction system has provided insight into how lineage commitment is achieved. Furthermore, by adopting cutting-edge genetic techniques in combination with sophisticated phenotyping capabilities, investigators have made substantial progress in delineating the regulatory networks that orchestrate conduction system formation and their role in cardiac rhythm and physiology. This review describes the connectivity of these gene regulatory networks in cardiac conduction system development and discusses how they provide a foundation for understanding normal and pathological human cardiac rhythms.