doi: 10.1161/CIRCRESAHA.109.193680
© 2009 American Heart Association, Inc.
Editorials |
Setting the Pace
Tbx3 and Tbx18 in Cardiac Conduction System Development
From the Section of Cardiology, University of Chicago, Ill.
Correspondence to Elizabeth M. McNally, 5841 S Maryland, MC6088, Chicago, IL 60637. E-mail emcnally@uchicago.edu
See related articles, pages 388–397
Key Words: Tbox genes • Tbx3 • Tbx18 • cardiac conduction • pacemaker
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
A vexing problem for clinicians in the management of children and adults with congenital heart disease is the management of the accompanying arrhythmias. In the recent decade, the mutational spectrum associated with human congenital heart disease has begun to come into focus.1 The number of distinct genes implicated in human congenital heart disease is considerable, and a large portion of mutated genes encode transcription factors. Autosomal dominant mutations in NKX2.5 associate with primarily atrial septal defects, but importantly these defects are distinguished by the presence of atrioventricular nodal defects including heart block. The Holt–Oram syndrome, or heart–hand syndrome, arises from dominant mutations in Tbx5, a member of the brachyury family of transcription factors and is also associated with the development of atrioventricular nodal disease. Further investigation of these genes using mouse genetic models has begun to refine the detailed program required for development of specific components of the cardiac conduction system.
The mammalian cardiac conduction system is composed of the sinoatrial (SA) node, the atrioventricular node, the His bundle, the left and right bundle branches, and the ventricular Purkinje fibers. For many of these components, transcriptional regulators have been identified that are critical for their proper development or maintenance (see Figure). Nkx2.5 is required for the development and maintenance of the atrioventricular node.2 In addition, the development of the atrioventicular node is also dependent on Tbx5 and Id2, whereas the distal ventricular conduction system requires Id2 and HOP.3,4 The precise delineation and maintenance of the conduction system likely requires
Related Article:
Circ. Res. 2009 104: 388-397.