Teed Off Cardiac Conduction System Development Requires T-box Transcription Factors

In this issue of Circulation Research, Bakker et al1 reportthat the T-box transcription factor Tbx3 is required for development of the mouse atrioventricular conduction sys-tem. This study adds to the increasingly complex roles for T-box genes in the regulation of cell lineage maturation and proliferation in the developing heart. Previous studies from this same group have implicated Tbx3 in control of mouse sinoatrial node development and pacemaker activity.2 A closely related factor Tbx2 also contributes to atrioventricular (AV) canal specification by repressing genes expressed in the chamber myocardium.3,4 Mutations in human TBX5 cause Holt–Oram syndrome, which includes conduction system disease, and mice with heterozygous mutations in Tbx5 develop progressive AV block and other conduction anomalies.5–7 Additional T-box factors including Tbx1, Tbx20, and Tbx18 are expressed in distinct compartments of the heart and have critical functions i