The cardiac pacemaker and conduction system develops from embryonic myocardium that retains its primitive phenotype.

Disorders of the cardiac conduction system occur frequently and may cause life-threatening arrhythmias requiring medication or electronic pacemaker implantation. Repair or regeneration of conduction system components is currently not possible due to limited knowledge of the molecular regulation of pacemaker myocardium. Origin and development of the cardiac conduction system have been subject to debate for many decades. This review will discuss recent advances in our understanding of the molecular regulation of the development of the conduction system. We conclude that the components of the cardiac conduction system originate from embryonic myocardium that has maintained essential features of its primitive phenotype, whereas the adjacent myocardium differentiates into working myocardium.