Developmental Origin of the Cardiac Conduction System: Insight from Lineage Tracing

The components of the cardiac conduction system (CCS) generate and propagate the electrical impulse that initiates cardiac contraction. These interconnected components share properties, such as automaticity, that set them apart from the working myocardium of the atria and ventricles. A variety of tools and approaches have been used to define the CCS lineages. These include genetic labeling of cells expressing lineage markers and fate mapping of dye labeled cells, which we will discuss in this review. We conclude that there is not a single CCS lineage, but instead early cell fate decisions segregate the lineages of the CCS components while they remain interconnected. The latter is relevant for development of therapies for conduction system disease that focus on reprogramming cardiomyocytes or instruction of pluripotent stem cells.