The role of neural crest and epicardium-derived cells in conduction system formation.

During cardiac development the heart tube loops and is septated into a four-chambered structure. The initial peristaltic contraction of the primitive myocardium is replaced by a system of working myocardium and a myocardial-derived central and peripheral conduction system. The genes guiding this differentiation process are still under investigation and it has yet to be decided whether we are dealing with a recruitment or a specification model. We have shown that the complicated looping process of the heart tube brings together the essential parts of the sinoatrial and primary ring myocardium, that are the embryonic precursors of the definitive conduction system. From our studies it is evident that during development there are sinoatrial tracts that run between the sinoatrial and the atrioventricular node as well as tracts surrounding the pulmonary veins and the coronary sinus. Furthermore, we show that both in the chicken and mouse embryo neural crest cells reach the confinement of the central conduction system through the inflow and outflow tract. For the Purkinje system there is a close approximation with the epicardium-derived cells. We postulate that both extracardiac-derived cell types have an influence on the differentiation of the definitive conduction system.