The Development of the Ventricular Conduction System: Transgenic Insights

Summary

Over the last century, extensive literature has been devoted to the understanding of the origin of the cardiac conduction system. First descriptions suggested that the ventricular conduction has a myocardial origin, although more recently this common wisdom was challenged by the fact that several neural markers are specifically expressed in the developing conduction system, leading to the hypothesis of an extracardiac origin. Cell tracing experiments in chicken embryos have recently demonstrated a myocardial origin for several components of the ventricular conduction system, i.e. peripheral Purkinje network, although the origin of the bundle branches and the atrioventricular node remain controversial.

During the last years, the analysis of the transcriptional potential of truncated cis-acting elements of several gene loci have provided transgenic lines with restricted (compartment-specific) expression during cardiac development that can shed light into the developmental origin of distinct regions of the heart. A truncated human desmin promoter and a KCNE1 knock-in transgene show that β-galactosidase expression is confined to the ventricular conduction system in the fetal/adult stage. In this study we have investigated the early expression profile of these two transgenic lines and compared them with the endogenous gene expression. Analyses of desmin transgenics reveal that myocardial cells from the early straight tube contribute to the atrioventricular node and the bundle branches, whereas KCNE1 -transgenics reveal a substantial contribution of the interventricular ring to those structures. These data reinforce the notion that the atrioventricular node and bundle of His have a myocardial origin.