Development of the Cardiac Conduction System as Delineated by minK‐lacZ

INTRODUCTION: Due to the lack of good molecular markers, for decades the morphogenetic origin of the cardiac conduction system has been a matter of debate. More recently, the spatial expression of minK-lacZ in the adult mouse heart has been shown, for the larger part, to be coincident with the conduction tissues. METHODS AND RESULTS: To trace the embryonic development of this system, we performed an analysis of the expression of this construct throughout early cardiac development. Expression was first seen at the eighth embryonic day. Subsequently, discrete rings were found at the sinuatrial, atrioventricular, interventricular, and ventriculoarterial junctions. With time, the expression became restricted to boundary regions of the heart, such as the hinges of the leaflets of the pulmonary and aortic valves, the atrioventricular rings, and the venous valves, as well as becoming incorporated into the definitive conduction tissues themselves. In the postnatal heart, the areas retaining minK-lacZ positivity outside of the definitive conduction tissues are known to be the site of origin of abnormal cardiac rhythms, suggesting that ectopic foci may derive from tissues that share a common developmental pathway with the definitive conduction system. CONCLUSION: Our findings suggest that the boundary regions between compartments, along with the atrioventricular conduction axis, share a common developmental pathway.