Coronary arteriogenesis and differentiation of periarterial Purkinje fibers in the chick heart: is there a link?

Abstract

In the following review, we outline the cellular ontogeny and time course of coronary artery development within the vertebrate heart. Our eventual focus will be the potential role of arteriogenesis in the differentiation of a subset of specialized conduction cells in the chick heart. We begin by briefly outlining early heart formation, showing how the outermost layer of the looped, tube heart--the epicardium--is of extracardiac origin and provides the progenitor cells to the entire vascular bed. Subsequently, we summarize the events of coronary arterial development that follow epicardialization. Finally, we discuss work in the chick that indicates how arteries form pioneering, directional conduits through ventricular tissue, adjacent to which myocardial cells differentiate to form the most peripheral component of the avian conduction system--a network of periarterial Purkinje fibers.

Fig. 1 Basic structural and functional organization of the embryonic pacemaking and conduction system. The organization of the conduction system in the avian heart is similar to its mammalian counterpart. Central conduction system elements include the sinoatrial node (SA node) or pacemaker, the atrioventricular ring (AV ring) and atrioventricular node (AV node), and bundle of His. The peripheral conduction system components are the left and right septal bundle branches, subendocardial Purkinje fibers, and periarterial Purkinje fibers. The description of periarterial Purkinje fibers in the chick is, to date, species specific, and no such fibers have been identified in the mammalian system thus far. In both mammals and avians, the subendocardial region contains subendocardial Purkinje fibers and is functionally distinct from the working myocardium.

Fig. 2 Basic structural and functional organization of the embryonic pacemaking and conduction system. The model shown in the left-hand panel is based on the embryonic chick heart. In the chick, the terminal-most component of the conduction system penetrates into the ventricular muscle in intimate association with the coronary arteries. The periarterial Purkinje fiber (PPF) shown enlarged in the right-hand panel has been simultaneously labeled for 3 markers of conduction lineage: a gap junction protein connexin40 (Cx40, yellow); a myosin heavy chain (sMHC, green); and Nkx-2.5 (red), a transcription factor. The endothelial cells lining the artery also contain Cx40 gap junctions.

Fig. 3 Induction of periarterial Purkinje fiber (ppf) conduction cells. The left-hand panel shows a cluster of red nuclei delineating a clone of lacZ-expressing cells infected with a defective retrovirus. The clone contains both working myocytes and an sMHC+ (green) Purkinje fiber—a pattern consistent with the occurrence of localized recruitment of a multipotent progenitor cell to specialized myocardial lineages in the avian heart. The right-hand panel shows a model in which hemodynamically induced factors (for example, endothelin-1) from arterial tissues locally mediate this divergence into either working myocytes or Purkinje fiber conduction cells within a cardiomyogenic lineage.

Fig. 4 A model for the molecular induction of Purkinje fiber conduction cells. The site of specific cleavage of bigET-1 by ECE-1 may be a mechanism by which localized induction of conduction cells occurs.