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In the hearts of mammals and birds, a system of nodes and fast-conducting tissues govern the activation pattern that induces myocardial contractions. We have previously shown that the atrioventricular conduction axis, consisting of the atrioventricular junction and the ventricles, is evolutionary conserved. From fish to man, the embryonic heart is patterned into compartments by the same genes. It has a muscular and slow conducting atrioventricular canal (Tbx2/3 positive) and a spongy ventricle (Cx40 and Anf positive) that serves the dual purpose of fast conduction and contraction. This design is maintained in fishes, amphibians and reptiles, whereas mammals and birds develop a fibrous insulating plane, thick compact ventricular walls and septum and, hence, form a discrete ventricular (His-Purkinje) conduction system from the embryonic spongy ventricle. Our understanding of the cardiac pacemaker, seen as a sinus node in mammals, is less clear. Most vertebrates have myocardium upstream of the right atrium (atrium in fishes) called the sinus venosus. It remains disputed if the dominant pacemaker of the heart is a property of the sinus venosus in entirety or of a specialised subset of sinus venosus myocardium. In the anole lizard the sinus venosus consists of three sinus horns that together equal the size of the right atrium. We investigated the electrical activation of the sinus venosus with optical mapping. Activation was earliest in the posterior sinus horn and then spread to the anterior sinus horns both of which are guarded by valves at the sinus-venous border. Later, the atria were activated from the dorsal sinu-atrial border, where the sinus node of mammals and birds is located. This region expressed the conserved sinus node markers Isl1 and Tbx3. We conclude that chambers and border regions of the vertebrate heart have highly similar patterns of gene expression and phenotypes, and that the cardiac conduction system simply follows from this building plan. Consequently, modifications rather than novelties characterise cardiac evolution. [ABSTRACT FROM AUTHOR]

Molecular and genetic studies around the turn of this century have revolutionized the field of cardiac development. We now know that the primary heart tube, as seen in the early embryo contains little more than the precursors for the left ventricle, whereas the precursor cells for the remainder of the cardiac components are continuously added, to both the venous and arterial pole of the heart tube, from a single centre of growth outside the heart. While the primary heart tube is growing by addition of cells, it does not show significant cell proliferation, until chamber differentiation and expansion starts locally in the tube, by which the chambers balloon from the primary heart tube. The transcriptional repressors Tbx2 andTbx3 locally repress the chamber-specific program of gene expression, by which these regions are allowed to differentiate into the distinct components of the conduction system. Molecular genetic lineage analyses have been extremely valuable to assess the distinct developmental origins of the various component parts of the heart, which currently can be unambiguously identified by their unique molecular phenotype. [ABSTRACT FROM AUTHOR]