One of the most fascinating aspects in the formation of the heart is the very early development of the electrical patterning as can be registered by the ECG, which is the registration of the rhythmic waves of depolarizing activity over the cardiac muscle. In the mature heart, the conduction system is held responsible for the rhythmic excitations and contractions. However, in chicken embryos a sinusoidal type of ECG can already be derived from the linear heart tube stages at about two days of development onward, and less than one day later when chamber formation has just been initiated, an adult type of ECG can be monitored. The presence of an adult type of ECG in these early embryonic hearts betrays the development of fast-conducting chambers rather than the presence of a conduction system. We now know that the primary heart tube as seen in the early embryo contains the precursors for the left ventricle only, or even less, 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 during further development from a single center of growth outside the heart. Therefore, it is impossible that the straight heart tube contains the precursors for the conduction system as rings separating the purported cardiac segments. 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. The transcriptional repressors Tbx2 and Tbx3 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. The cardiac building plan and the underlying mechanisms of its formation are conserved from fish to man. Detailed reconstructions of the developmental patterns of expression of Tbx3 during development in mouse and human have revealed, that Tbx3 is expressed in those areas of the heart tube that do not become chamber, i.e. in the sinu-nodal region, internodal region, atrioventricular junction, atrioventricular bundle and bundle branches. These areas comprise not only the conventional conduction system, but also the highly controversial areas of the internodal region and the entire atrioventricular junction. Also the (right) ventricular outflow tract initially expresses these transcriptional repressors, preventing it from chamber differentiation. These observations provide an embryonic basis why some areas in the heart are more arrhythmogenic than other regions.

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