Spatial distribution of “tissue-specific” antigens in the developing human heart and skeletal muscle III. An immunohistochemical analysis of the distribution of the neural tissue antigen G1N2 in the embryonic heart; implications for the development of the atrioventricular conduction system



A monoclonal antibody raised against an extract from the Ganglion Nodosum of the chick and designated GIN2 proves to bind specifically to a subpopulation of cardiomyocytes in the embryonic human heart. In the youngest stage examined (Carnegie stage 14, i. e., 4 1/2 weeks of development) these GIN2-expressing cells are localized in the myocardium that surrounds the foramen between the embryonic left and right ventricle. In the lesser curvature of the cardiac loop this “primary” ring occupies the lower part of the wall of the atrioventricular canal. During subsequent development, GIN2-expressing cells continue to identify the entrance to the right ventricle, but the shape of the ring changes as a result of the tissue remodelling that underlies cardiac septation. During the initial phases of this process the staining remains recognizable as a continuous band of cells in the myocardium that surrounds the developing right portion of the atrioventricular canal, subendocardially in the developing interventricular septum and around the junction of the embryonic left ventricle with the subaortic portion of the outflow tract. During the later stages of cardiac septation, the latter part of the ring discontinues to express GIN2, while upon the completion of septation, no GIN2-expressing cardiomyocytes can be detected anymore. The topographic distribution pattern of GIN suggests that the definitive ventricular conduction system derives from a ring of cells that initially surrounds the “primary” interventricular foramen. The results indicate that the atrioventricular bundle and bundle branches develop from GIN2-expressing myocytes in the interventricular septum, while the “compact” atrioventricular node develops at the junction of the band of GIN2-positive cells in the right atrioventricular junction (the right atrioventricular ring bundle) and the (“pentrating”) atrioventricular bundle. A “dead-end tract” represents remnants of conductive tissue in the anterior part of the top of the interventricular septum. The location of the various components of the avian conduction system is topographically homologous with that of the GIN2-ring in the human embryonic heart, indicating a phylogentically conserved origin of the conduction system in vertebrates.