Spatiotemporal pattern of commitment to slowed proliferation in the embryonic mouse heart indicates progressive differentiation of the cardiac conduction system

Patterns of DNA synthesis in the developing mouse heart between ED7.5-18.5 were studied by a combination of thymidine and bromodeoxyuridine labeling techniques. From earliest stages, we found zones of slow myocyte proliferation at both the venous and arterial poles of the heart, as well as in the atrioventricular region. The labeling index was distinctly higher in nonmyocardial populations (endocardium, epicardium, and cardiac cushions). Ventricular trabeculae showed lower proliferative activity than the ventricular compact layer after their appearance at ED9.5. Low labeling was observed in the pectinate muscles of the atria from ED11.5. The His bundle, bundle branches, and Purkinje fiber network likewise were distinguished by their lack of labeling. Thymidine birthdating (label dilution) showed that the cells in these emerging components of the cardiac conduction system terminally differentiated between ED8.5-13.5. These patterns of slowed proliferation correlate well with those in other species, and can serve as a useful marker for the forming conduction system. (C) 2003 Wiley-Liss, Inc.