Patterning and Development of the Conduction System of the Heart: Origins of the Conduction System in Development

This chapter focuses on the cellular origin of the conduction system components and the molecular genetic mechanisms that may control their phenotype and position within the developing heart. It discusses the connection between heart cell precursor pools, which in a temporal pattern form the heart, and the genesis of the conduction system components. The distinct components of the cardiac conduction system of the heart are essentially myocardial. They are innervated by cardiac ganglia largely derived from neural crest. In addition, a large fraction of cells in the mature conduction system is noncardiac, and insulating layers of fibrous tissue are found around conduction system components, such as the SAN and AV bundle. These noncardiac cell types are derived from the epicardium (fibroblasts), endocardium, neural crest (neural innervations), and other sources, although their origins have not been defined in detail. Although these nerves and fibrous tissues are important, or even a prerequisite, for conduction system formation and function, the cardiomyocytes are essential for impulse generation and propagation. Furthermore, in the embryo the functional myocardial conduction system is not yet innervated and interstitial fibroblast and fibrous tissues in association with the conduction system are sparse or absent. Studies of the development of the conduction system components strongly suggest that they originate from myocardial precursors, which in turn are derived from mesoderm and pericardial wall mesenchyme.