Genetic Wiring Diagram of the Cardiac Conduction System

In 1906, Tawara published his treatise, recently translated from German to English,1 on the anatomy of the cardiac conduction system, which he elucidated through painstaking dissection and histological examination. In the following decades, the conduction system was generally understood and studied in anatomic and physiological terms. Most molecular biology focused on the genes and proteins that generate or propagate the cardiac action potential. Unlike other tissues and organs, including the heart, little was known about its embryonic development, even though the anatomic form of the conduction system is clearly relevant to its function. Until recently, developmental biology was hampered by the lack of a working model of how the conduction system forms, reagents, and methods. This situation has changed significantly since Gourdie and Mikawa2 reported their seminal observations in 1995. In an elegant series of chick embryo experiments, their laboratories proved that a developing node or fiber in the central and peripheral conduction systems forms by recruitment of adjacent multipotent myocytes.2,3 The murine conduction system develops by the same process of accretion.4 Soon afterward, Berul et al,5 Morley et al,6 and Baker et al7 described their applications of intracardiac electrophysiology and optical mapping to study normal and abnormal conduction in the mouse, thus opening the door for experimental genetics and developmental biology.Article p 2535 The inductive patterning of tissues is a central theme in development. In the chick embryo, endothelin-1 is secreted by the coronary arterioles to induce …