Monitoring Clonal Growth in the Developing Ventricle

Understanding the etiology of congenital heart defects depends on a detailed knowledge of the morphogenetic events underlying cardiac development. Deciphering the developmental processes and cell behaviors resulting in the formation of a four-chambered heart requires techniques by which the destiny of individual cells can be traced during development. Ideally, such approaches provide information on progenitor cells and growth properties of clonally related myocytes. In the avian system, clonal analysis based on the use of replication-defective retroviral labeling led to a model for growth of the ventricular wall from polyclonal transmural cones of myocardial cells. In the mouse, the nlaacZ retrospective clonal analysis system has proved to be a powerful technique for studying different aspects of cardiac morphogenesis. Morphologic and histologic analyses of clonally related myocytes at early stages of development have provided genetic evidence for the formation of the heart tube from two cell lineages. Additional aspects of cardiac morphogenesis, including formation of the interventricular septum and myocardial outflow tract, and more recently, the origin of the ventricular conduction system, have been studied using this system. This brief review discusses how the nlaacZ system has provided new insights into the divergent properties of clonally related cells in these different regions of the developing heart.