During vertebrate cardiac morphogenesis, pulmonary and systemic outflow structures are formed through division and reorganization of the embryonic truncus arteriosus. Over the past three years we have tested and helped to establish a new model of cardiac truncal septation. We have predicted and followed tissue movements in the developing chick truncus. Correlative studies of rat and human embryos have confirmed the existence and apparent motion, in the developing mammalian heart, of a structural septation complex which hold the developing valve sites in place and apart as the ventricular outflow tracts develop.
The specific aims of the proposed three year continuation of this research are to: 1) Map and illustrate relative tissue movements deeper in the heart, below the semilunar valves. 2) Characterize the ultrastructure and cytochemisry of the two attachment sites of mesenchymal condensations to the myocardial sleeve. 3) Extend current study of the patterns of DNA synthesis or cell-cycle synchrony along the myocardial sleeve. 4) Document changes in these indices of normal development following teratogenic insult. An independent study program in human cardiac development and neonatal cardiac pathology (10% of total effort) is proposed to: 1) Correlate cellular level events in human cardiac truncal septation with the results from animal studies, and 2) Educate the applicant in the anatomy of congenital defects in human cardiac outflow. The cardiac outflow structures under study are directly involved in about one-third of the congenital cardiac defects found in human infants. The long-range objective of our research remains unchanged: to describe normal and experimentally altered truncal development in detail sufficient to understand and eventually prevent such malformations.
