Heart development will be studied in normal and cardiac lethal mutant salamanders and in cardiomyopathic hamsters by using immunohistochemical, electrophysiology, biochemical, electron microscopic, radioimmunoassay and tissue/organ culture methods. Also, morphological studies will be performed on dog hearts with induced hypertrophy. The major objectives of the studies on salamanders are: (1) to elucidate the sequence of events and mechanisms of myofibrillogenesis and; (2) to determine how inductive interactions operate to regulate heart differentiation. In the cardiomyopathic hamster system we hope to determine: (1) what the state of myofibrils and their constituent proteins are at various stages of the disease; (2) why there is a disorganization of myofibrils in hypertrophied hearts; (3) what relationship this myofibril disorganization has to the onset of hypertrophy. By understanding these relationships in this unique genetic animal model of cardiac hypertrophy, it is thought that direct correlations can be made with the development and onset of heart hypertropny in humans. The special problems associated with both mutations may provide a key for understanding how trophic interactions control myoblast differentiation. In a broader sense these "birth defects" are potentially capable of helping to answer one of the major unsolved problems in modern biology: the control of gene expression in animals.