Signal transduction and transcriptional adaptation in embryonic heart development and during myocardial hypertrophy

In comparing the pathological state of cardiac hypertrophy with early embry onic growth and development of the primitive heart, important and informati ve aspects of mechanisms that underlie activation of the gene expression pa ttern become apparent. Interestingly, in both cases the muscle phenotypes s hare the expression of a 'fetal' gene expression program, raising the quest ion whether the same genetic mechanism is being called upon by signals asso ciated with the onsets of cardiogenesis and myocardial hypertrophy. A cell specific transcription factor, CLP-1, was recently identified in our labora tory that is likely to play a crucial role, in conjunction with other known regulatory factors, in early cardiac events leading to cardiogenic cell sp ecification and differentiation. We have also identified a novel mechanism that involves activation of the Jak/Stat signaling pathway that is linked t o the autocrine angiotensin-II loop associated with the hypertrophic respon se in cardiomyocytes. Since early cardiac cell development and the hypertro phic state involve the expression of the same battery of genes, one may spe culate that common transcription factors may account for assembling a compe tent apparatus responsible for transcribing the genes. Our present studies are designed to investigate the potential role of these factors in control of both processes.