GENE EXPRESSION IN THE DEVELOPING AND AGING HEART

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In the last few years the cardiovascular system has emerged as one of the most exciting new areas for studying the molecular mechanisms controlling and maintaining organ morphology. The recent fusion of classical embryological approaches with genetic analysis in a variety of organisms has resulted in the discovery of multiple genetic factors guiding the specification of cardiac progenitor cells and the spatiotemporal controls underlying their differentiation. New genetic interfaces between heart myogenesis and morphogenesis have also been revealed. From these recent breakthroughs, it is becoming increasingly clear that many of the congenital pathologies and problems specific to the aging heart can only be understood by tracing their origins in embryonic development. Moreover, it seems clear that for the huge economic investinent in human cardiovascular research to pay off, a thorough understanding of the genetic mechanisms acting in heart development and aging is not only necessary, but a matter of some urgency. The goal of this pilot project is to pool the expertise of our two laboratories to develop an important resource that will facilitate a comprehensive dissection of cardiac organogenesis. We propose to create a catalogue of 10,000 DNA sequences representing genes expressed in the murine embryonic linear heart tube. This catalogue will be developed as an interactive database of heart-expressed genes from which novel sequences can be identified, inter-relationships established, and individual clones rapidly isolated. Once novel or known genes of interest are identified in the screen, their expression patterns will be compared in embrvonic adult and aging heart tissue. The database will constitute a novel and imnortant reagent in the heart field. It can be broadly disseminated and is directly applicable to the rapidly expanding initiative to understand the genetic circuitry underlying heart development and how this circuitry fails in the maladapted, diseased and aging heart.