The long-term goal of this application is to use the Drosophila system to define basic molecular mechanisms in heart development. Drosophila have a primitive cardiac tube termed the dorsal vessel which comprises a number of unique cell types, each of which perform specific functions in the mature organ. While much is known concerning how the heart cells are initially specified there is still much to learn concerning how individual cells in the cardiac mesoderm acquire unique fates. We shall use genetics and molecular biology to identify transcriptional regulators of genes with restricted patterns of expression in the dorsal vessel, and to understand how unique cells types arise and differentiate from within the cardiac mesoderm. There is now convincing evidence that the molecular mechanisms of cardiac specification and differentiation are strongly conserved through evolution, and we believe that this will also prove to be the case for the acquisition of unique cell types with the cardiac lineage, as proposed here. Therefore our research will have direct relevance to the understanding of vertebrate heart development including in humans. Furthermore, since a number of congenital heart defects have recently been shown to arise from mutation of cardiac transcription factors, our studies regarding the transcriptional control of heart cell fate are likely to provide critical basic information for understanding the mechanisms of cardiac disease in vertebrates.
