Similarities exist between heart development in Drosophila and vertebrates, particularly during early stages of organ formation. Cardiogenesis in both systems involves specification of precursor cells within paired progenitor fields, followed by their movement into a linear heart tube structure that eventually morphs into a functional organ. Our long-term objectives are to use the Drosophila model to expediently study and more fully comprehend the genetic bases of heart tube formation, especially as it relates to the analysis of conserved regulatory factors that likely function in human heart development as well. Towards these goals, the expression and function of the Toll transmembrane protein during dorsal vessel formation has been demonstrated. Its regulation by the T-box factor Dorsocross and homeodomain factor Tinman will be further investigated, as well as determining Toll's function as a cell adhesion molecule essential for heart tube formation. During late dorsal vessel morphogenesis, select cardioblasts differentiate into specialized cells that form the valves of the heart tube. A 12-cardioblast enhancer of the wingless gene has been identified that precisely marks these cells. The regulation of this highly-specialized transcriptional control sequence by Dorsocross and the Hox-C factor Abdominal-A will be investigated. Finally, the dorsal vessel expression and function of tailup, the Drosophila homolog of the vertebrate gene encoding the LIM homeodomain factor Isletl, will be analyzed in detail. Together, these investigations will provide extensive new information on the functions of conserved cardiogenic factors in heart tube morphogenesis, with relevance to our understanding of the etiology of certain congenital heart defects observed in humans. Congenital malformations of the heart are the most common birth defects observed in children. An understanding of the genetic bases of these anomalies will require detailed information on the regulatory factors controlling cardiac gene expression and morphogenesis. Developmental and genetic similarities exist between early heart formation in the model organism Drosophila and humans. The determination of the functions and interactions of conserved cardiogenic factors, and the cellular processes they control, will provide needed insights into mechanisms controlling heart development, in both Drosophila and humans.
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