GENETIC CONTROL OF CARDIAC CELL TYPES AND LINEAGES

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

The genetic basis of the initial determination of the heart mesoderm in Drosophila has been elucidated in considerable detail. Recently, an increasing body of evidence is accumulating that suggests that many molecular and embryological parallels exist between Drosophila and vertebrates in early cardiogenesis. We plan to further exploit the Drosophila model for pioneering the discovery in early cardiogenesis. We plan to further exploit the Drosophila model for pioneering the discovery of new gene systems involved in heart development. Specifically, we propose to study here the cardiogenic role of the growing number of lineage and differentiation genes and define their precise function in specifying individual cardiac cell types in processes subsequent to the initial formation of the cardiac mesoderm. We plan to illuminate the virtually unexplored mechanisms of how individual cell fates with the cardiac mesoderm are specified. Again, many of this new set of potentially cardiogenic genes are conserved in vertebrates suggesting that the Drosophila model of heart development continues to provide pioneering insights into vertebrate cardiogenic principles. The Specific Aims are (1) to determine in detail the cardiac lineages in Drosophila by using a novel genetic method of clonal analysis, (2) to determine the role and interactions of lineage and differentiation genes in distinguishing cardiac cell types, with emphasis on the cytoplasmic factors encoded by numb and sanpodo and the nuclear transcription factors encoded by zfh-1 and evenskipped, (3) to determine if a recently isolated mouse zfh-1 gene is part of a new conserved gene family that plays a role in vertebrate cardiogenesis. In summary, understanding the genetics of the lineages and cell-specific differentiation of the Drosophila heart is expected to greatly facilitate discerning the function of such genes in vertebrate cardiogenesis. We believe that the proposed research will continue to serve as a prototype for studying the genetic basis of heart development, which ultimately will help us fathom the basis of congenital heart disease.