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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL059875-03
Application #
6184107
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Wang, Lan-Hsiang
Project Start
1998-08-01
Project End
2002-03-31
Budget Start
2000-08-01
Budget End
2002-03-31
Support Year
3
Fiscal Year
2000
Total Cost
$237,372
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109