How spatial specificity of cellular identities is generated is a central question of organogenesis. The heart in Drosophila is a simple and well-defined organ that consists of only a few cell types. Nevertheless, its embryonic origin and initial tubular structure is reminiscent of the early events of vertebrate heart development. We (and others) have characterized: the role of tinman, a mesoderm-endogenous transcription factor, which acts in combination with the ectodermal patterning signals encoded by dpp (bmp-type TGF-beta) and wingless (Wnt) in directing mesodermal progenitors to assume a cardiac fate in discrete dorsal positions. Vertebrate relatives of these factors also have early cardiogenic functions, strongly supporting the idea that basic molecular-genetic mechanisms, of precardiac mesoderm formation are conserved. In this proposal, we would like to continue in taking advantage of the Drosophila model, and propose to elucidate the genetic basis of cellular diversification and cell-type-specific transcription among the heart progenitors and their descendants. We are interested in understanding the molecular-genetic mechanisms by which particular cell-types are selected and confined to a precise location, and what the role of each cell-type is during cardiac organ formation and function. To achieve this goal we plan to concentrate our efforts primarily on the even-skipped (eve) expressing lineage 'of the cardiac mesoderm, since its genetic determination and the transcriptional control of eve is best understood among these cardiac lineages (see Progress Report and Preliminary Data; Su et al., 1999a, in Appendix; Fujioka et al., 1999). Specifically, we plan to study (in Aim 1) the specification and distinction of the Eve lineage and other cardiac cell fates along the anterior posterior axis of the linear heart tube by inductive signals and mesodermal context factors (as well as Notch), to dissect (in Aim 2) the combinatorial transcriptional mechanisms by which eve expression is activated in a spatially well-defined subset of heart cells and, and to screen (in Aim 3) for new genes that are involved in regulating eve expression as well as genes that might be mediating its role in cardiac function.
These aims are designed to further exploit the versatile Drosophila model of heart development and to continue to gain pioneering insights into general cardiogenic principles that will be instrumental in understanding the development and function of the vertebrate heart.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cell Development and Function Integrated Review Group (CDF)
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Pearson, Gail D
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University of Michigan Ann Arbor
Schools of Arts and Sciences
Ann Arbor
United States
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