Genetic Dissection of Drosophila Hematopoiesis

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DESCRIPTION (Applicant's abstract): The study of lineage specification during hematopoiesis in mammals is important due to its relationship to many blood related disorders including Leukemia. However, many fundamental questions regarding the specification of unique fates remain unresolved. Drosophila has a simple hematopoietic system constituting of cell types that function in innate immunity and phagocytosis. A hierarchy of multiple transcription factors that specify hematopoietic lineage in Drosophila have been identified. The GATA factor Serpent is required for all hematopoiesis. Lozenge, which bears similarity to the Acute Myeloid Leukemia protein in humans is required for the development of one blood cell type, the crystal cells in Drosophila. Gcm is required for the development of the plasmatocytes/macrophages. Recently we have established that the Notch receptor and its ligand Serrate are involved in the induction of blood cells in Drosophila. In this proposal, we present a comprehensive analysis of Drosophila hematopoiesis. The role of Serpent in larval hematopoiesis will be studied; the involvement of the Notch pathway in blood cell development will be fully analyzed. The hematopoietic precursor population will be characterized. A comprehensive genetic study will be performed for a possible role of the many known signal transduction cascades in the process of hematopoieis. Finally, genetic screens will identify genes that are involved in Drosophila hematopoiesis. Given the similarity of the known members of this developmental system with proteins with important function in mammalian hematopoiesis, we expect that many of the new genes identified will have relevance to this important developmental process in mammals.