The identification and characterization of novel genes and pathways involved in Drosophila melanogaster hematopoiesis

Parallels between vertebrate and Drosophila hematopoiesis add to the value of flies as a model organism to gain insights into blood development. These parallels include lineage hierarchy, multiple waves and shifting sites of hematopoiesis, functionality, signaling factors, and disease. The Drosophila hematopoietic system is composed of three classes of terminally differentiated blood cells: plasmatocytes, crystal cells, and lamellocytes. Recent studies have suggested a lineage pathway in Drosophila involving proteins similar to those seen in human blood development. To identify additional genes involved in Drosophila hematopoiesis we have conducted a P-element screen to isolate mutations that affect embryonic crystal cell development. Using a marker of terminally differentiated crystal cells, we screened 1040 P-element lethal lines covering approximately 25% of the Drosophila genome. We identified 42 individual lines that cause a reduction in crystal cell number and two lines that result in crystal cell mislocalization. Identifying novel genes and pathways involved in Drosophila hematopoiesis may provide further insight into mammalian hematopoiesis and leukemia.;Our studies of Drosophila hematopoiesis indicate that the upregulation of labial by gap-like genes during the blastoderm stage of development, independent of Dpp signaling, is most likely involved in the specification of the crystal cell primordia. We show that Dpp plays a non-cell autonomous and most likely, an indirect role in the promotion both lineages of blood cell development genetically downstream of Srp expression. This work has also identified a role for EGFR and ebi in Drosophila hematopoiesis. These studies indicate that EGFR may be acting through ebi to regulate crystal cell development and working independently of ebi to regulate the proliferation and migration of plasmatoctyes.