Hemocytes or blood cells play an important role in the cellular immune response of Drosophila and are involved in the phagocytosis of pathogenic microbes and in the encapsulation of larger foreign invaders. Recent studies have highlighted striking similarities between innate immunity in vertebrates and the immune response of insects. The precise mechanism by which distinct types of blood cells are generated in Drosophila is still poorly understood. Our preliminary experiments show that Notch may play a crucial role in cell-fate determination during hematopoiesis. A goal of this proposal is to study the specific function of Notch in blood cell development by using mutant forms of Notch and to test if the Notch and Jak-Stat pathways interact to regulate hematopoiesis in Drosophila. In addition, we propose to conduct a genetic screen to identify genes that play an important role in regulating the proliferation of blood cell precursors and in specifying distinct hematopoietic fates. We anticipate that these studies will provide insights into the genetic pathways that regulate both Drosophila and mammalian hematopoiesis.