I also pursue a similar theme in gene regulation using Drosophila hematopoiesis as model. Unlike hedgehog signaling, there is little known about blood cell development in Drosophila. Thus, this project involves more descriptive aspects than the shanti and oroshigane project.
Hemocytes from a wild type larva. They are small and round. Stained with Giemsa stain. Hemocytes from semushi mutant larva. They are varied in shape and in size. The accumulation of larger blood cells is similar to those of human leukemia. Stained with Giemsa stain.
Contrasted to the systems in mammals, Drosophila only has the innate immune system, which consists of antimicrobial agent synthesis and of macrophage production. Production of these cells likely parallels the monocyte/macrophage lineage in mammals. Interestingly, in both Drosophila and mammals, the pathway involving NF-kB (Drosophila has NF-kB homologues, dosal, DIF, and Relish) functions to produce these immune cells. I am working on an enzyme (encoded by the semushi gene) that modifies inhibitors of NF-kB, IkB. Semushi and its homologues activate IkBs by adding small ubiquitin-like modifiers (SUMO). Thus, loss-of-function mutations of these enzymes keep IkBs inactive. This in turn maintains NF-kB activity at a higher level, which results in a drastic increase in blood cell count in Drosophila. Such mutant animals die at the end of larval development. The study of Drosophila hematopoiesis is less understood compared to other areas. I hope that our mutations allow us to take a genetic approach with which I can identify genes required for blood cell development. At the same time, I can investigate how other known genes interact with each other to make the blood cell precursors and to make them differentiate into mature immune cells. In the future, I hope to help leukemia patients by providing other researches with fundamental knowledge obtained in my laboratory.
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