Drosophila melanogaster has been acknowledged as a premier genetic model system for understanding gene function, developmental networks and molecular basis for genetic disorders including cancers. Drosophila has blood cells or hemocytes that are important for innate immune functions as well as tissue remodeling and wound healing. We initiated a molecular genetic analysis of Drosophila hematopoiesis with the goal to understand the relationship of this process to vertebrate blood development and disorders such as Leukemia. We found that a gene sharing similarity to the Acute Myeloid Leukemia (AML1) protein is essential for the development of 1 of the hemocyte types in Drosophila, called crystal cells. This work led to a lineage diagram for Drosophila hematopoiesis that showed several conserved components. Also the strategies for this development are conserved with similar signaling pathways involved in Drosophila and vertebrate hematopoiesis. More remarkably, concepts such as a common precursor for vascular and blood cells (hemangioblasts) are also conserved. In this proposal, we will first further analyze the functions of the conserved Notch/ PDGF-VEGF receptor/JAK-STAT pathways in Drosophila hematopoieis. We will develop microscopic imaging methods to analyze the hematopoietic process at a single cell level. We will find the molecular basis for the asymmetry that allows hemangioblast divisions to create mixed cell types. And finally, we will analyze novel genes identified from a genetic screen and initiate new genetic screens to identify precursor and possibly stem cell populations and novel proteins that are involved in Drosophila and vertebrate blood cell maturation.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Development - 1 Study Section (DEV)
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Di Fronzo, Nancy L
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University of California Los Angeles
Schools of Arts and Sciences
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United States
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Cho, Bumsik; Spratford, Carrie M; Yoon, Sunggyu et al. (2018) Systemic control of immune cell development by integrated carbon dioxide and hypoxia chemosensation in Drosophila. Nat Commun 9:2679
Mondal, Bama Charan; Shim, Jiwon; Evans, Cory J et al. (2014) Pvr expression regulators in equilibrium signal control and maintenance of Drosophila blood progenitors. Elife 3:e03626
Evans, Cory J; Liu, Ting; Banerjee, Utpal (2014) Drosophila hematopoiesis: Markers and methods for molecular genetic analysis. Methods 68:242-51
Grigorian, Melina; Liu, Ting; Banerjee, Utpal et al. (2013) The proteoglycan Trol controls the architecture of the extracellular matrix and balances proliferation and differentiation of blood progenitors in the Drosophila lymph gland. Dev Biol 384:301-12
Shim, Jiwon; Mukherjee, Tina; Mondal, Bama Charan et al. (2013) Olfactory control of blood progenitor maintenance. Cell 155:1141-53
Honti, Viktor; Cinege, Gyöngyi; Csordás, Gábor et al. (2013) Variation of NimC1 expression in Drosophila stocks and transgenic strains. Fly (Austin) 7:263-6
Shim, Jiwon; Mukherjee, Tina; Banerjee, Utpal (2012) Direct sensing of systemic and nutritional signals by haematopoietic progenitors in Drosophila. Nat Cell Biol 14:394-400
Mondal, Bama Charan; Mukherjee, Tina; Mandal, Lolitika et al. (2011) Interaction between differentiating cell- and niche-derived signals in hematopoietic progenitor maintenance. Cell 147:1589-600
Mukherjee, Tina; Kim, William Sang; Mandal, Lolitika et al. (2011) Interaction between Notch and Hif-alpha in development and survival of Drosophila blood cells. Science 332:1210-3
Sinenko, Sergey A; Shim, Jiwon; Banerjee, Utpal (2011) Oxidative stress in the haematopoietic niche regulates the cellular immune response in Drosophila. EMBO Rep 13:83-9

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