Swiergiel, AH (Dept Pharmacology and Therapeutics, Louisiana State University Medical Center, USA)
Cell division and subsequent programmed cell death in imaginal discs of Drosophila larvae determine the final size of organs and structures of the adult fly. We have found that nitric oxide (NO) acts as an antiproliferative agent and controls cell number during Drosophila development. Drosophila NO synthase (NOS) is coded by a single dNOS gene which generates a family of alternatively spliced transcripts and protein isoforms. NOS gradually accumulates in imaginal discs of Drosophila and reaches maximum levels at the end of the larval development, when DNA synthesis and cell division slow down in most of the cells of imaginal disks and the brain. Inhibition of NOS in larvae results in surplus cell proliferation and excessive growth of the segments of the body of the adult fly. In contrast, ectopic overexpression of the NOS gene causes a decrease in the number of cells and reduction in the size of some segments. The results of BrdU labeling of imaginal disks suggest that modulation of NOS activity directly affects the number, but not the distribution of cells in S phase. The antiproliferative action of NO becomes more evident if the interfering process of programmed cell death is blocked by introducing the p35 gene, a viral inhibitor of apoptosis, in the germline. When we tested the genetic interactions of dNOS with various components of the cell cycle, we found that dNOS interacts with the retinoblastoma pathway to control eye development. Manipulations of dNOS activity can enhance or suppress the effects of the Rbf and dE2F genes on cell cycle progression in Drosophila imaginal discs. Distribution of BrdU-labeled nuclei indicate that NO affects DNA synthesis in eye imaginal disc. Our results argue that NO regulates cell cycle division in developing imaginal discs by controlling entry to the S phase of the cell cycle.
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|Dunn, AJ; Swiergiel, AH; (1998). The Role of Biogenic Amines in Cytokine-induced Hypophagia. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL ../../../|
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