Tumor suppressor gene OSCP1/NOR1 regulates apoptosis, proliferation, differentiation, and ROS generation during eye development of Drosophila melanogaster.
OSCP1/NOR1 (organic solute carrier partner 1/oxidored nitrodomain-containing protein 1) is a known tumor suppressor protein. OSCP1 has been reported to mediate transport of various organic solutes into cells; however, its role during development has not yet been addressed. Here we report the results of studies on dOSCP1 (the Drosophila ortholog of hOSCP1) to elucidate the role of OSCP1/NOR1 during development. Knockdown of dOSCP1 in the eye imaginal discs induced a rough-eye phenotype in adult flies. This phenotype resulted from induction of caspase-dependent apoptosis followed by a compensatory cell proliferation and generation of reactive oxygen species in eye imaginal discs. The induction of apoptosis appears to be associated with down-regulation of the anti-apoptotic Buffy gene and up-regulation of the pro-apoptotic Debcl gene. These effects of knockdown of dOSCP1 lead to mitochondrial fragmentation, degradation, and a shortfall in ATP production. We also found that knockdown of dOSCP1 causes a defect in cone cell and pigment cell differentiation in pupal retinae. Moreover, mutations in epidermal growth factor receptor pathway-related genes, such as Spitz and Drk, enhanced the rough-eye phenotype induced by dOSCP1 knockdown. These results suggest that dOSCP1 positively regulates the epidermal growth factor receptor signaling pathway. Overall, our findings indicate that dOSCP1 plays multiple roles during eye development in Drosophila.
['Huu|Nguyen Tho|NT|', 'Yoshida|Hideki|H|', 'Yamaguchi|Masamitsu|M|']
D000818:Animals D030801:Animals, Genetically Modified D017209:Apoptosis D002454:Cell Differentiation D049109:Cell Proliferation D003433:Crosses, Genetic D029721:Drosophila Proteins D004331:Drosophila melanogaster D066246:ErbB Receptors D005123:Eye D018507:Gene Expression Regulation, Developmental D055785:Gene Knockdown Techniques D060227:Imaginal Discs D007814:Larva D026901:Membrane Transport Proteins D008855:Microscopy, Electron, Scanning D009154:Mutation D017956:Photoreceptor Cells, Invertebrate D034622:RNA Interference D017382:Reactive Oxygen Species D018010:Receptors, Invertebrate Peptide D015398:Signal Transduction
OSCP1/NOR1 apoptosis proliferation differentiation ROS Drosophila cone cell pigment cell EGFR pathway compound eye development