title: Limited role of developmental programmed cell death pathways in Drosophila norpA retinal degeneration.
abstract: We examined the role of programmed cell death (PCD) pathways in retinal degeneration caused by a mutation in the norpA gene. norpA degeneration shows morphological hallmarks of programmed cell death, specifically cytoplasmic condensation and engulfment of the dying photoreceptor cells by neighboring retinal pigment cells. However, genetic mosaic analysis of adult photoreceptors lacking rpr, hid, and grim show that these PCD inducers are not required for norpA degeneration. We showed previously that ectopic expression of either rpr or hid triggers rapid PCD in adult photoreceptors, and this is completely suppressed by the coexpression of the baculoviral P35 caspase inhibitor. In contrast, expression of P35 does not suppress norpA retinal degeneration, although a small delay in the rate of degeneration is observed in low light-low temperature conditions. P35 does not alter the morphological characteristics of norpA cell death. Overexpression of the Drosophila inhibitor of apoptosis Diap1 or a dominant-negative form of the Dronc caspase, even when coexpressed with P35, does not dramatically alter the time course of norpA degeneration. These results establish that the pathways responsible for PCD in development do not play a major role in adult retinal degeneration caused by norpA.
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556-0369, USA.
authors.forename: Cheng-Da
authors.initials: CD
authors.lastname: Hsu
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Whaley
authors.forename: Kristin
authors.initials: K
authors.lastname: Frazer
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Miller
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Mitchell
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Adams
authors.forename: Joseph E
authors.initials: JE
authors.lastname: O'Tousa
mesh_terms: D000818:Animals; D017209:Apoptosis; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000235:genetics*; D005123:Eye / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins; D009154:Mutation; D054799:Phospholipase C beta; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000648:ultrastructure; D011401:Promoter Regions, Genetic; D012162:Retinal Degeneration / Q000473:pathology*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000235:genetics*; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D014764:Viral Proteins; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; D010738:Type C Phospholipases; C468371:NorpA protein, Drosophila; D054799:Phospholipase C beta