title: Mitosis in neurons: Roughex and APC/C maintain cell cycle exit to prevent cytokinetic and axonal defects in Drosophila photoreceptor neurons.
abstract: The mechanisms of cell cycle exit by neurons remain poorly understood. Through genetic and developmental analysis of Drosophila eye development, we found that the cyclin-dependent kinase-inhibitor Roughex maintains G1 cell cycle exit during differentiation of the R8 class of photoreceptor neurons. The roughex mutant neurons re-enter the mitotic cell cycle and progress without executing cytokinesis, unlike non-neuronal cells in the roughex mutant that perform complete cell divisions. After mitosis, the binucleated R8 neurons usually transport one daughter nucleus away from the cell body into the developing axon towards the brain in a kinesin-dependent manner resembling anterograde axonal trafficking. Similar cell cycle and photoreceptor neuron defects occurred in mutants for components of the Anaphase Promoting Complex/Cyclosome. These findings indicate a neuron-specific defect in cytokinesis and demonstrate a critical role for mitotic cyclin downregulation both to maintain cell cycle exit during neuronal differentiation and to prevent axonal defects following failed cytokinesis.
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Ruggiero
authors.forename: Abhijit
authors.initials: A
authors.lastname: Kale
authors.forename: Barbara
authors.initials: B
authors.lastname: Thomas
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Baker
mesh_terms: D000818:Animals; D064189:Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation; D002455:Cell Division; D004330:Drosophila / Q000235:genetics / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism; D005123:Eye / Q000254:growth & development / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D016547:Kinesins / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000378:metabolism
chemical_list: D064189:Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome; D029721:Drosophila Proteins; D005136:Eye Proteins; C577334:Shtd protein, Drosophila; C088084:rux protein, Drosophila; D004398:Dyneins; D016547:Kinesins