title: JNK pathway activation is able to synchronize neuronal death and glial phagocytosis in Drosophila.
abstract: Glial phagocytosis of superfluous neurons and damaged or aberrant neuronal material is crucial for normal development and maintenance of the CNS. However, the molecular mechanisms underlying the relationship between neuronal death and glial phagocytosis are poorly understood. We describe a novel mechanism that is able to synchronize neuronal cell death and glial phagocytosis of dying neurons in the Drosophila embryonic CNS. This mechanism involves c-Jun N-terminal kinase (JNK) signaling, which is required for developmental apoptosis of specific neurons during embryogenesis. We demonstrate that the dJNK pathway gain-of-function in neurons leads to dJNK signaling in glia, which results in upregulation of glial phagocytosis. Importantly, this promotion of phagocytosis is not mediated by upregulation of the glial phagocytic receptors SIMU and DRPR, but by increasing glial capacity to degrade apoptotic particles inside phagosomes. The proposed mechanism may be important for removal of damaged neurons in the developing and mature CNS.
authors.affiliation: Department of Genetics and Developmental Biology, Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Haifa 31096, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Shklover
authors.affiliation: Department of Genetics and Developmental Biology, Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Haifa 31096, Israel.
authors.forename: K
authors.initials: K
authors.lastname: Mishnaevski
authors.affiliation: Department of Genetics and Developmental Biology, Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Haifa 31096, Israel.
authors.forename: F
authors.initials: F
authors.lastname: Levy-Adam
authors.affiliation: Department of Genetics and Developmental Biology, Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Haifa 31096, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Kurant
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010587:Phagocytosis / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D048031:JNK Mitogen-Activated Protein Kinases