title: Involvement of c-Jun-JNK pathways in the regulation of programmed cell death of developing chick embryo spinal cord motoneurons.
abstract: Key features of developmentally regulated programmed cell death (PCD) have been described for the first time in the chick nervous system. JNK/c-Jun pathway was involved in early events determining normal and pathological neuronal death as shown in experimental models. In the chick embryo, PCD of motoneurons (MNs) in ovo occurs within a well-defined temporal window and can be subjected to experimental manipulation. Taking advantage of this in vivo system, we explored the role of c-Jun and JNK pathway in the regulation of PCD in MNs. By using specific antibodies against phospho-c-Jun (Ser 63, 73) and JNK we demonstrated that before MNs acquire apoptotic phenotype there is an increase in c-Jun. Blockage of neuromuscular activity by the GABA agonist muscimol reduces PCD and diminishes c-Jun immunoreactivity in MNs. Extensive induction of PCD, either due to injection of beta-bungarotoxin or limb bud removal, is also preceded by an increase in c-Jun immunoreactivity that is also associated with upregulation of phospho-c-Jun and JNK. Translocation of JNK from cytoplasm to MN nuclei was also detected. After acute application of beta-bungarotoxin, which is a strong apoptotic stimulus for MNs, c-Jun phosphorylation occurs on serine 73, whereas serine 63 is the main site for c-Jun phosphorylation after limb bud removal. These results demonstrated that the JNK/c-Jun pathway is involved in the decision phase of normal and induced apoptosis in MNs. Pharmacological interventions involving this pathway should be explored as a potential therapeutic target for promoting MN survival.
authors.affiliation: Universitat de Lleida, Facultat de Medicina, Departament de Ciències Mèdiques Bàsiques, Lleida, Spain. joan.ribera@cmb.udl.es
authors.forename: Joan
authors.initials: J
authors.lastname: Ribera
authors.forename: Victoria
authors.initials: V
authors.lastname: Ayala
authors.forename: Celia
authors.initials: C
authors.lastname: Casas
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001692:Biological Transport; D002038:Bungarotoxins / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002642:Chick Embryo / Q000166:cytology / Q000502:physiology*; D005121:Extremities / Q000196:embryology; D018755:GABA Agonists / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013116:Spinal Cord / Q000196:embryology*
chemical_list: D002038:Bungarotoxins; D018755:GABA Agonists; D016755:Proto-Oncogene Proteins c-jun; D009118:Muscimol; D048031:JNK Mitogen-Activated Protein Kinases