Original Paper

Involvement of c-Jun-JNK Pathways in the Regulation of Programmed Cell Death of Developing Chick Embryo Spinal Cord Motoneurons
Joan Ribera, Victoria Ayala, Celia Casas

Universitat de Lleida, Facultat de Medicina, Departament de Ciències Mèdiques Bàsiques, Lleida, Spain

Address of Corresponding Author

Dev Neurosci 2007;29:438-451 (DOI: 10.1159/000097318)

  Key Words

• c-Jun phosphorylation
• Programmed cell death
• Apoptosis
• Motoneuron
• Chick embryo

  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 -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 -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.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Joan Ribera
Universitat de Lleida, Departament de Ciències Mèdiques Bàsiques
Montserrat Roig, 2
ES-25008 Lleida (Spain)
Tel. +34 973 702 415, Fax +34 973 702 426, E-Mail joan.ribera@cmb.udl.es

  Article Information

Received: June 6, 2006
Accepted after revision: August 3, 2006
Published online: November 20, 2006
Number of Print Pages : 14
Number of Figures : 6, Number of Tables : 0, Number of References : 61