Phosphorylation of c-Jun in avian and mammalian motoneurons in vivo during programmed cell death

An early reversible event in the apoptotic cascade

Woong Sun, Thomas W. Gould, Jason Newbern, Carol Milligan, So Yoen Choi, Hyun Kim, Ronald W. Oppenheim

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

c-Jun is a transcription factor that is involved in various cellular events, including apoptotic cell death. For example, phosphorylation of c-Jun is one of the earliest biochemical changes detected in dying sympathetic neurons after NGF deprivation in vitro. However, currently, it is not known whether a similar molecular event is involved in the developmental programmed cell death (PCD) of neurons in vivo. We observed that only a subpopulation of motoneurons (MNs) exhibit c-Jun phosphorylation during the PCD period in chick [embryonic day 5 (E5)-E12] and mouse (E13-E18) embryos. Experimental perturbation of MN survival-promoting signals by limb bud removal (reduced signals) or by activity blockade (increased signals) in the chick embryo demonstrated that the presence of those signals is negatively correlated with the number of c-Jun-phosphorylated MNs. This suggests that insufficient survival signals (e.g., neurotrophic factors) may induce c-Jun phosphorylation of MNs in vivo. Consistent with the idea that c-Jun phosphorylation is a reversible event during normal PCD of MNs, we found that c-Jun phosphorylation was transiently observed in a subpopulation of mouse MNs rescued from PCD by deletion of the proapoptotic gene Bax. Inhibition of c-Jun signaling significantly reduced MN death in chick embryo, indicating that activation of c-Jun signaling is necessary for the PCD of MNs. Together, c-Jun phosphorylation appears to be required for the initiation of an early and reversible event in the intracellular PCD cascade in vivo after loss of survival-promoting signals such as neurotrophic factors.

Original languageEnglish
Pages (from-to)5595-5603
Number of pages9
JournalJournal of Neuroscience
Volume25
Issue number23
DOIs
Publication statusPublished - 2005 Jun 8

Fingerprint

Motor Neurons
Cell Death
Phosphorylation
Nerve Growth Factors
Chick Embryo
Limb Buds
Neurons
Gene Deletion
Nerve Growth Factor
Transcription Factors
Embryonic Structures

Keywords

  • c-Jun
  • Cell death
  • In vivo
  • Motoneurons
  • Phosphorylation
  • Target

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Phosphorylation of c-Jun in avian and mammalian motoneurons in vivo during programmed cell death : An early reversible event in the apoptotic cascade. / Sun, Woong; Gould, Thomas W.; Newbern, Jason; Milligan, Carol; Yoen Choi, So; Kim, Hyun; Oppenheim, Ronald W.

In: Journal of Neuroscience, Vol. 25, No. 23, 08.06.2005, p. 5595-5603.

Research output: Contribution to journalArticle

Sun, Woong ; Gould, Thomas W. ; Newbern, Jason ; Milligan, Carol ; Yoen Choi, So ; Kim, Hyun ; Oppenheim, Ronald W. / Phosphorylation of c-Jun in avian and mammalian motoneurons in vivo during programmed cell death : An early reversible event in the apoptotic cascade. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 23. pp. 5595-5603.
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