Download Phosphorylation of c-Jun in avian and mammalian motoneurons in

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, PhD
Department of Anatomy, Korea University College of Medicine
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 cJun-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.