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 language | English |
|---|---|
| Pages (from-to) | 5595-5603 |
| Number of pages | 9 |
| Journal | Journal of Neuroscience |
| Volume | 25 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - 2005 Jun 8 |
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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 journal › Article
}
TY - JOUR
T1 - Phosphorylation of c-Jun in avian and mammalian motoneurons in vivo during programmed cell death
T2 - An early reversible event in the apoptotic cascade
AU - Sun, Woong
AU - Gould, Thomas W.
AU - Newbern, Jason
AU - Milligan, Carol
AU - Yoen Choi, So
AU - Kim, Hyun
AU - Oppenheim, Ronald W.
PY - 2005/6/8
Y1 - 2005/6/8
N2 - 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.
AB - 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.
KW - c-Jun
KW - Cell death
KW - In vivo
KW - Motoneurons
KW - Phosphorylation
KW - Target
UR - http://www.scopus.com/inward/record.url?scp=20444400796&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20444400796&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4970-04.2005
DO - 10.1523/JNEUROSCI.4970-04.2005
M3 - Article
VL - 25
SP - 5595
EP - 5603
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 23
ER -