Bcl-2 is required for cranial sensory neuron survival at defined stages of embryonic development.
To ascertain the role of endogenous Bcl-2 in maintaining the survival of developing neurons and modulating their responses to neurotrophins, we compared the in vitro and in vivo survival of cranial sensory neurons of wild-type and bcl-2 null mouse embryos. At the peak of naturally occurring neuronal death in the trigeminal ganglion at E14, trigeminal neurons from bcl-2(-/-) embryos initially survived in culture in response to NGF but were not sustained as well as neurons from wild-type embryos. At the end of the period of naturally occurring neuronal death at E18, Bcl-2-deficient trigeminal neurons survived with NGF as well as wild-type neurons. At E14 in vivo, the number of trigeminal neurons undergoing apoptosis was significantly greater in bcl-2(-/-) embryos, and there were significantly fewer neurons in the trigeminal ganglia of bcl-2(-/-) embryos at E16 and E18. Similar age-related changes in the responses of nodose ganglion neurons to BDNF were observed in cultures established from bcl-2(-/-) and wild-type embryos between E14 and E18. These results suggest that endogenous Bcl-2 is required for the sustained survival response of a subset of cranial sensory neurons to neurotrophins at particular stages of embryonic development and show that its absence leads to reduced numbers of these neurons in vivo.
Piñón
L G
LG
School of Biological and Medical Sciences, University of St Andrews, Fife, UK.
Middleton
G
G
Davies
A M
AM
D000818:Animals; D016923:Cell Death / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009420:Nervous System / Q000166:cytology* / Q000196:embryology*; D009475:Neurons, Afferent / Q000166:cytology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*
D019253:Proto-Oncogene Proteins c-bcl-2