Differences in bcl-2- and bax-independent function in regulating apoptosis in sensory neuron populations.
Bcl-2 and Bax are cytoplasmic proteins that have antagonistic actions on apoptosis. To investigate the extent to which these proteins function independently in regulating neuronal apoptosis, we studied the in vivo and in vitro development of two populations of sensory neurons of mouse embryos that lack one or both proteins. Absence of Bcl-2 increased neuronal apoptosis and reduced the number of neurons in both the trigeminal and nodose ganglia during the period of naturally occurring neuronal death. Absence of Bax reduced neuronal apoptosis and increased the number of surviving neurons in these ganglia and promoted sustained neuronal survival in neurotrophin-free cultures. In contrast, the elimination of both Bcl-2 and Bax had different consequences for these populations of neurons. In nodose ganglia, apoptosis was suppressed just as effectively in embryos lacking both proteins as in embryos lacking Bax alone, and neurons that lacked both proteins survived just as effectively in neurotrophin-free medium as Bax-deficient neurons. This suggests that for nodose neurons, the suppression of apoptosis by Bcl-2 is entirely dependent on the presence of Bax. In trigeminal ganglia, although neuronal apoptosis was reduced in embryos lacking both proteins compared with wild-type embryos, there were significantly more apoptotic neurons and significantly fewer surviving neurons in embryos lacking both proteins compared with Bax-deficient embryos, and significantly fewer trigeminal neurons from embryos lacking both proteins survived in neurotrophin-free medium compared with trigeminal neurons that lacked Bax alone. This suggests that for trigeminal neurons, Bcl-2 functions partly independently of Bax in regulating survival. Our results therefore suggest that the relative independence of Bcl-2 and Bax in regulating neuronal survival differs from one population of neurons to another.
Middleton
G
G
School of Biomedical Sciences, Biomedical Building, University of St. Andrews, St. Andrews, Fife KY16 9AJ, Scotland.
Cox
S W
SW
Korsmeyer
S
S
Davies
A M
AM
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D019940:Genes, bcl-1 / Q000235:genetics; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D009620:Nodose Ganglion / Q000166:cytology / Q000196:embryology / Q000502:physiology; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000196:embryology / Q000502:physiology; D014404:Tubulin / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014404:Tubulin; D051028:bcl-2-Associated X Protein