BAX is required for neuronal death after trophic factor deprivation and during development.
Members of the BCL2-related family of proteins either promote or repress programmed cell death. BAX, a death-promoting member, heterodimerizes with multiple death-repressing molecules, suggesting that it could prove critical to cell death. We tested whether Bax is required for neuronal death by trophic factor deprivation and during development. Neonatal sympathetic neurons and facial motor neurons from Bax-deficient mice survived nerve growth factor deprivation and disconnection from their targets by axotomy, respectively. These salvaged neurons displayed remarkable soma atrophy and reduced elaboration of neurities; yet they responded to readdition of trophic factor with soma hypertrophy and enhanced neurite outgrowth. Bax-deficient superior cervical ganglia and facial nuclei possessed increased numbers of neurons. Our observations demonstrate that trophic factor deprivation-induced death of sympathetic and motor neurons depends on Bax.
Deckwerth
T L
TL
Department of Molecular Biology and Pharmacology, Howard Hughes Medical Institute Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Elliott
J L
JL
Knudson
C M
CM
Johnson
E M
EM
Snider
W D
WD
Korsmeyer
S J
SJ
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D019070:Cell Lineage / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D005154:Facial Nerve / Q000166:cytology / Q000601:surgery; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006965:Hyperplasia / Q000235:genetics; D017403:In Situ Hybridization; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010053:Ovary / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000166:cytology; D013737:Testis / Q000473:pathology*; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein