Brn-3a activates the expression of Bcl-x(L) and promotes neuronal survival in vivo as well as in vitro.
The determination of cell fate plays a critical role during the later stages of embryogenesis and the early postnatal period-a time during which approximately half of neurons born during neurogenesis undergo programmed cell death. It has previously been reported that the type IV POU domain transcription factor Brn-3a plays a role in the maturation and survival of sensory neuronal populations. Indeed we have shown that the long form of Brn-3a is capable of activating expression of the antiapoptotic Bcl-2 gene and enhancing neuronal survival in cultures of sensory neurons. In this study, we report the identification of another antiapoptotic family member, Bcl-x(L), as a target gene of Brn-3a in sensory neurons, providing a further mechanism by which Brn-3a determines sensory neuronal fate during development. Bcl-x(L) gene expression is activated by Brn-3a in sensory but not in sympathetic neurons and its expression is reduced by antisense inhibition of Brn-3a expression in sensory neurons. Most importantly, both Bcl-x(L) expression and neuronal survival are enhanced by the overexpression of Brn-3a in dorsal root ganglion in vivo in a model of sciatic nerve injury in the intact animal.
Medical Molecular Biology Unit, Institute of Child Health, University College London, United Kingdom.
M D
MD
Smith
L A
LA
Melton
E A
EA
Ensor
G
G
Packham
P
P
Anderson
R A
RA
Kinloch
D S
DS
Latchman
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D016373:DNA, Antisense; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology; D015870:Gene Expression / Q000502:physiology; D066298:In Vitro Techniques; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology; D017783:Superior Cervical Ganglion / Q000166:cytology; D050818:Transcription Factor Brn-3; D014157:Transcription Factors / Q000235:genetics*; D012668:Trigeminal Ganglion / Q000166:cytology; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D016373:DNA, Antisense; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D050818:Transcription Factor Brn-3; D014157:Transcription Factors; D051020:bcl-X Protein