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Brn-3a activates the expression of Bcl-x(L) and promotes neuronal survival in vivo as well as in vitro

Smith, Martin D., Melton, Lisa A., Ensor, Elizabeth A., Packham, Graham, Anderson, Patrick, Kinloch, Ross A. and Latchman, David S. (2001) Brn-3a activates the expression of Bcl-x(L) and promotes neuronal survival in vivo as well as in vitro Molecular and Cellular Neuroscience, 17, (3), pp. 460-470. (doi:10.1006/mcne.2000.0927).

Record type: Article

Abstract

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-xL, 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-xL 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-xL 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.

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Published date: 2001

Identifiers

Local EPrints ID: 26609
URI: http://eprints.soton.ac.uk/id/eprint/26609
ISSN: 1044-7431
PURE UUID: 3a8c392a-6d2c-4b1a-a0c3-e32b729a821c

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Date deposited: 24 Apr 2006
Last modified: 17 Jul 2017 16:06

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Contributors

Author: Martin D. Smith
Author: Lisa A. Melton
Author: Elizabeth A. Ensor
Author: Graham Packham
Author: Patrick Anderson
Author: Ross A. Kinloch
Author: David S. Latchman

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