Brn-3a activates the expression of Bcl-x(L) and promotes neuronal survival in vivo as well as in vitro
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-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.
460-470
Smith, Martin D.
871dbd2f-83bb-4c7e-ab1d-c890394db215
Melton, Lisa A.
d4edc19f-ffa4-4c26-a4bd-17c4d8581e35
Ensor, Elizabeth A.
534c139f-f4ca-4420-ab64-6bd80e955e63
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Anderson, Patrick
83a36a74-b80d-4be7-8fa4-bad05ccd3e1b
Kinloch, Ross A.
a8dbafbd-449c-4737-8f21-2397b1141937
Latchman, David S.
71e9db7c-9075-4b49-afac-6413085378db
2001
Smith, Martin D.
871dbd2f-83bb-4c7e-ab1d-c890394db215
Melton, Lisa A.
d4edc19f-ffa4-4c26-a4bd-17c4d8581e35
Ensor, Elizabeth A.
534c139f-f4ca-4420-ab64-6bd80e955e63
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Anderson, Patrick
83a36a74-b80d-4be7-8fa4-bad05ccd3e1b
Kinloch, Ross A.
a8dbafbd-449c-4737-8f21-2397b1141937
Latchman, David S.
71e9db7c-9075-4b49-afac-6413085378db
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), .
(doi:10.1006/mcne.2000.0927).
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
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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: 16 Mar 2024 03:14
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Author:
Martin D. Smith
Author:
Lisa A. Melton
Author:
Elizabeth A. Ensor
Author:
Patrick Anderson
Author:
Ross A. Kinloch
Author:
David S. Latchman
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