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J. Biol. Chem., Vol. 276, Issue 7, 5204-5212, February 16, 2001
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From the Medical Molecular Biology Unit, Institute of Child Health,
University College London, 30 Guilford Street,
London WC1N 1EH, United Kingdom
Inactivation of the gene encoding the POU domain
transcription factor BRN-3A results in the absence of specific neurons
in knockout mice. Here we demonstrate for the first time a direct effect of BRN-3A on the survival of neuronal cells. Specifically, overexpression of BRN-3A in cultured trigeminal ganglion or dorsal root
ganglion sensory neurons enhanced their survival following the
withdrawal of nerve growth factor. Moreover, reduction of BRN-3A levels
impaired the survival of these neurons. The survival of sympathetic
neurons was not affected by either approach. Similarly, overexpression
of BRN-3A activated the endogenous Bcl-2 gene in trigeminal
neurons, but not in sympathetic neurons. The protective effect of
BRN-3A on trigeminal neuron survival following nerve growth factor
withdrawal significantly increased during embryonic development. In
contrast, overexpression of the related factor BRN-3B enhanced survival
of trigeminal neurons only at an early stage of embryonic development.
Thus, BRN-3A (and in some circumstances, BRN-3B) can promote the
survival of nerve growth factor-dependent sensory but not
sympathetic neurons, allowing it to play a direct role in the survival
of some (but not all) neuronal populations in the developing and adult
nervous systems.
The BRN-3A Transcription Factor Protects Sensory but Not
Sympathetic Neurons from Programmed Cell Death/Apoptosis*
*
This work was supported by Action Research, the Medical
Research Council, and the Sir Jules Thorn Charitable Trust.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 44-20-7829-8693;
Fax: 44-20-7242-8437; E-mail: d.latchman@ich.ucl.ac.uk.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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