The BRN-3A transcription factor protects sensory but not sympathetic neurons from programmed cell death/apoptosis
The BRN-3A transcription factor protects sensory but not sympathetic neurons from programmed cell death/apoptosis
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DOI：
10.1074/jbc.m007068200
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发表时间：
2001-02-16
影响因子：
4.8
通讯作者：
Latchman, DS
中科院分区：
文献类型：
--
作者：
Ensor, E;Smith, MD;Latchman, DS
编码 POU 结构域转录因子 BRN-3A 的基因失活会导致基因敲除小鼠中特定神经元的缺失。在这里，我们首次证明了 BRN-3A 对神经元细胞存活的直接影响。具体来说，在培养的三叉神经节或背根神经节感觉神经元中过度表达 BRN-3A 可以增强神经生长因子撤除后的存活率。此外，BRN-3A水平的降低损害了这些神经元的存活。交感神经元的存活不受这两种方法的影响。同样，BRN-3A 的过度表达会激活三叉神经元中的内源性 Bcl-2 基因，但不会激活交感神经元中的内源性 Bcl-2 基因。在胚胎发育过程中，神经生长因子撤除后，BRN-3A 对三叉神经元存活的保护作用显着增强。相比之下，相关因子 BRN-3B 的过度表达仅在胚胎发育的早期阶段增强三叉神经元的存活率。因此，BRN-3A（在某些情况下，BRN-3B）可以促进神经生长因子依赖性感觉神经元的存活，但不能促进交感神经元的存活，从而使其能够在发育中和成年神经系统中的一些（但不是全部）神经元群体的存活中发挥直接作用。
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.