Ensor E, Smith M D, Latchman D S
Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom.
J Biol Chem. 2001 Feb 16;276(7):5204-12. doi: 10.1074/jbc.M007068200. Epub 2000 Oct 25.
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.
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体内特定神经元缺失。在此，我们首次证明了BRN-3A对神经元细胞存活具有直接作用。具体而言，在培养的三叉神经节或背根神经节感觉神经元中过表达BRN-3A，可增强它们在神经生长因子撤除后的存活能力。此外，降低BRN-3A水平会损害这些神经元的存活。两种方法均未影响交感神经元的存活。同样，BRN-3A的过表达激活了三叉神经元中的内源性Bcl-2基因，但未激活交感神经元中的该基因。在胚胎发育过程中，BRN-3A对神经生长因子撤除后三叉神经元存活的保护作用显著增强。相比之下，相关因子BRN-3B的过表达仅在胚胎发育早期增强了三叉神经元的存活能力。因此，BRN-3A（在某些情况下还有BRN-3B）可促进依赖神经生长因子的感觉神经元而非交感神经元的存活，使其在发育中和成年神经系统中某些（但并非所有）神经元群体的存活中发挥直接作用。
