Brn-3a activates the expression of Bcl-xL and promotes neuronal survival in vivo as well as in vitro
Brn-3a activates the expression of Bcl-xL and promotes neuronal survival in vivo as well as in vitro
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DOI：
10.1006/mcne.2000.0927
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发表时间：
2001-03-01
影响因子：
3.5
通讯作者：
Latchman, DS
中科院分区：
文献类型：
--
作者：
Smith, MD;Melton, LA;Latchman, DS
细胞命运的决定在胚胎发生的后期和出生后早期起着关键作用，在此期间，大约一半的神经发生过程中出生的神经元经历程序性细胞死亡。先前有报道称IV型POU结构域转录因子Brn-3a在感觉神经元群体的成熟和存活中起作用。事实上，我们已经证明，长形式的Brn-3a能够激活抗凋亡Bcl-2基因的表达，并提高感觉神经元培养中的神经元存活率。在这项研究中，我们报道了另一个抗凋亡家族成员Bcl-x(L)作为Brn-3a在感觉神经元中的靶基因的鉴定，提供了Brn-3a在发育过程中决定感觉神经元命运的进一步机制。Brn-3a可激活Bcl-x(L)基因在感觉细胞中的表达，而在交感细胞中不表达；感觉神经元中Brn-3a表达的反义抑制使其表达减少。最重要的是，在完整动物坐骨神经损伤模型中，Bcl-x(L)的表达和神经元存活都通过在体内背根神经节中过表达Brn-3a而增强。
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-x(L), 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-x(L) 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-x(L) 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.