Hui K, Kucera J, Henderson J T
Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada.
Cell Death Differ. 2008 Apr;15(4):691-9. doi: 10.1038/sj.cdd.4402294. Epub 2007 Dec 21.
Proper development of the nervous system requires that a carefully controlled balance be maintained between both proliferation and neuronal survival. The process of programmed cell death is believed to play a key role in regulating levels of neuronal survival, in large part through the action of antiapoptotic proteins, such as Bcl-2. Consistent with this, Bcl-2 has been shown to be a key regulator of apoptotic signaling in post-mitotic neurons. However, we still know remarkably little regarding the role that Bcl-2 plays in regulating the survival of specific motor neuron populations. In the present study, we have examined somatic motor neurons of the lumbar spinal cord, and branchiomotor neurons of the facial nucleus in bcl-2-null mice to determine the differential dependence among motor neuron populations with respect to Bcl-2-mediated survival. Examination of neuronal and axon number, axonal area, and the distribution of axonal loss in bcl-2-null mice demonstrates that, in contrast to the great majority of alpha motor neurons, gamma motor neurons exhibit a unique dependence upon bcl-2 for survival. These results demonstrate, for the first time, the connection between Bcl-2 expression, motor neuron survival, and the establishment of different motor populations.
神经系统的正常发育需要在细胞增殖和神经元存活之间保持精确控制的平衡。程序性细胞死亡过程被认为在调节神经元存活水平方面起着关键作用，这在很大程度上是通过抗凋亡蛋白（如Bcl-2）的作用实现的。与此一致的是，Bcl-2已被证明是有丝分裂后神经元凋亡信号的关键调节因子。然而，我们对Bcl-2在调节特定运动神经元群体存活中所起的作用仍知之甚少。在本研究中，我们检查了bcl-2基因敲除小鼠腰脊髓的躯体运动神经元和面神经核的鳃运动神经元，以确定运动神经元群体对Bcl-2介导的存活的差异依赖性。对bcl-2基因敲除小鼠的神经元和轴突数量、轴突面积以及轴突损失分布的检查表明，与绝大多数α运动神经元不同，γ运动神经元的存活对bcl-2具有独特的依赖性。这些结果首次证明了Bcl-2表达、运动神经元存活以及不同运动群体建立之间的联系。
