Tanaka H, Landmesser L T
J Neurosci. 1986 Oct;6(10):2889-99. doi: 10.1523/JNEUROSCI.06-10-02889.1986.
The quantitative matching hypothesis of neuronal cell death was tested for the chick hindlimb by determining the relationship between myotube number at the onset of motoneuron cell death and the number of motoneurons that survive in chicks, quail, and chick-quail chimeras. Hindlimb buds, which differ in size between the 2 species, were exchanged at stages 16 1/2-19, myosin ATPase-stained myotubes in selected thigh muscles were counted during the cell death period (stages 30-34), and lumbosacral motoneurons were counted following the cell death period (stage 38). No quail motoneurons were rescued when quail cords innervated chick limbs. When chick cords innervated quail limbs, the number of surviving motoneurons was significantly decreased but not to quail values. We consider that this occurred because chicks develop more slowly than quail, and we found that transplanted chick limbs were developmentally younger than the contralateral quail limb at the onset of motoneuron cell death and contained fewer myotubes. Similarly, transplanted quail limbs contained more myotubes at the onset of cell death than normal stage 30 quail limbs. An excellent correlation was obtained during normal development of both species between the number of myotube clusters at the onset of cell death and the number of surviving motoneurons. This correlation was also observed for chick-quail chimeras, and when the data points were plotted for control chick, control quail, chick host-quail limb, and quail host-chick limb, the correlation coefficient was 0.996. This strongly suggests that some parameter closely related to myotube number limits the number of motoneurons that will survive. A proposal consistent with our observations is that motoneuron survival is dependent on the uptake of a myotube-derived trophic factor that can only be taken up at synaptic sites and that the number of such sites is limited and directly related to myotube number. In conclusion, our observations strongly support a quantitative-matching component in the process of neuronal cell death. However, since we were unable to rescue any neurons, we cannot exclude the possibility that some proportion of neurons normally dies for reasons other than peripheral competition.
通过确定运动神经元细胞死亡开始时肌管数量与鸡、鹌鹑以及鸡 - 鹌鹑嵌合体中存活运动神经元数量之间的关系，对鸡后肢神经元细胞死亡的定量匹配假说进行了测试。在第16 1/2 - 19阶段交换了两种物种间大小不同的后肢芽，在细胞死亡期（第30 - 34阶段）对选定大腿肌肉中经肌球蛋白ATP酶染色的肌管进行计数，并在细胞死亡期之后（第38阶段）对腰骶部运动神经元进行计数。当鹌鹑脊髓支配鸡的肢体时，没有鹌鹑运动神经元得到挽救。当鸡的脊髓支配鹌鹑的肢体时，存活运动神经元的数量显著减少，但未降至鹌鹑的数值。我们认为出现这种情况是因为鸡的发育比鹌鹑慢，并且我们发现移植的鸡肢体在运动神经元细胞死亡开始时在发育上比同侧鹌鹑肢体更年轻，且含有更少的肌管。同样，移植的鹌鹑肢体在细胞死亡开始时比正常的第30阶段鹌鹑肢体含有更多的肌管。在两个物种的正常发育过程中，细胞死亡开始时肌管簇的数量与存活运动神经元的数量之间获得了极好的相关性。在鸡 - 鹌鹑嵌合体中也观察到了这种相关性，并且当为对照鸡、对照鹌鹑、鸡宿主 - 鹌鹑肢体和鹌鹑宿主 - 鸡肢体绘制数据点时，相关系数为0.996。这有力地表明，与肌管数量密切相关的某些参数限制了将存活的运动神经元数量。与我们的观察结果一致的一种推测是，运动神经元的存活依赖于对一种肌管衍生的营养因子的摄取，这种营养因子只能在突触部位被摄取，并且此类部位的数量是有限的且与肌管数量直接相关。总之，我们的观察结果有力地支持了神经元细胞死亡过程中的定量匹配成分。然而，由于我们无法挽救任何神经元，我们不能排除正常情况下一些神经元因外周竞争以外的原因死亡的可能性。
