Mechanical tension as a regulator of axonal development.
Mechanical tension as a regulator of axonal development.
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DOI：
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发表时间：
1994
期刊：
影响因子：
3.4
通讯作者：
S. Heidemann;R. Buxbaum
中科院分区：
文献类型：
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作者：
S. Heidemann;R. Buxbaum
我们回顾了我们实验室过去6年的研究，这些研究表明，培养神经元轴突上的机械张力是轴突伸长和收缩的调节剂和刺激剂。使用校准的玻璃针测量或施加张力，我们已经积累了张力作为轴突发育四个不同阶段的调节器的直接证据：1)轴突起始；2)生长锥介导伸长；3)生长锥达到目标后生长；4)轴突收缩。我们的结果可以通过一个模型来总结，在这个模型中，张力水平表现为一个三位置控制器，就像一个双极双掷的电气开关。该开关的三种设置通过张力阈值来区分：1)在上阈值之上，张力作为刺激轴突伸长和起始的刺激物。神经突的生长速度与神经突上的张力大小成正比。类似程度的紧张可以引发小鸡感觉神经元的新生神经突。这些张力诱导的轴突在微管的轴向排列和生长锥的运动发育中是正常的。在正常生长条件下，我们的证据支持这样的观点，即生长锥通过充当牵引器，拉动神经突来刺激轴突伸长；2)“开关”也有轴突收缩的设置，这种情况发生在张力强度低于某些不同的较低张力阈值时。我们的证据表明，这种轴突缩回涉及由神经突轴产生的主动力；3)在两个阈值之间，开关处于中性位置，神经突被动表现为粘弹性固体。也就是说，神经突在张力作用下拉伸，但没有真正的生长，即没有微管组装或膜添加等。因此，张力似乎可以被视为一种“第二信使”，其水平调节轴突发育。发育性神经毒物的作用机制可能是改变张力的产生或对张力的敏感性。至少，机械力调节轴突生长的证据为研究神经毒性机制提供了新的途径。
We review studies from our laboratory over the last 6 years that indicate the mechanical tension on the axons of cultured neurons is a regulator and stimulator of axonal elongation and retraction. Using calibrated glass needles to measure or apply tension, we have accumulated direct evidence for tension as a regulator of four different phases of axonal development: 1) axonal initiation; 2) growth cone-mediated elongation; 3) growth after the growth cone reaches its target; and 4) axonal retraction. Our results can be summarized by a model in which tension levels behave as a three position controller, like a double-pole, double-throw electric switch. The three settings of this switch are separated by tension thresholds: 1) Above the upper threshold, tension acts as a stimulator for axonal elongation and initiation. The growth rate of the neurite is directly proportional to the magnitude of tension on the neurite. Similar levels of tension can initiate neurites de novo from chick sensory neurons. These tension-induced axons are normal in their axial array of microtubules and in the development of a motile growth cone. Under normal conditions of growth, our evidence supports the notion that the growth cone stimulates axonal elongation by acting as a tractor, pulling on the neurite; 2) The "switch" also has a setting for axonal retraction, which occurs at tension magnitudes below some different, lower tension threshold. Our evidence indicates that such axonal retraction involves active force generation by the neurite shaft; and 3) Between the two thresholds, the switch is in a neutral position and the neurite behaves passively as a viscoelastic solid. That is, the neurite stretches in response to tension but there is no true growth, i.e. no microtubule assembly or membrane addition etc. Thus, it seems tension can be regarded as a kind of "second messenger" whose level regulates axonal development. The mechanism of action of developmental neurotoxicants may be to alter the production of, or the sensitivity to, tension. At the least, this evidence that mechanical force regulates axonal growth provides a new avenue of investigation into neurotoxic mechanisms.