TENSION AS A REGULATOR AND INTEGRATOR OF AXONAL GROWTH
TENSION AS A REGULATOR AND INTEGRATOR OF AXONAL GROWTH
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DOI：
10.1002/cm.970170103
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发表时间：
1990-01-01
影响因子：
--
通讯作者：
BUXBAUM, RE
中科院分区：
文献类型：
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作者：
HEIDEMANN, SR;BUXBAUM, RE
如上所述，长期以来人们一直认识到，物理力是形态发生整合的重要机制。尽管与生物特异性相比，生物整合只得到适度的实验关注，但这类工作奠定了一些重要进展的基础。例如，Steinberg[19781]的差异粘附假说应用表面张力的概念，将单个分子粘附事件整合到一个整体的形态发生机制中，解释组织发生的广泛方面。在动物体内，胶原蛋白组织成各种不同的结构元素依赖于周围细胞施加的力[Stopak等]。, 19851年。同样，内皮细胞形成毛细血管也依赖于细胞施加的张力和底物承受力的能力之间的平衡[Ingber和Folkman， 1989a]。我们自己的工作集中在轴突伸长，其中生长，即质量增加，与生长锥的运动推进密切相关。我们认为，这是由生长锥体作为生长的“第二信使”而产生的机械张力的结果。也就是说，张力似乎是调节轴突伸长和收缩的化学反应的信息来源，最明显的是伴随轴突长度变化的微管组装和拆卸。这种调节机制似乎以一种相当优雅的方式与肌动蛋白和微管的结构功能结合在一起。肌动蛋白处于张力状态，部分由微管在压缩状态下支撑；这种互补力的相互作用导致了一种热力学机制，将向前运动与微管组装联系起来，有趣的是，这与巴克明斯特·富勒（Buckminster Fuller）的“张拉整体”结构的基本原理相对应。张力可能调节轴突伸长的第一个证据来自Ross Harrison对轴突伸长的初步实验研究。大约50年前，Paul Weiss[1994]将神经元生长的过程分为三个阶段，这在今天仍然完全适用。前两个阶段，“开拓”和“应用”是由生长锥体活动介导的，但最后一个阶段，“牵引”生长阶段（轴突与目标突触后的轴突伸长）是由胚胎的扩张控制的。据推测，这种伸长是由靶的移出所施加的张力所调节的。尽管轴突生长的这一阶段对周围神经元的轴突长度有很大影响，但它在很大程度上被忽视了，直到Dennis Bray[19791]间接表明，培养神经元的神经突（轴突）处于张力状态，我们最近用细胞力学测量对这一结果进行了量化[Dennerll等]。, 19881年。Bray随后[1984]证实，张力是一种真正的生长刺激物，通过适当节奏的马达牵引神经突，引起超微结构正常的轴突伸长。这些结果加强了这样一种观点，即生长锥介导的伸长也反映了张力通过拉动生长锥刺激的生长。
As the quote above indicates, it has long been appreciated that physical force provides an important mechanism for integration in morphogenesis. Although biological integration receives only modest experimental attention compared with biological specificity, such work underlies some important advances. For example, Steinberg’s [19781 differential adhesion hypothesis applies notions of surface tension to integrate individual molecular adhesion events into an overall morphogenetic mechanism explaining broad aspects of histogenesis. The organization of collagen into a wide variety of different structural elements in animal bodies is dependent on the forces exerted by surrounding cells [Stopak et a]., 19851. Similarly, the formation of blood capillaries by endothelial cells is dependent on the balance between tension exerted by the cells and the ability of the substrate to withstand the force [Ingber and Folkman, 1989a]. Our own work has focussed on axonal elongation in which growth, ie, mass addition, is closely integrated with the motile advance of the growth cone. We suggest that this is the result of the mechanical tension generated by the advancing growth cone acting as a “second messenger” for growth. That is, tension appears to be a source of information regulating the chemical reactions of axonal elongation and retraction, most notably the microtubule assembly and disassembly accompanying axonal length changes. This regulatory t3 1990 Wiley-Liss, Inc. mechanism seems to be integrated with the structural function of actin and microtubules in a rather elegant way. Actin is under tension supported in part by microtubules under compression; this complementary force interaction leads to a thermodynamic mechanism connecting forward motility with microtubule assembly and, interestingly, corresponds to the basic principle of Buckminster Fuller’s “tensegrity” architecture. The first evidence that tension might regulate axonal elongation came from the initial experimental investigations of axonal elongation by Ross Harrison. AI-most 50 years ago, Paul Weiss [I9411 divided the process of neuronal growth into three phases that remain entirely relevant today. The first two phases,“pioneering” and “application,” are mediated by growth cone activity, but the final,“towing,” phase of growth (axonal elongation after the axon synapses with its target) is controlled by the expansion of the embryo. Presumably this elongation is regulated by the tension exerted by emigration of the target. Although this phase of axonal growth is responsible for much of the axonal length in peripheral neurons, it was largely ignored until Dennis Bray [19791 showed indirectly that neurites (axons) of cultured neurons were under tension, a result we recently quantified with cytomechanical measurements [Dennerll et a]., 19881. Bray subsequently [1984] confirmed that tension was a bona fide stimulator for growth by towing neurites with an appropriately paced motor to elicit ultrastructurally normal axonal elongation. These results strengthened the view that growth cone-mediated elongation also reflected tension stimulated growth via a pulling growth cone.