Šmít Daniel, Fouquet Coralie, Pincet Frédéric, Zapotocky Martin, Trembleau Alain
Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Neuroscience Paris Seine - Institute of Biology Paris Seine, Sorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, Paris, France.
Elife. 2017 Apr 19;6:e19907. doi: 10.7554/eLife.19907.
While axon fasciculation plays a key role in the development of neural networks, very little is known about its dynamics and the underlying biophysical mechanisms. In a model system composed of neurons grown ex vivo from explants of embryonic mouse olfactory epithelia, we observed that axons dynamically interact with each other through their shafts, leading to zippering and unzippering behavior that regulates their fasciculation. Taking advantage of this new preparation suitable for studying such interactions, we carried out a detailed biophysical analysis of zippering, occurring either spontaneously or induced by micromanipulations and pharmacological treatments. We show that zippering arises from the competition of axon-axon adhesion and mechanical tension in the axons, and provide the first quantification of the force of axon-axon adhesion. Furthermore, we introduce a biophysical model of the zippering dynamics, and we quantitatively relate the individual zipper properties to global characteristics of the developing axon network. Our study uncovers a new role of mechanical tension in neural development: the regulation of axon fasciculation.
虽然轴突成束在神经网络的发育中起着关键作用，但人们对其动态变化及潜在的生物物理机制知之甚少。在一个由从胚胎小鼠嗅上皮外植体离体培养的神经元组成的模型系统中，我们观察到轴突通过其轴干彼此动态相互作用，导致拉链式和反拉链式行为，从而调节它们的成束。利用这种适合研究此类相互作用的新制备方法，我们对自发发生或由显微操作和药物处理诱导的拉链式行为进行了详细的生物物理分析。我们表明，拉链式行为源于轴突间粘附力与轴突中的机械张力之间的竞争，并首次对轴突间粘附力进行了量化。此外，我们引入了拉链式动态变化的生物物理模型，并将单个拉链特性与发育中的轴突网络的整体特征进行了定量关联。我们的研究揭示了机械张力在神经发育中的一个新作用：轴突成束的调节。
