CAS Key Lab for Biological Effects of Nanomaterials and Nanosafety, National Center for NanoScience and Technology, 11 BeiYiTiao, ZhongGuanCun, Beijing 100190, P. R. China.
Integr Biol (Camb). 2013 Oct;5(10):1244-52. doi: 10.1039/c3ib40131f.
Axon branching enables neurons to contact with multiple targets and respond to their microenvironment. Owing to its importance in neuronal network formation, axon branching has been studied extensively during the past decades. The chemical properties of extracellular matrices have been proposed to regulate axonal development, but the effects of their density changes on axon branching are not well understood. Here, we demonstrate that both the sharp broadening of substrate geometry and the sharp change of laminin density stimulate axon branching by using microcontact printing (μCP) and microfluidic printing (μFP) techniques. We also found that the change of axon branching stimulated by laminin density depends on myosin II activity. The change of laminin density induces asymmetric extensions of filopodia on the growth cone, which is the precondition for axon branching. These previously unknown mechanisms of change of laminin density-stimulated axon branching may explain how the extracellular matrices regulate axon branching in vivo and facilitate the establishment of neuronal networks in vitro.
轴突分支使神经元能够与多个靶标接触并响应其微环境。由于其在神经元网络形成中的重要性，轴突分支在过去几十年中得到了广泛的研究。细胞外基质的化学性质被认为可以调节轴突的发育，但它们密度变化对轴突分支的影响还不是很清楚。在这里，我们使用微接触印刷（μCP）和微流控印刷（μFP）技术证明了基底几何形状的急剧变宽和层粘连蛋白密度的急剧变化都可以刺激轴突分支。我们还发现，层粘连蛋白密度刺激的轴突分支的变化取决于肌球蛋白 II 的活性。层粘连蛋白密度的变化诱导生长锥上丝状伪足的不对称延伸，这是轴突分支的前提条件。这些关于层粘连蛋白密度刺激轴突分支变化的未知机制可以解释细胞外基质如何在体内调节轴突分支，并促进体外神经元网络的建立。
