Integration of topographical and biochemical cues by axons during growth on microfabricated 3-D substrates
Integration of topographical and biochemical cues by axons during growth on microfabricated 3-D substrates
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DOI：
10.1016/j.yexcr.2005.10.007
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发表时间：
2005-12-10
影响因子：
3.7
通讯作者：
Folch, A
中科院分区：
文献类型：
--
作者：
Li, NZ;Folch, A
在胚胎神经发育过程中，轴突尖端（“生长锥”）通过可溶性的趋化因子和存在于细胞外基质和周围细胞表面的固定的、允许生长或抑制生长的接触线索引导通过动态的三维（3-D）景观。利用传统的二维（2-D）衬底来探测生长锥在三维导航过程中响应多个接触线索的搜索算法是很困难的。在这里，我们提出了一项体外研究，在该研究中，小鼠胚胎皮层神经元的轴突受到竞争生长选择的挑战，使用具有允许性和微地形变化的3-D基质。作为三维基底，我们在聚二甲基硅氧烷（PDMS）的微加工步骤和Matrigel的互补特征上使用聚d -赖氨酸（PDL）涂层。我们发现轴突表现出对PDL的偏好，而不是对Matrigel的偏好，并且在与生长锥的探索范围一致的距离内，轴突表现出对最直路径的偏好。当这两种偏好发生冲突时，轴突选择直接长成矩阵；当直线路径不允许时，轴突向转角最小的方向转动。这些结果表明，生长锥通过整合容忍度和地形线索来做出三维导航决策。(c) 2005爱思唯尔公司版权所有。
During embryonic neural development, axon tips ("growth cones") are guided through a dynamic three-dimensional (3-D) landscape by soluble chemotropic factors and by immobilized, growth-permissive or growth-inhibiting contact cues present in the extracellular matrix and on the surface of surrounding cells. It has been difficult to probe the search algorithms of growth cones in response to multiple contact cues during 3-D navigation using traditional two-dimensional (2-D) substrates. Here, we present an in vitro study in which the axons of murine embryonic cortical neurons are challenged with competing growth options, using 3-D substrates that feature variations in permissiveness and microtopography. As 3-D substrates, we used poly-D-lysine (PDL) coatings on microfabricated steps of polydimethylsiloxane (PDMS) and complementary features of Matrigel. We found that axons display a preference for PDL over Matrigel and for the straightest path within a distance consistent with the exploratory range of the growth cone. When these two preferences are in conflict, axons choose to grow straight into Matrigel; when the straight path is not permissive, the axon turns in the direction that minimizes the turning angle. These results suggest that growth cones make 3-D navigation decisions by integrating permissiveness and topographical cues. (c) 2005 Elsevier Inc. All rights reserved.