Sensory axon guidance with semaphorin 6A and nerve growth factor in a biomimetic choice point model.
Sensory axon guidance with semaphorin 6A and nerve growth factor in a biomimetic choice point model.
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DOI：
10.1088/1758-5082/6/3/035026
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发表时间：
2014-09
期刊：
影响因子：
9
通讯作者：
Moore MJ
中科院分区：
文献类型：
--
作者：
Curley JL;Catig GC;Horn-Ranney EL;Moore MJ
指导线索对体内轴突发育和再生的直接影响尚未完全了解，因为该过程涉及多种吸引和排斥信号，以可溶性和膜结合配体的形式存在。更好地理解轴突引导对于通过改善受损神经的生长和映射来恢复神经系统损伤后的功能至关重要。由于它们作为CNS再生抑制剂的影响，我们研究了脑信号蛋白6A和Ephrin-B3对E15大鼠背根神经节外植体的排斥特性，以及与化学吸引性神经生长因子的可溶性梯度的可能相互作用。我们采用了一个三维仿生体外选择点模型，这使得简单和快速的制备图案化的凝胶生长基质与可量化的指导线索在一个指定的方式，类似于在体内介绍可溶性和/或固定化配体。神经突表现出抑制性反应，固定Sema 6A腰骶DRG外植体，而没有这样的排斥固定Ephrin-B3在任何脊髓水平的外植体观察。有趣的是，Sema 6A抑制可以通过同时呈现可溶性NGF梯度以浓度依赖性方式部分减弱。本文所述的体外模型代表了在寻求理解发育过程和改善神经系统损伤后的再生中的通用和有价值的研究工具。
The direct effect of guidance cues on developing and regenerating axons in vivo is not fully understood, as the process involves a multiplicity of attractive and repulsive signals, presented both as soluble and membrane-bound ligands. A better understanding of axon guidance is critical to functional recovery following injury to the nervous system through improved outgrowth and mapping of damaged nerves. Due to their implications as inhibitors to CNS regeneration, we investigated the repulsive properties of Semaphorin 6A and Ephrin-B3 on E15 rat dorsal root ganglion explants, as well as possible interactions with soluble gradients of chemoattractive nerve growth factor. We employed a 3D biomimetic in vitro choice point model, which enabled the simple and rapid preparation of patterned gel growth matrices with quantifiable presentation of guidance cues in a specifiable manner that resembles the in vivo presentation of soluble and/or immobilized ligands. Neurites demonstrated an inhibitory response to immobilized Sema6A by lumbosacral DRG explants, while no such repulsion was observed for immobilized Ephrin-B3 by explants at any spinal level. Interestingly, Sema6A inhibition could be partially attenuated in a concentration-dependent manner through the simultaneous presentation of soluble NGF gradients. The in vitro model described herein represents a versatile and valuable investigative tool in the quest for understanding developmental processes and improving regeneration following nervous system injury.
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影响因子：
4.9
作者：
Curley, J. Lowry;Moore, Michael J.
通讯作者：
Moore, Michael J.
影响因子：
3.7
作者：
Lai Y;Cheng K;Kisaalita W
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Kisaalita W
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25
作者：
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作者：
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1.2
作者：
Curley, J. Lowry;Jennings, Scott R.;Moore, Michael J.
通讯作者：
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