Substrate three-dimensionality induces elemental morphological transformation of sensory neurons on a physiologic timescale.
Substrate three-dimensionality induces elemental morphological transformation of sensory neurons on a physiologic timescale.
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基质的三维性在生理时间尺度上诱导感觉神经元的基本形态转变。
DOI：
10.1089/ten.tea.2011.0221
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发表时间：
2012
影响因子：
--
通讯作者：
Leach,JennieB
中科院分区：
文献类型：
--
作者：
Ribeiro,Andreia;Vargo,Shelby;Powell,ElizabethM;Leach,JennieB
神经元的自然环境是三维（3D）组织。在体内，胚胎感觉神经元在出生前经历细胞质和细胞骨架重排到更成熟的伪单极轴突乔木之前，短暂地表达具有两个相对的神经突的两极形态。单极形态对于成年人从外周神经系统到中枢神经系统的正确信息传递至关重要。在二维（2D）衬底上，这种转化明显延迟或不存在。我们报告说，3D培养平台可以在与体内相似的时间框架内调用单极轴突轴的特征转化，克服了在2D基质中失去这一重要里程碑。此外，3D基质单独提供了促进轴突分支特征的环境，这些特征反映了在体内观察到的形态模式。我们还通过在神经生长因子（NGF）存在和缺失的情况下培养神经元，分析了可溶性线索在这些形态形成过程中的参与情况。NGF是一种在周围和中枢神经系统的发育中起着独特作用的分子。不含NGF的2D和3D培养与含有NGF的培养相比，单极神经元的相对数量显著减少，神经突长度更短，分支点更少。有趣的是，不含NGF的3D培养神经元的分支特征与含NGF的2D培养神经元相似。因此，在没有NGF的3D环境中培养的神经元失去了向单极神经元分化的能力，这表明这种形态标志不仅需要像NGF这样的可溶性线索的呈现，还需要周围的粘附配体的3D呈现，以实现先天形态形成程序。我们提出，在三维环境中，各种基质和可溶性线索呈现在细胞的所有表面；这种优化的环境允许神经元精心设计其真实的表型，并遵循神经元固有的程序指令，但当细胞从胚胎中分离出来时，这些指令被破坏了。因此，本研究提供的定量数据支持3D基质对于维持神经元的体内发育和破译设计神经生成和修复的生物材料支架所需的信号机制至关重要。
The natural environment of a neuron is the three-dimensional (3D) tissue.In vivo, embryonic sensory neurons transiently express a bipolar morphology with two opposing neurites before undergoing cytoplasmic and cytoskeletal rearrangement to a more mature pseudo-unipolar axonal arbor before birth. The unipolar morphology is crucial in the adult for correct information transmission from the periphery to the central nervous system. On two-dimensional (2D) substrates this transformation is delayed significantly or absent. We report that a 3D culture platform can invoke the characteristic transformation to the unipolar axonal arbor within a time frame similar toin vivo, overcoming the loss of this essential milestone in 2D substrates. Additionally, 3D substrates alone provided an environment that promoted axonal branching features that reflect morphological patterns observedin vivo. We have also analyzed the involvement of soluble cues in these morphogenic processes by culturing the neurons in the presence and absence of nerve growth factor (NGF), a molecule that plays distinct roles in the development of the peripheral and central nervous systems. Without NGF, both 2D and 3D cultures had significant decreases in the relative population of unipolar neurons as well as shorter neurite lengths and fewer branch points compared to cultures with NGF. Interestingly, branching features of neurons cultured in 3D without NGF resemble those of neurons cultured in 2D with NGF. Therefore, neurons cultured in 3D without NGF lost the ability to differentiate into unipolar neurons, suggesting that this morphological hallmark requires not only presentation of soluble cues like NGF, but also the surrounding 3D presentation of adhesive ligands to allow for realization of the innate morphogenic program. We propose that in a 3D environment, various matrix and soluble cues are presented toward all surfaces of the cell; this optimized milieu allows neurons to elaborate their genuine phenotype and follow programmed instructions that are intrinsic to the neuron, but disrupted when cells were dissected from the embryo. Thus, this study presents quantitative data supporting that 3D substrates are critical for sustaining thein vivoontogeny of neurons and deciphering signaling mechanisms necessary for designing biomaterial scaffolds for nerve generation and repair.
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