Neuronal Polarity and Morphogenesis

F. Lafont, A. Joliot, F. Perez, A. Prochiantz
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Abstract

Abstract For a given neuron, the development of its axonal and dendritic arborizations depends on many external factors, such as matrix molecules, growth factors, depolarization, electric fields, and adhesion molecules. In this paper, we summarize and comment on several protocols that can be used to modulate axonal or dendritic elongation and/or modify the shape of the neurites. A first series of protocols is based on the modulation of neuron-substratum adhesion by the addition of extra cellular matrix molecules. Indeed, axons initiate and elongate under low adhesion conditions, whereas dendrites grow only on highly adhesive substrata. A second series of protocols involves the use of drugs affecting the organization of the cytoskeleton. They suggest that the different behaviors of the axonal and dendritic compartments, in particular under low adhesion conditions, are due partly to the organization of the microtubule and actin networks. Third, we describe a protocol based on the internalization of Antennapedia homeodomain that translocates through the cell membrane and is conveyed to neuronal nuclei. Using this technique, we demonstrated that homeoproteins are involved in the morphological differentiation of postmitotic neurons and, in the case of the motoneurons, in axonal elongation. Furthermore, fusion polypeptides up to 109 amino acids and encompassing the 60-amino-acid translocating homeodomain are also transported through the membrane, thus offering a way to introduce exogenous biologically active peptides into live neurons.
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神经元极性和形态发生
对于一个给定的神经元,其轴突和树突分支的发育取决于许多外部因素,如基质分子、生长因子、去极化、电场和粘附分子。在本文中,我们总结和评论了几种可用于调节轴突或树突伸长和/或修改神经突形状的方案。第一个系列的协议是基于调制神经元基质粘附通过添加额外的细胞基质分子。事实上,轴突在低黏附条件下启动和拉长,而树突只在高黏附的基质上生长。第二套方案涉及使用影响细胞骨架组织的药物。他们认为,轴突和树突室的不同行为,特别是在低粘附条件下,部分是由于微管和肌动蛋白网络的组织。第三,我们描述了一种基于天线基同源结构域内化的方案,该结构域通过细胞膜易位并传递到神经元核。使用这种技术,我们证明了同型蛋白参与有丝分裂后神经元的形态分化,在运动神经元的情况下,参与轴突伸长。此外,多达109个氨基酸和包含60个氨基酸易位同源结构域的融合多肽也可以通过膜运输,从而提供了一种将外源生物活性肽引入活神经元的方法。
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