Drosophila growth cones: A genetically tractable platform for the analysis of axonal growth dynamics

Drosophila growth cones: A genetically tractable platform for the analysis of axonal growth dynamics
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果蝇生长锥:用于分析轴突生长动态的遗传易处理平台

DOI:
10.1002/dneu.20762
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发表时间:
2009
影响因子:
3
通讯作者:
A. Prokop
A. Prokop
中科院分区:
医学3区
文献类型:
--
作者:
N. Sánchez;C. Gonçalves;Robin Beaven;Ulrike Haessler;L. Ofner;C. Ballestrem;A. Prokop

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在发育和再生过程中,神经元网络的形成需要轴突沿着沿着可再生的路径向其适当的突触后靶细胞生长。轴突延伸发生在轴突尖端的生长锥(GC)处。GC推进和导航需要它们的细胞骨架网络的活性,包括板状伪足和丝状伪足中的丝状肌动蛋白(F-肌动蛋白)以及从轴突核心束发出的动态微管(MT)。控制这两种细胞骨架网络的分子机制,它们的相互作用,以及它们对细胞外信号线索的反应只有部分了解,这阻碍了我们对GC行为如何控制的概念性理解。在这里,我们介绍果蝇GC作为一个合适的模型来解决这些机制。果蝇GC的形态学和细胞骨架读数与其他模型(包括哺乳动物)相似,如本文所示,MT和F‐actin动力学、轴突生长速率、丝状伪足结构和运动性、MT网络的组织原理和亚细胞标记定位。因此,我们期望在果蝇中获得的基本见解可以转化为脊椎动物生物学。果蝇模型优于其他模型的优势在于它对组合遗传学的巨大适应性,作为解决轴突生长调控网络复杂性的有力策略。因此,使用药理学和遗传操作,我们证明了肌动蛋白细胞骨架的作用,在一个特定形式的MT组织(环的形成),已知调节GC暂停行为。我们证明这些事件是由肌动蛋白-MT连接因子短终止介导的,从而确定了在这种情况下的一个重要分子。© 2009威利期刊公司.开发神经生物学2010
The formation of neuronal networks, during development and regeneration, requires outgrowth of axons along reproducible paths toward their appropriate postsynaptic target cells. Axonal extension occurs at growth cones (GCs) at the tips of axons. GC advance and navigation requires the activity of their cytoskeletal networks, comprising filamentous actin (F‐actin) in lamellipodia and filopodia as well as dynamic microtubules (MTs) emanating from bundles of the axonal core. The molecular mechanisms governing these two cytoskeletal networks, their cross‐talk, and their response to extracellular signaling cues are only partially understood, hindering our conceptual understanding of how regulated changes in GC behavior are controlled. Here, we introduce Drosophila GCs as a suitable model to address these mechanisms. Morphological and cytoskeletal readouts of Drosophila GCs are similar to those of other models, including mammals, as demonstrated here for MT and F‐actin dynamics, axonal growth rates, filopodial structure and motility, organizational principles of MT networks, and subcellular marker localization. Therefore, we expect fundamental insights gained in Drosophila to be translatable into vertebrate biology. The advantage of the Drosophila model over others is its enormous amenability to combinatorial genetics as a powerful strategy to address the complexity of regulatory networks governing axonal growth. Thus, using pharmacological and genetic manipulations, we demonstrate a role of the actin cytoskeleton in a specific form of MT organization (loop formation), known to regulate GC pausing behavior. We demonstrate these events to be mediated by the actin‐MT linking factor Short stop, thus identifying an essential molecular player in this context. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2010
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