Putting the model to the test: are APC proteins essential for neuronal polarity, axon outgrowth, and axon targeting?

Putting the model to the test: are APC proteins essential for neuronal polarity, axon outgrowth, and axon targeting?
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将模型投入测试:APC蛋白对于神经元极性,轴突的生长和轴突靶向是否必不可少?

DOI:
10.1083/jcb.200807079
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发表时间:
2008-10-20
影响因子:
7.8
通讯作者:
Peifer, Mark
Peifer, Mark
中科院分区:
生物学1区
文献类型:
--
作者:
Rusan, Nasser M.;Akong, Kathryn;Peifer, Mark

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神经元的高度极化结构对它们的功能很重要。基于显性-负性方法的实验数据表明,肿瘤抑制因子腺瘤性息肉病结肠(APC)是Wnt信号和细胞骨架的调节者,调节神经外胚层前体和神经元的极性,帮助指定一个轴突作为轴突,促进其生长,并指导轴突路径。然而,这种显性-消极的方法可能会影响到APC不是必不可少的过程。我们从果蝇幼虫神经前体和神经元中完全去除了APC,测试APC是否在神经元极性中发挥普遍作用。令人惊讶的是,APC对于不对称的细胞分裂或中央脑(CB)神经母细胞的固定分裂轴并不是必需的,尽管它们确实影响细胞周期进程和纺锤体结构。同样,CB、小叶栓和蘑菇体神经元不需要APC来极化、轴突生长,或者在后两种情况下,轴突靶向。这些数据表明,应该使用功能丧失工具重新评估哺乳动物APC所扮演的细胞骨架角色。
The highly polarized architecture of neurons is important for their function. Experimental data based on dominant-negative approaches suggest that the tumor suppressor adenomatous polyposis coli (APC), a regulator of Wnt signaling and the cytoskeleton, regulates polarity of neuroectodermal precursors and neurons, helping specify one neurite as the axon, promoting its outgrowth, and guiding axon pathfinding. However, such dominant-negative approaches might affect processes in which APC is not essential. We completely removed both APCs from Drosophila melanogaster larval neural precursors and neurons, testing whether APCs play universal roles in neuronal polarity. Surprisingly, APCs are not essential for asymmetric cell division or the stereotyped division axis of central brain (CB) neuroblasts, although they do affect cell cycle progression and spindle architecture. Likewise, CB, lobular plug, and mushroom body neurons do not require APCs for polarization, axon outgrowth, or, in the latter two cases, axon targeting. These data suggest that proposed cytoskeletal roles for APCs in mammals should be reassessed using loss of function tools.
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