Contrasting developmental axon regrowth and neurite sprouting of Drosophila mushroom body neurons reveals shared and unique molecular mechanisms
Contrasting developmental axon regrowth and neurite sprouting of Drosophila mushroom body neurons reveals shared and unique molecular mechanisms
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果蝇蘑菇体神经元的发育轴突再生和神经突萌发的对比揭示了共享和独特的分子机制
DOI：
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发表时间：
2016
影响因子：
3
通讯作者：
Oren Schuldiner
中科院分区：
文献类型：
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作者：
Neta Marmor;Oren Schuldiner
在发育过程中或损伤后调节内在轴突生长潜力的分子机制尽管非常重要，但在很大程度上仍不清楚。在这里，我们建立了原代培养的蘑菇体（MB）神经元的轴突发芽测定。我们使用MARCM技术标记和操纵MB神经元，使我们能够量化单个WT和突变体神经元的萌芽能力，这些神经元来自不同发育阶段的果蝇。分离的MB神经元的发芽依赖于WND，DLK直系同源物，轴突再生所需的保守基因。接下来，正如预期的那样，我们发现成年MB神经元的发芽能力显著降低。相反，令我们惊讶的是，我们发现蛹衍生的神经元与幼虫衍生的神经元相比表现出增加的发芽，这表明存在升高的生长潜力状态。然后，我们将神经突发芽的分子要求与MB神经元的发育轴突再生长进行了对比，我们先前已经证明，这一过程需要核受体UNF通过雷帕霉素（TOR）通路的靶点发挥作用。引人注目的是，我们发现虽然TOR是神经突发芽所需的，但UNF不是。相反，我们发现PTEN抑制成年神经元的发芽，这表明TOR在发芽过程中受到PI 3 K/PTEN通路的调节，在发育再生过程中受到UNF的调节。有趣的是，PI 3 K通路以及Wnd不需要发育再生，也不需要初始轴突生长，这表明轴突生长在电路形成，重塑和再生过程中共享一些分子组分，但在其他方面不同。© 2015威利期刊公司.开发神经生物学76：262-276，2016年
The molecular mechanisms regulating intrinsic axon growth potential during development or following injury remain largely unknown despite their vast importance. Here, we have established a neurite sprouting assay of primary cultured mushroom body (MB) neurons. We used the MARCM technique to both mark and manipulate MB neurons, enabling us to quantify the sprouting abilities of single WT and mutant neurons originating from flies at different developmental stages. Sprouting of dissociated MB neurons was dependent on wnd, the DLK ortholog, a conserved gene that is required for axon regeneration. Next, and as expected, we found that the sprouting ability of adult MB neurons was significantly decreased. In contrast, and to our surprise, we found that pupal‐derived neurons exhibit increased sprouting compared with neurons derived from larvae, suggesting the existence of an elevated growth potential state. We then contrasted the molecular requirements of neurite sprouting to developmental axon regrowth of MB ɣ neurons, a process that we have previously shown requires the nuclear receptor UNF acting via the target of rapamycin (TOR) pathway. Strikingly, we found that while TOR was required for neurite sprouting, UNF was not. In contrast, we found that PTEN inhibits sprouting in adult neurons, suggesting that TOR is regulated by the PI3K/PTEN pathway during sprouting and by UNF during developmental regrowth. Interestingly, the PI3K pathway as well as Wnd were not required for developmental regrowth nor for initial axon outgrowth suggesting that axon growth during circuit formation, remodeling, and regeneration share some molecular components but differ in others. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 262–276, 2016
突触小泡池消耗和补充的模型可以解释听觉神经纤维自发尖峰序列的尖峰间隔分布和非更新特性
DOI：
10.1523/jneurosci.0903-14.2014
发表时间：
2014
期刊：
The Journal of Neuroscience
影响因子：
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作者：
Peterson AJ;Irvine DR;Heil P
通讯作者：
Heil P