Engulfing action of glial cells is required for programmed axon pruning during Drosophila metamorphosis
Engulfing action of glial cells is required for programmed axon pruning during Drosophila metamorphosis
复制标题
DOI：
10.1016/j.cub.2004.04.001
复制
发表时间：
2004-04-20
期刊：
影响因子：
9.2
通讯作者：
Ito, K
中科院分区：
文献类型：
--
作者：
Awasaki, T;Ito, K
背景：轴突修剪参与功能性神经回路的建立和维持。在果蝇变态过程中，幼虫轴突的选择性修剪受蜕皮激素的发育调节，并由局部轴突变性引起。以前的研究揭示了触发这种修剪过程的内在分子和细胞机制，但修剪是如何完成的仍然是未知的。结果：对果蝇蘑菇体（MB）神经元轴突分支形态学变化的详细分析表明，在蛹早期，相邻的血管曲张簇，每个血管曲张簇属于不同的轴突，在局部轴突变性发作前不久同时消失。在这个阶段，轴突分支束被周围胶质细胞的突起浸润。这些过程吞噬静脉曲张簇并积累细胞内降解隔室。通过shibire的温度敏感等位基因选择性抑制神经胶质细胞的细胞功能，包括内吞作用，抑制神经胶质浸润和静脉曲张消除，并诱导轴突修剪严重延迟。选择性抑制MB神经元中的蜕皮激素受体严重抑制不仅轴突修剪，但也周围glial.Conclusions的浸润和吞噬行动：这些研究结果强烈表明，胶质细胞被激活的蜕皮激素刺激的MB神经元。这些神经胶质细胞浸润轴突分支的质量，以消除静脉曲张，并主动分解轴突分支，而不仅仅是清除已经降解的碎片。因此，我们建议，neuronglia相互作用是必不可少的精确协调的轴突修剪过程中果蝇变态。
Background: Axon pruning is involved in establishment and maintenance of functional neural circuits. During metamorphosis of Drosophila, selective pruning of larval axons is developmentally regulated by ecdysone and caused by local axon degeneration. Previous studies have revealed intrinsic molecular and cellular mechanisms that trigger this pruning process, but how pruning is accomplished remains essentially unknown.Results: Detailed analysis of morphological changes in the axon branches of Drosophila mushroom body (MB) neurons revealed that during early pupal stages, clusters of neighboring varicosities, each of which belongs to different axons, disappear simultaneously shortly before the onset of local axon degeneration. At this stage, bundles of axon branches are infiltrated by the processes of surrounding glia. These processes engulf clusters of varicosities and accumulate intracellular degradative compartments. Selective inhibition of cellular functions, including endocytosis, in glial cells via the temperature-sensitive allele of shibire both suppresses glial infiltration and varicosity elimination and induces a severe delay in axon pruning. Selective inhibition of ecdysone receptors in the MB neurons severely suppressed not only axon pruning but also the infiltration and engulfing action of the surrounding glia.Conclusions: These findings strongly suggest that glial cells are extrinsically activated by ecdysone-stimulated MB neurons. These glial cells infiltrate the mass of axon branches to eliminate varicosities and break down axon branches actively rather than just scavenging already-degraded debris. We therefore propose that neuronglia interaction is essential for the precisely coordinated axon-pruning process during Drosophila metamorphosis.