Glia engulf degenerating axons during developmental axon pruning
Glia engulf degenerating axons during developmental axon pruning
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DOI：
10.1016/j.cub.2004.03.035
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发表时间：
2004-04-20
期刊：
影响因子：
9.2
通讯作者：
Luo, LQ
中科院分区：
文献类型：
--
作者：
Watts, RJ;Schuldiner, O;Luo, LQ
发育性轴突修剪广泛应用于神经系统的构建。因此，不同的机制可能用于各种形式的轴突修剪[1-7]。在果蝇蘑菇体（MB），γ神经元最初延伸到背侧和内侧MB轴突叶幼虫的轴突分支。在变态过程中，通过一系列精心策划的发育事件，两个叶的轴突分支在成年连接形成之前退化[6，8]。在这里，我们分析了超微结构的变化轴突修剪使用遗传编码的电子显微镜（EM）标记选择性标记γ神经元。通过抑制轴突修剪结合使用这个EM标记，我们证明了观察到的细胞事件和轴突修剪之间的因果关系。这些事件包括轴突超微结构的变化，突触变性，以及变性轴突片段被神经胶质细胞吞噬，随后通过内体-溶酶体途径分解。有趣的是，神经胶质细胞选择性地侵入MB轴突叶在变态的发病，这种细胞数量的增加是独立的轴突碎片。我们的研究揭示了神经胶质细胞在发育轴突修剪过程中去除轴突片段的关键作用。
Developmental axon pruning is widely used in constructing the nervous system. Accordingly, diverse mechanisms are likely employed for various forms of axon pruning [1-7]. In the Drosophila mushroom bodies (MB),gamma neurons initially extend axon branches into both the dorsal and medial MB axon lobes in larvae. Through a well-orchestrated set of developmental events during metamorphosis, axon branches to both lobes degenerate prior to the formation of adult connections [6,8]. Here, we analyze ultrastructural changes underlying axon pruning by using a genetically encoded electron microscopic (EM) marker to selectively label gamma neurons. By inhibiting axon pruning in combination with the use of this EM marker, we demonstrate a causal link between observed cellular events and axon pruning. These events include changes in axon ultrastructure, synaptic degeneration, and engulfment of degenerating axon fragments by glia for their subsequent breakdown via the endosomal-lysosomal pathway. Interestingly, glia selectively invade MB axon lobes at the onset of metamorphosis; this increase in cell number is independent of axon fragmentation. Our study reveals a key role for glia in the removal of axon fragments during developmental axon pruning.