Watts Ryan J, Schuldiner Oren, Perrino John, Larsen Camilla, Luo Liqun
Department of Biological Sciences, Stanford University, Stanford, CA 94305 USA.
Curr Biol. 2004 Apr 20;14(8):678-84. doi: 10.1016/j.cub.2004.03.035.
Developmental axon pruning is widely used in constructing the nervous system. Accordingly, diverse mechanisms are likely employed for various forms of axon pruning. 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. 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.
发育性轴突修剪在构建神经系统中广泛应用。因此，不同形式的轴突修剪可能采用了多种机制。在果蝇的蘑菇体（MB）中，γ神经元最初在幼虫期将轴突分支延伸至背侧和内侧MB轴突叶。在变态发育过程中，通过一系列精心编排的发育事件，在成年连接形成之前，两个叶的轴突分支都会退化。在这里，我们使用一种基因编码的电子显微镜（EM）标记物选择性地标记γ神经元，分析轴突修剪背后的超微结构变化。通过抑制轴突修剪并结合使用这种EM标记物，我们证明了观察到的细胞事件与轴突修剪之间存在因果关系。这些事件包括轴突超微结构的变化、突触退化以及神经胶质细胞对退化轴突片段的吞噬，随后通过内体-溶酶体途径将其分解。有趣的是，在变态发育开始时，神经胶质细胞选择性地侵入MB轴突叶；细胞数量的增加与轴突碎片化无关。我们的研究揭示了神经胶质细胞在发育性轴突修剪过程中去除轴突片段方面的关键作用。
