Astrocytes play a key role in Drosophila mushroom body axon pruning.

Astrocytes play a key role in Drosophila mushroom body axon pruning.
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DOI:
10.1371/journal.pone.0086178
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Schuldiner O
Schuldiner O
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hakim Y;Yaniv SP;Schuldiner O

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轴突修剪是一种进化上保守的策略,用于在发育过程中重塑神经元连接。果蝇蘑菇体(MB)以高度刻板和严格调控的方式进行神经元重塑,但仍存在许多悬而未决的问题。尽管先前已经表明,胶质细胞通过分泌TGF-β配体肌胶凝蛋白来指导修剪,肌胶凝蛋白使MB神经元准备碎裂,并且一旦碎裂完成,随后还吞噬轴突碎片,但是哪些胶质细胞亚型参与这些过程以及分子细节是未知的。在这里,我们表明,出乎意料的是,星形胶质细胞是主要的神经胶质细胞亚型,负责清除MB轴突碎片碎片碎片后,即使他们只代表少数的神经胶质细胞在MB区域重塑。此外,我们表明,星形胶质细胞既促进MB轴突的碎片,以及明确的轴突碎片,这一过程是由蜕皮激素信号在星形胶质细胞本身介导的。此外,我们发现,阻断星形胶质细胞中细胞吞噬受体德雷珀的表达只影响轴突碎片的清除。因此,我们将星形胶质细胞促进轴突断裂的功能与在断裂完成后清除轴突碎片的功能分开。我们的研究发现了星形胶质细胞在MB中的新作用,并提出了两个独立的途径,它们影响发育轴突修剪。
Axon pruning is an evolutionarily conserved strategy used to remodel neuronal connections during development. The Drosophila mushroom body (MB) undergoes neuronal remodeling in a highly stereotypical and tightly regulated manner, however many open questions remain. Although it has been previously shown that glia instruct pruning by secreting a TGF-β ligand, myoglianin, which primes MB neurons for fragmentation and also later engulf the axonal debris once fragmentation has been completed, which glia subtypes participate in these processes as well as the molecular details are unknown. Here we show that, unexpectedly, astrocytes are the major glial subtype that is responsible for the clearance of MB axon debris following fragmentation, even though they represent only a minority of glia in the MB area during remodeling. Furthermore, we show that astrocytes both promote fragmentation of MB axons as well as clear axonal debris and that this process is mediated by ecdysone signaling in the astrocytes themselves. In addition, we found that blocking the expression of the cell engulfment receptor Draper in astrocytes only affects axonal debris clearance. Thereby we uncoupled the function of astrocytes in promoting axon fragmentation to that of clearing axonal debris after fragmentation has been completed. Our study finds a novel role for astrocytes in the MB and suggests two separate pathways in which they affect developmental axon pruning.
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