Astrocytes engage unique molecular programs to engulf pruned neuronal debris from distinct subsets of neurons.
Astrocytes engage unique molecular programs to engulf pruned neuronal debris from distinct subsets of neurons.
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星形胶质细胞涉及独特的分子程序，以吞噬不同神经元子集的修剪修剪的神经元碎片。
DOI：
10.1101/gad.229518.113
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发表时间：
2014-01-01
影响因子：
10.5
通讯作者：
Freeman MR
中科院分区：
文献类型：
--
作者：
Tasdemir-Yilmaz OE;Freeman MR
神经回路的组装包括最初的神经元和突触连接的过度产生，然后是它们的选择性消除。Tasdemir-Yilmaz和Freeman表明果蝇幼虫星形胶质细胞是蛹中枢神经系统中的主要吞噬细胞类型。MB γ神经元轴突通过德雷珀和Crk/Mbc/dCed-12信号通路被星形胶质细胞吞噬，而Crk/Mbc/dCed-12介导vCrz+神经突的消除，但德雷珀不介导。消除德雷珀信号延迟早期vCrz+神经突变性，表明神经胶质细胞通过吞噬信号促进神经突破坏。精确的神经回路组装是通过最初过度生产神经元和突触，然后通过消除旺盛的神经元和突触进行改进来实现的。神经胶质细胞是负责清除神经元碎片的主要细胞，但神经胶质修剪的细胞和分子基础尚不清楚。在这里，我们表明，果蝇幼虫的星形胶质细胞转化为吞噬细胞通过激活的细胞自主，类固醇依赖的程序在变态的开始，是主要的吞噬细胞类型的蛹neurophysium。我们研究了两个神经元群体的发育消除-蘑菇体（MB）γ神经元和vCrz+神经元（在腹神经索[VNC]中表达Corazonin [Crz]神经肽）-其中分别只有神经突被修剪或整个细胞被消除。我们发现MB γ轴突被星形胶质细胞以部分冗余的方式通过德雷珀和Crk/Mbc/dCed-12信号通路吞噬。相反，vCrz+细胞体的消除需要德雷珀，而vCrz+神经突的消除是由Crk/Mbc/dCed-12介导的，而不是德雷珀。有趣的是，我们还发现，消除德雷珀延迟vCrz+神经突变性，这表明胶质细胞通过吞噬信号促进神经突破坏。这项研究确定了一种新的作用，星形胶质细胞在突触和神经元碎片的清除和Crk/Mbc/dCed-12作为一种新的神经胶质细胞通路介导修剪和揭示，出乎意料的是，吞噬信号通路参与胶质细胞依赖于神经元碎片是否产生通过细胞死亡或局部修剪。
Neural circuit assembly involves an initial overproduction of neurons and synaptic connections, followed by their selective elimination. Tasdemir-Yilmaz and Freeman show that Drosophila larval astrocytes are the primary phagocytic cell type in the pupal CNS neuropil. MB γ neuron axons are engulfed by astrocytes using the Draper and Crk/Mbc/dCed-12 signaling pathways, while Crk/Mbc/dCed-12, but not Draper, mediates the elimination of vCrz+ neurites. Eliminating Draper signaling delays early vCrz+ neurite degeneration, suggesting that glial cells promote neurite destruction through engulfment signaling. Precise neural circuit assembly is achieved by initial overproduction of neurons and synapses, followed by refinement through elimination of exuberant neurons and synapses. Glial cells are the primary cells responsible for clearing neuronal debris, but the cellular and molecular basis of glial pruning is poorly defined. Here we show that Drosophila larval astrocytes transform into phagocytes through activation of a cell-autonomous, steroid-dependent program at the initiation of metamorphosis and are the primary phagocytic cell type in the pupal neuropil. We examined the developmental elimination of two neuron populations—mushroom body (MB) γ neurons and vCrz+ neurons (expressing Corazonin [Crz] neuropeptide in the ventral nerve cord [VNC])—where only neurites are pruned or entire cells are eliminated, respectively. We found that MB γ axons are engulfed by astrocytes using the Draper and Crk/Mbc/dCed-12 signaling pathways in a partially redundant manner. In contrast, while elimination of vCrz+ cell bodies requires Draper, elimination of vCrz+ neurites is mediated by Crk/Mbc/dCed-12 but not Draper. Intriguingly, we also found that elimination of Draper delayed vCrz+ neurite degeneration, suggesting that glia promote neurite destruction through engulfment signaling. This study identifies a novel role for astrocytes in the clearance of synaptic and neuronal debris and for Crk/Mbc/dCed-12 as a new glial pathway mediating pruning and reveals, unexpectedly, that the engulfment signaling pathways engaged by glia depend on whether neuronal debris was generated through cell death or local pruning.
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影响因子：
4.6
作者：
Cherbas, L;Hu, X;Cherbas, P
通讯作者：
Cherbas, P
影响因子：
64.5
作者：
KOELLE, MR;TALBOT, WS;HOGNESS, DS
通讯作者：
HOGNESS, DS
影响因子：
64.8
作者：
Hoeppner, DJ;Hengartner, MO;Schnabel, R
通讯作者：
Schnabel, R
影响因子：
16.2
作者：
Awasaki, T;Tatsumi, R;Ito, K
通讯作者：
Ito, K
DOI：
10.1523/jneurosci.5951-08.2009
发表时间：
2009-04-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Doherty J;Logan MA;Taşdemir OE;Freeman MR
通讯作者：
Freeman MR