Essential role of the apoptotic cell engulfment genes draper and ced-6 in programmed axon pruning during Drosophila metamorphosis
Essential role of the apoptotic cell engulfment genes draper and ced-6 in programmed axon pruning during Drosophila metamorphosis
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DOI：
10.1016/j.neuron.2006.04.027
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发表时间：
2006-06-15
期刊：
影响因子：
16.2
通讯作者：
Ito, K
中科院分区：
文献类型：
--
作者：
Awasaki, T;Tatsumi, R;Ito, K
轴突修剪是神经回路发育中的一种常见现象。以往的研究表明，在这一过程中，胶质细胞的吞噬作用是必不可少的。然而，其潜在的分子机制仍然未知。我们发现，德雷珀（drpr）和ced-6，这是必不可少的清除凋亡细胞在C。elegans，在果蝇变态期间幼虫轴突的胶质细胞吞噬中起作用。drpr突变和胶质细胞特异性敲低drpr和ced-6的RNA干扰抑制胶质细胞吞噬，导致轴突修剪的抑制。DRPR和CED-6在神经胶质作用中遗传地相互作用。微管细胞骨架的破坏轴突修剪发生通过蜕皮激素信号，独立的神经胶质细胞吞噬。这些发现表明胶质细胞通过drpr和ced-6吞噬变性轴突。我们认为凋亡细胞和变性轴突的活神经元被删除了类似的分子机制。
Axon pruning is a common phenomenon in neural circuit development. Previous studies demonstrate that the engulfing action of glial cells is essential in this process. The underlying molecular mechanisms, however, remain unknown. We show that draper(drpr) and ced-6, which are essential for the clearance of apoptotic cells in C. elegans, function in the glial engulfment of larval axons during Drosophila metamorphosis. The drpr mutation and glia-specific knockdown of drpr and ced-6 by RNA interference suppress glial engulfment, resulting in the inhibition of axon pruning. drpr and ced-6 interact genetically in the glial action. Disruption of the microtubule cytoskeleton in the axons to be pruned occurs via ecdysone signaling, independent of glial engulfment. These findings suggest that glial cells engulf degenerating axons through drpr and ced-6. We propose that apoptotic cells and degenerating axons of living neurons are removed by a similar molecular mechanism.