Awasaki Takeshi, Tatsumi Ryoko, Takahashi Kuniaki, Arai Kunizo, Nakanishi Yoshinobu, Ueda Ryu, Ito Kei
Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Neuron. 2006 Jun 15;50(6):855-67. doi: 10.1016/j.neuron.2006.04.027.
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.
轴突修剪是神经回路发育中的一种常见现象。先前的研究表明，胶质细胞的吞噬作用在这一过程中至关重要。然而，其潜在的分子机制仍然未知。我们发现，秀丽隐杆线虫中对凋亡细胞清除至关重要的draper（drpr）和ced-6，在果蝇变态发育期间幼虫轴突的胶质细胞吞噬过程中发挥作用。drpr突变以及通过RNA干扰对drpr和ced-6进行胶质细胞特异性敲低会抑制胶质细胞吞噬，从而导致轴突修剪受到抑制。drpr和ced-6在胶质细胞作用中存在遗传相互作用。待修剪轴突中的微管细胞骨架破坏是通过蜕皮激素信号传导发生的，与胶质细胞吞噬无关。这些发现表明，胶质细胞通过drpr和ced-6吞噬退化的轴突。我们提出，凋亡细胞和活神经元的退化轴突通过类似的分子机制被清除。
