Hoopfer Eric D, McLaughlin Todd, Watts Ryan J, Schuldiner Oren, O'Leary Dennis D M, Luo Liqun
Howard Hughes Medical Institute, Department of Biological Sciences and Neurosciences Program, Stanford University, 385 Serra Mall, Stanford, California 94305, USA.
Neuron. 2006 Jun 15;50(6):883-95. doi: 10.1016/j.neuron.2006.05.013.
Axon pruning by degeneration remodels exuberant axonal connections and is widely required for the development of proper circuitry in the nervous system from insects to mammals. Developmental axon degeneration morphologically resembles injury-induced Wallerian degeneration, suggesting similar underlying mechanisms. As previously reported for mice, we show that Wlds protein substantially delays Wallerian degeneration in flies. Surprisingly, Wlds has no effect on naturally occurring developmental axon degeneration in flies or mice, although it protects against injury-induced degeneration of the same axons at the same developmental age. By contrast, the ubiquitin-proteasome system is intrinsically required for both developmental and injury-induced axon degeneration. We also show that the glial cell surface receptor Draper is required for efficient clearance of axon fragments during developmental axon degeneration, similar to its function in injury-induced degeneration. Thus, mechanistically, naturally occurring developmental axon pruning by degeneration and injury-induced axon degeneration differ significantly in early steps, but may converge onto a common execution pathway.
通过退化进行的轴突修剪重塑了过度生长的轴突连接，并且从昆虫到哺乳动物，神经系统中适当神经回路的发育广泛需要这一过程。发育性轴突退化在形态上类似于损伤诱导的华勒氏变性，提示存在相似的潜在机制。正如之前对小鼠的报道，我们发现Wlds蛋白可显著延缓果蝇的华勒氏变性。令人惊讶的是，Wlds对果蝇或小鼠中自然发生的发育性轴突退化没有影响，尽管它能保护相同发育阶段的相同轴突免受损伤诱导的退化。相比之下，泛素-蛋白酶体系统对于发育性和损伤诱导的轴突退化都是内在必需的。我们还表明，胶质细胞表面受体Draper在发育性轴突退化过程中对轴突片段的有效清除是必需的，这与其在损伤诱导的退化中的功能类似。因此，从机制上讲，自然发生的通过退化进行的发育性轴突修剪和损伤诱导的轴突退化在早期步骤上有显著差异，但可能会汇聚到一个共同的执行途径。
