期刊
SCIENCE
卷 340, 期 6130, 页码 372-376出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1231321
关键词
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资金
- Whitehall Foundation
- March of Dimes Foundation
- Canada Foundation for Innovation
- Alfred P. Sloan Research Fellowships
- NIH [R01 GM098026, R01 GM034028-25]
Like mammalian neurons, Caenorhabditis elegans neurons lose axon regeneration ability as they age, but it is not known why. Here, we report that let-7 contributes to a developmental decline in anterior ventral microtubule (AVM) axon regeneration. In older AVM axons, let-7 inhibits regeneration by down-regulating LIN-41, an important AVM axon regeneration-promoting factor. Whereas let-7 inhibits lin-41 expression in older neurons through the lin-41 3' untranslated region, lin-41 inhibits let-7 expression in younger neurons through Argonaute ALG-1. This reciprocal inhibition ensures that axon regeneration is inhibited only in older neurons. These findings show that a let-7-lin-41 regulatory circuit, which was previously shown to control timing of events in mitotic stem cell lineages, is reutilized in postmitotic neurons to control postdifferentiation events.
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