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Science. 2013 Apr 19;340(6130):372-376. doi: 10.1126/science.1231321.

Developmental decline in neuronal regeneration by the progressive change of two intrinsic timers.

Author information

1
Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio 45229.
2
RNA Therapeutics Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
3
Dept. of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 1B1, Canada.
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Contributed equally

Abstract

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.

PMID:
23599497
PMCID:
PMC4074024
DOI:
10.1126/science.1231321
[Indexed for MEDLINE]
Free PMC Article

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