Title

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

UMMS Affiliation

Program in Molecular Medicine; RNA Therapeutics Institute

Publication Date

4-19-2013

Document Type

Article

Subjects

Aging; Animals; Axons; Caenorhabditis elegans; Caenorhabditis elegans Proteins; MicroRNAs; Microtubules; Nerve Regeneration; Neurogenesis; Neurons; RNA-Binding Proteins; Transcription Factors

Disciplines

Biochemistry | Developmental Biology | Developmental Neuroscience | Molecular Biology | Molecular Genetics

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.

DOI of Published Version

10.1126/science.1231321

Source

Science. 2013 Apr 19;340(6130):372-6. doi: 10.1126/science.1231321. Link to article on publisher's site

Journal/Book/Conference Title

Science (New York, N.Y.)

Related Resources

Link to Article in PubMed

PubMed ID

23599497

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