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Article
Developmental decline in neuronal regeneration by the progressive change of two intrinsic timers
Program in Molecular Medicine Publications and Presentations
  • Yan Zou, Cincinnati Children's Hospital Research Foundation
  • Hui Chiu, Cincinnati Children's Hospital Research Foundation
  • Anna Y. Zinovyeva, University of Massachusetts Medical School Worcester
  • Victor R. Ambros, University of Massachusetts Medical School
  • Chiou-Fen Chuang, Cincinnati Children's Hospital Research Foundation
  • Chieh Chang, Cincinnati Children's Hospital Research Foundation
UMMS Affiliation
Program in Molecular Medicine; RNA Therapeutics Institute
Date
4-19-2013
Document Type
Article
Medical Subject Headings
Aging; Animals; Axons; Caenorhabditis elegans; Caenorhabditis elegans Proteins; MicroRNAs; Microtubules; Nerve Regeneration; Neurogenesis; Neurons; RNA-Binding Proteins; Transcription Factors
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.
Comments

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

Related Resources
Link to Article in PubMed
PubMed ID
23599497
Citation Information
Yan Zou, Hui Chiu, Anna Y. Zinovyeva, Victor R. Ambros, et al.. "Developmental decline in neuronal regeneration by the progressive change of two intrinsic timers" Vol. 340 Iss. 6130 (2013) ISSN: 0036-8075 (Linking)
Available at: http://works.bepress.com/victor_ambros/29/