Developmental decline in neuronal regeneration by the progressive change of two intrinsic timersProgram in Molecular Medicine Publications and Presentations
UMMS AffiliationProgram in Molecular Medicine; RNA Therapeutics Institute
Medical Subject HeadingsAging; Animals; Axons; Caenorhabditis elegans; Caenorhabditis elegans Proteins; MicroRNAs; Microtubules; Nerve Regeneration; Neurogenesis; Neurons; RNA-Binding Proteins; Transcription Factors
AbstractLike 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.
Related ResourcesLink to Article in PubMed
Citation InformationYan 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/