Developmental decline in neuronal regeneration by the progressive change of two intrinsic timers
Program in Molecular Medicine; RNA Therapeutics Institute
Aging; Animals; Axons; Caenorhabditis elegans; Caenorhabditis elegans Proteins; MicroRNAs; Microtubules; Nerve Regeneration; Neurogenesis; Neurons; RNA-Binding Proteins; Transcription Factors
Biochemistry | Developmental Biology | Developmental Neuroscience | Molecular Biology | Molecular Genetics
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
Science. 2013 Apr 19;340(6130):372-6. doi: 10.1126/science.1231321. Link to article on publisher's site
Science (New York, N.Y.)
Zou, Yan; Chiu, Hui; Zinovyeva, Anna Y.; Ambros, Victor R.; Chuang, Chiou-Fen; and Chang, Chieh, "Developmental decline in neuronal regeneration by the progressive change of two intrinsic timers" (2013). Program in Molecular Medicine Publications and Presentations. 25.