title: Developmental decline in neuronal regeneration by the progressive change of two intrinsic timers.
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.
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio 45229.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio 45229.
authors.forename: Hui
authors.initials: H
authors.lastname: Chiu
authors.affiliation: RNA Therapeutics Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
authors.forename: Anna
authors.initials: A
authors.lastname: Zinovyeva
authors.affiliation: RNA Therapeutics Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
authors.forename: Victor
authors.initials: V
authors.lastname: Ambros
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio 45229.
authors.forename: Chiou-Fen
authors.initials: CF
authors.lastname: Chuang
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio 45229.|Dept. of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 1B1, Canada.
authors.forename: Chieh
authors.initials: C
authors.lastname: Chang
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000254:growth & development* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000502:physiology; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C558782:ALG-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C410586:LIN-41 protein, C elegans; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C474488:let-7 microRNA, C elegans