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

Science. 2013 Apr 19;340(6130):372-376. doi: 10.1126/science.1231321.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Axons / physiology*
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microtubules / physiology
  • Nerve Regeneration / genetics
  • Nerve Regeneration / physiology*
  • Neurogenesis
  • Neurons / cytology
  • Neurons / physiology*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Transcription Factors / metabolism*

Substances

  • ALG-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • LIN-41 protein, C elegans
  • MicroRNAs
  • RNA-Binding Proteins
  • Transcription Factors
  • let-7 microRNA, C elegans