Expression of thioredoxin-1 in the ASJ neuron corresponds with and enhances intrinsic regenerative capacity under lesion conditioning in C. elegans

FEBS Lett. 2023 Jul;597(14):1880-1893. doi: 10.1002/1873-3468.14684. Epub 2023 Jun 19.

Abstract

A conditioning lesion of the peripheral sensory axon triggers robust central axon regeneration in mammals. We trigger conditioned regeneration in the Caenorhabditis elegans ASJ neuron by laser surgery or genetic disruption of sensory pathways. Conditioning upregulates thioredoxin-1 (trx-1) expression, as indicated by trx-1 promoter-driven expression of green fluorescent protein and fluorescence in situ hybridization (FISH), suggesting trx-1 levels and associated fluorescence indicate regenerative capacity. The redox activity of trx-1 functionally enhances conditioned regeneration, but both redox-dependent and -independent activity inhibit non-conditioned regeneration. Six strains isolated in a forward genetic screen for reduced fluorescence, which suggests diminished regenerative potential, also show reduced axon outgrowth. We demonstrate an association between trx-1 expression and the conditioned state that we leverage to rapidly assess regenerative capacity.

Keywords: C. elegans; fluorescence microscopy; genetic screen; lesion conditioning; neuron regeneration; redox biology; thioredoxin.

Publication types

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

MeSH terms

  • Animals
  • Axons / metabolism
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / metabolism
  • In Situ Hybridization, Fluorescence
  • Mammals / genetics
  • Mammals / metabolism
  • Nerve Regeneration / genetics
  • Neurons / metabolism
  • Thioredoxins / genetics
  • Thioredoxins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Thioredoxins