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

Author:

Grooms Noa W.F.1ORCID,Fitzgerald Michael Q.1ORCID,Zuckerman Binyamin2ORCID,Ureña Samuel E.1,Weinberger Leor S.2ORCID,Chung Samuel H.1ORCID

Affiliation:

1. Department of Bioengineering Northeastern University Boston Massachusetts USA

2. Gladstone/UCSF Center for Cell Circuitry Gladstone Institutes San Francisco California USA

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.

Funder

Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases

European Molecular Biology Organization

Morton Cure Paralysis Fund

National Institute of Neurological Disorders and Stroke

Publisher

Wiley

Subject

Cell Biology,Genetics,Molecular Biology,Biochemistry,Structural Biology,Biophysics

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