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