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

Abstract

A conditioning lesion of the peripheral sensory axon triggers robust central axon regeneration in mammals. We visualize the ASJ neuron of C. elegans with a cell-specific green fluorescent protein reporter driven by a thioredoxin trx-1 promoter and trigger conditioned regeneration by laser surgery or genetic disruption of sensory pathways. Utilizing calibrated fluorescent beads, we demonstrate that these neurons brighten when conditioned, suggesting that trx-1 expression indicates regenerative capacity. We show that trx-1 functionally enhances conditioned regeneration but inhibits non-conditioned regeneration. Finally, six strains isolated in a forward genetic screen for reduced fluorescence also show reduced axon outgrowth. We demonstrate a link between trx-1 expression and the conditioned state that we leverage to rapidly assess regenerative capacity.

High-throughput submicron-resolution microscopy of Caenorhabditis elegans populations under strong immobilization by cooling cultivation plates

“…Our laboratory studies neuroregeneration and, in a parallel study, identified that the expression of the gene, thioredoxin-1 (TXN/ trx-1 ), roughly correlates with regenerative capacity. 24 A fluorescent GFP reporter of trx-1 potentially allows high-throughput screening of regeneration genes without time-consuming surgery needed in previous studies. We are specifically interested in genes underlying lesion-conditioned regeneration, 25 which is distinct from other forms of neuronal regeneration mediated by the well-studied gene dual leucine zipper kinase DLK/ dlk-1 .…”