The regeneration of an axon after injury is enhanced by prior `conditioning' lesions, which are thought to stimulate the expression of regeneration-associated genes (RAGs). Conditioning lesions have typically been introduced in vivo, but David Tonge and colleagues () now show that Xenopus dorsal root ganglia with attached peripheral nerves (PN-DRG) can be `conditioned' in vitro by a 3-day incubation in serum-free medium. The authors demonstrate that BDNF treatment stimulates axonal outgrowth in conditioned PN-DRG, even in the presence of the transcriptional inhibitor actinomycin D (which inhibits outgrowth in freshly dissected PN-DRG); thus, de novo mRNA synthesis occurs during in vitro conditioning, as it does in vivo. Moreover, inhibiting protein synthesis specifically in the distal nerve impairs the conditioning response, and the authors identify 32 proteins, including the oxidoreductase thioredoxin (Trx), that are synthesised and undergo retrograde transport during conditioning. Notably, inhibitors of Trx and Trx-specific morpholino oligonucleotides inhibit the conditioning response. Trx might, therefore, promote axonal regeneration, perhaps by upregulating RAGs.
