Activation of taf7l promotes sensory nerve regeneration by enhancing conditioning effect

Peripheral nervous system (PNS) neurons can regenerate after injury, yet functional recovery is often limited, especially following proximal lesions or delayed repair. Preconditioning nerve injury accelerates axonal growth by inducing regeneration associated genes (RAGs). To identify novel growth regulators, we screened nine genetically diverse Collaborative Cross (CC) mouse strains for strain-dependent differences in dorsal root ganglion (DRG) neurite outgrowth on Matrigel. All strains exhibited a ≥ 2-fold preconditioning effect, with DBA/2J showing the most pronounced growth. Genome-wide expression profiling revealed Taf7l as the transcript most strongly correlated with neurite outgrowth. Immunohistochemistry demonstrated Taf7l localization in DRG neurons, with expression enhanced after preconditioning. Quantitative RT-PCR showed a progressive post-injury increase in Taf7l mRNA, reaching > 5-fold by day 14. Functional studies using lentiviral vectors showed that Taf7l knockdown reduced neurite length by 27% without affecting initiation rate, while Taf7l overexpression significantly increased both initiation rate and axonal length. These findings identify Taf7l, previously known for roles in spermatogenesis and adipogenesis, as a novel transcriptional regulator in neurons. Taf7l is induced by nerve injury and modulates neurite outgrowth, suggesting it as a potential therapeutic target to enhance PNS regenerative capacity.