Transcriptional Control of Peripheral Nerve Regeneration

Transcription factors are master regulators of various cellular processes under diverse physiological and pathological conditions. Many transcription factors that are differentially expressed after injury to peripheral nerves play important roles in nerve regeneration. Considering that rapid and timely regrowth of injured axons is a prerequisite for successful target reinnervation, here, we compile transcription factors that mediates axon elongation, including axon growth suppressor Klf4 and axon growth promoters c-Myc, Sox11, STAT3, Atf3, c-Jun, Smad1, C/EBPδ, and p53. Besides neuronal changes, Schwann cell phenotype modulation is also critical for nerve regeneration. The activation of Schwann cells at early time points post injury provides a permissive microenvironment whereas the re-differentiation of Schwann cells at later time points supports myelin sheath formation. Hence, c-Jun and Sox2, two critical drivers for Schwann cell reprogramming, as well as Krox-20 and Sox10, two essential regulators of Schwann cell myelination, are reviewed. These transcription factors may serve as promising targets for promoting the functional recovery of injured peripheral nerves.