DLK regulates distinctive transcriptional regeneration program after peripheral nerve injury

The dual leucine zipper kinase (DLK) is a mitogen-activated kinase kinase kinase that can activate the downstream cJun N terminal kinase (JNK) pathway (ref). We have previously reported that DLK is a positive regulator of the retrograde injury signaling and axon regeneration that unfolds after sciatic nerve injury (ref). Since DLK is required for activities of injury-associated transcription factors such as cJun and STAT3, we hypothesized that DLK is also necessary for the transcriptional responses to peripheral nerve injury. In the current study, we identify DLK-dependent transcriptome in dorsal root ganglion (DRG) neurons using a sciatic nerve injury paradigm. The DEG analysis reveals that DLK regulates regeneration/injury-associated genes in both basal and injured conditions. By performing gene ontology analysis, we suggest functional annotations and the involved genes as regulatory components of the axonal regeneration program. Finally, our comparative analysis indicates that DLK is required for a specific retrograde signaling pathway that regulates a regeneration program shared between PNS and CNS models.

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