DLK regulates a distinctive transcriptional regeneration program after peripheral nerve injury

Jung Eun Shin, Hongseok Ha, Yoon Ki Kim, Yongcheol Cho, Aaron DiAntonio

    Research output: Contribution to journalArticlepeer-review

    45 Citations (Scopus)

    Abstract

    Following damage to a peripheral nerve, injury signaling pathways converge in the cell body to generate transcriptional changes that support axon regeneration. Here, we demonstrate that dual leucine zipper kinase (DLK), a central regulator of injury responses including axon regeneration and neuronal apoptosis, is required for the induction of the pro-regenerative transcriptional program in response to peripheral nerve injury. Using a sensory neuron-conditional DLK knockout mouse model, we show a time course for the dependency of gene expression changes on the DLK pathway after sciatic nerve injury. Gene ontology analysis reveals that DLK-dependent gene sets are enriched for specific functional annotations such as ion transport and immune response. A series of comparative analyses shows that the DLK-dependent transcriptional program is distinct from that promoted by the importin-dependent retrograde signaling pathway, while it is partially shared between PNS and CNS injury responses. We suggest that DLK-dependency might provide a selective filter for regeneration-associated genes among the injury-responsive transcriptome.

    Original languageEnglish
    Pages (from-to)178-192
    Number of pages15
    JournalNeurobiology of Disease
    Volume127
    DOIs
    Publication statusPublished - 2019 Jul

    Bibliographical note

    Publisher Copyright:
    © 2019 Elsevier Inc.

    Keywords

    • Axon regeneration
    • Conditioning injury
    • Dual leucine zipper kinase
    • Neurodegeneration
    • Neuroinflammation
    • Pain

    ASJC Scopus subject areas

    • Neurology

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