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 journalArticle

4 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 1

Fingerprint

Leucine Zippers
Peripheral Nerve Injuries
Regeneration
Phosphotransferases
Wounds and Injuries
Axons
Karyopherins
Gene Ontology
Ion Transport
Sensory Receptor Cells
Sciatic Nerve
Transcriptome
Knockout Mice
Genes
Apoptosis
Gene Expression

Keywords

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

ASJC Scopus subject areas

  • Neurology

Cite this

DLK regulates a distinctive transcriptional regeneration program after peripheral nerve injury. / Shin, Jung Eun; Ha, Hongseok; Kim, Yoon Ki; Cho, Yongcheol; DiAntonio, Aaron.

In: Neurobiology of Disease, Vol. 127, 01.07.2019, p. 178-192.

Research output: Contribution to journalArticle

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