DLK regulates a distinctive transcriptional regeneration program after peripheral nerve injury.
Neurobiol Dis
; 127: 178-192, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-30735704
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nervo Isquiático
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Transdução de Sinais
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MAP Quinase Quinase Quinases
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Traumatismos dos Nervos Periféricos
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Regeneração Nervosa
Limite:
Animals
Idioma:
En
Revista:
Neurobiol Dis
Ano de publicação:
2019
Tipo de documento:
Article