The DLK signalling pathway--a double-edged sword in neural development and regeneration

EMBO Rep. 2013 Jul;14(7):605-14. doi: 10.1038/embor.2013.64. Epub 2013 May 17.


Dual leucine zipper kinase (DLK), a mitogen-activated protein kinase kinase kinase, controls axon growth, apoptosis and neuron degeneration during neural development, as well as neurodegeneration after various insults to the adult nervous system. Interestingly, recent studies have also highlighted a role of DLK in promoting axon regeneration in diverse model systems. Invertebrates and vertebrates, cold- and warm-blooded animals, as well as central and peripheral mammalian nervous systems all differ in their ability to regenerate injured axons. Here, we discuss how DLK-dependent signalling regulates apparently contradictory functions during neural development and regeneration in different species. In addition, we outline strategies to fine-tune DLK function, either alone or together with other approaches, to promote axon regeneration in the adult mammalian central nervous system.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Axons / metabolism*
  • Axons / pathology
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Central Nervous System / physiology*
  • Death-Associated Protein Kinases
  • Gene Expression Regulation, Developmental
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Neurogenesis / physiology*
  • Regeneration / physiology*
  • Signal Transduction / physiology*


  • Apoptosis Regulatory Proteins
  • Isoenzymes
  • Death-Associated Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases