The growth factor SVH-1 regulates axon regeneration in C. elegans via the JNK MAPK cascade

Nat Neurosci. 2012 Mar 4;15(4):551-7. doi: 10.1038/nn.3052.


The ability of neurons to undergo regenerative growth after injury is governed by cell-intrinsic and cell-extrinsic regeneration pathways. These pathways represent potential targets for therapies to enhance regeneration. However, the signaling pathways that orchestrate axon regeneration are not well understood. In Caenorhabditis elegans, the Jun N-terminal kinase (JNK) and p38 MAP kinase (MAPK) pathways are important for axon regeneration. We found that the C. elegans SVH-1 growth factor and its receptor, SVH-2 tyrosine kinase, regulate axon regeneration. Loss of SVH-1-SVH-2 signaling resulted in a substantial defect in the ability of neurons to regenerate, whereas its activation improved regeneration. Furthermore, SVH-1-SVH-2 signaling was initiated extrinsically by a pair of sensory neurons and functioned upstream of the JNK-MAPK pathway. Thus, SVH-1-SVH-2 signaling via activation of the MAPK pathway acts to coordinate neuron regeneration response after axon injury.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Axons / enzymology
  • Axons / physiology*
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / physiology*
  • Intercellular Signaling Peptides and Proteins / physiology*
  • JNK Mitogen-Activated Protein Kinases / physiology
  • MAP Kinase Signaling System / physiology*
  • Molecular Sequence Data
  • Nerve Regeneration / physiology*


  • Caenorhabditis elegans Proteins
  • Intercellular Signaling Peptides and Proteins
  • SVH-1 protein, C elegans
  • JNK Mitogen-Activated Protein Kinases

Associated data

  • GENBANK/AB693146
  • GENBANK/AB693147