Shared receptors in axon guidance: SAX-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function

Nat Neurosci. 2002 Nov;5(11):1147-54. doi: 10.1038/nn956.


The C. elegans SAX-3/Robo receptor acts in anterior-posterior, dorsal-ventral and midline guidance decisions. Here we show that SAX-3 signaling involves the C. elegans Enabled protein UNC-34 and an unexpected Netrin-independent function of the Netrin receptor UNC-40/DCC. Genetic interactions with gain- and loss-of-function mutations suggest that unc-34 and unc-40 act together with sax-3 in several guidance decisions, but the C. elegans Netrin gene unc-6 does not act in the same genetic pathways. Within the migrating axon, sax-3, unc-34 and unc-40 all act cell-autonomously. Our results support a role for UNC-34/Enabled proteins in SAX-3-mediated repulsion, and show that UNC-40/DCC can potentiate SAX-3/Robo signaling via a mechanism that may involve direct binding of the two guidance receptors. A combinatorial logic dictates alternative functions for UNC-40/DCC, which can act in attraction to UNC-6/Netrin, repulsion from Netrin (with UNC-5), or repulsion from Slit (with SAX-3).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Axons / physiology*
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Developmental
  • Growth Cones / physiology
  • Helminth Proteins / metabolism
  • Mutation / physiology
  • Nerve Tissue Proteins*
  • Netrins
  • Phenotype
  • Receptors, Cell Surface / metabolism
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Signal Transduction / genetics


  • Caenorhabditis elegans Proteins
  • Cell Adhesion Molecules
  • DNA-Binding Proteins
  • ENA-VASP proteins
  • Helminth Proteins
  • Nerve Tissue Proteins
  • Netrins
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • UNC-40 protein, C elegans
  • UNC-6 protein, C elegans
  • roundabout protein
  • UNC-5 protein, C elegans