Moving around in a worm: netrin UNC-6 and circumferential axon guidance in C. elegans

Trends Neurosci. 2002 Aug;25(8):423-9. doi: 10.1016/s0166-2236(02)02206-3.


How does an extracellular guidance molecule direct multiple growth cones to different positions? The answer is important for understanding the development of complex neural connections. UNC-6 is a member of the netrin family of guidance proteins. It has phylogenetically conserved domains that mediate its different guidance and branching activities. In the Caenorhabditis elegans embryo, UNC-6 is secreted ventrally and a pattern of circumferential axon tracts develops as pioneer growth cones bearing UNC-5 and UNC-40 receptors are directed towards, or away from, the ventral sources. Following the first migrations, UNC-6 from additional sources allows more complex migration patterns to emerge. In addition, at specific dorsoventral positions, locally restricted extracellular molecules alter growth cone responses to UNC-6, causing circumferentially migrating growth cones to turn and longitudinal nerves to develop. These observations show that extracellular guidance molecules can direct complex arrangements of migrating growth cones in vivo by eliciting different types of responses, by spatially and temporally regulating their expression and by working in concert with other extracellular molecules.

Publication types

  • Review

MeSH terms

  • Animals
  • Body Patterning / physiology
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins*
  • Cell Communication / physiology
  • Cell Differentiation / physiology*
  • Cell Movement / physiology*
  • Cues
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism*
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism*
  • Nerve Net / cytology
  • Nerve Net / embryology*
  • Nerve Net / metabolism
  • Nerve Tissue Proteins*
  • Nervous System / cytology
  • Nervous System / embryology*
  • Nervous System / metabolism
  • Netrin-1
  • Netrins
  • Signal Transduction / physiology
  • Tumor Suppressor Proteins


  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Netrins
  • Tumor Suppressor Proteins
  • UNC-6 protein, C elegans
  • Netrin-1