MIG-10/lamellipodin and AGE-1/PI3K promote axon guidance and outgrowth in response to slit and netrin

Curr Biol. 2006 May 9;16(9):854-62. doi: 10.1016/j.cub.2006.03.083. Epub 2006 Apr 20.


Background: The cytoplasmic C. elegans protein MIG-10 affects cell migrations and is related to mammalian proteins that bind phospholipids and Ena/VASP actin regulators. In cultured cells, mammalian MIG-10 promotes lamellipodial growth and Ena/VASP proteins induce filopodia.

Results: We show here that during neuronal development, mig-10 and the C. elegans Ena/VASP homolog unc-34 cooperate to guide axons toward UNC-6 (netrin) and away from SLT-1 (Slit). The single mutants have relatively mild phenotypes, but mig-10; unc-34 double mutants arrest early in development with severe axon guidance defects. In axons that are guided toward ventral netrin, unc-34 is required for the formation of filopodia and mig-10 increases the number of filopodia. In unc-34 mutants, developing axons that lack filopodia are still guided to netrin through lamellipodial growth. In addition to its role in axon guidance, mig-10 stimulates netrin-dependent axon outgrowth in a process that requires the age-1 phosphoinositide-3 lipid kinase but not unc-34.

Conclusions: mig-10 and unc-34 organize intracellular responses to both attractive and repulsive axon guidance cues. mig-10 and age-1 lipid signaling promote axon outgrowth; unc-34 and to a lesser extent mig-10 promote filopodia formation. Surprisingly, filopodia are largely dispensable for accurate axon guidance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Axons / physiology*
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Adhesion Molecules / physiology
  • Cell Growth Processes / physiology
  • Humans
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Nervous System / growth & development
  • Netrins
  • Phosphatidylinositol 3-Kinases / physiology*
  • Pseudopodia / physiology


  • Caenorhabditis elegans Proteins
  • Cell Adhesion Molecules
  • Mig-10 protein, C elegans
  • Nerve Tissue Proteins
  • Netrins
  • UNC-40 protein, C elegans
  • UNC-6 protein, C elegans
  • slt-1 protein, C elegans
  • unc-34 protein, C elegans
  • Phosphatidylinositol 3-Kinases
  • AGE-1 protein, C elegans