MIG-10/lamellipodin and AGE-1/PI3K promote axon guidance and outgrowth in response to slit and netrin.
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.
Chang
Chieh
C
Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Adler
Carolyn E
CE
Krause
Matthias
M
Clark
Scott G
SG
Gertler
Frank B
FB
Tessier-Lavigne
Marc
M
Bargmann
Cornelia I
CI
D000818:Animals; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D006801:Humans; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009420:Nervous System / Q000254:growth & development; D000075385:Netrins; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011554:Pseudopodia / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; C105812:Mig-10 protein, C elegans; D009419:Nerve Tissue Proteins; D000075385:Netrins; C102174:UNC-40 protein, C elegans; C078146:UNC-6 protein, C elegans; C492285:slt-1 protein, C elegans; C511070:unc-34 protein, C elegans; D019869:Phosphatidylinositol 3-Kinases; C100662:AGE-1 protein, C elegans