MIG-10/Lamellipodin and AGE-1/PI3K Promote Axon Guidance and Outgrowth in Response to Slit and Netrin
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Gertler_MIG-10 Lamellipodin.pdf
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Author(s)
Chang, Chieh
Adler, Carolyn E.
Krause, Matthias
Clark, Scott G.
Tessier-Lavigne, Marc
Bargmann, Cornelia I.
Gertler, Frank
Date Issued
April 2006
Journal
Current Biology
Publisher
Elsevier
Citation
Chang, Chieh, Carolyn E. Adler, Matthias Krause, Scott G. Clark, Frank B. Gertler, Marc Tessier-Lavigne, and Cornelia I. Bargmann. “MIG-10/Lamellipodin and AGE-1/PI3K Promote Axon Guidance and Outgrowth in Response to Slit and Netrin.” Current Biology 16, no. 9 (May 2006): 854-862. Copyright © 2006 Elsevier Ltd.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1016/j.cub.2006.03.083
