Document Detail

MIG-15 and ERM-1 promote growth cone directional migration in parallel to UNC-116 and WVE-1.
MedLine Citation:
PMID:  21937599     Owner:  NLM     Status:  MEDLINE    
Neurons require precise targeting of their axons to form a connected network and a functional nervous system. Although many guidance receptors have been identified, much less is known about how these receptors signal to direct growth cone migration. We used Caenorhabditis elegans motoneurons to study growth cone directional migration in response to a repellent UNC-6 (netrin homolog) guidance cue. The evolutionarily conserved kinase MIG-15 [homolog of Nck-interacting kinase (NIK)] regulates motoneuron UNC-6-dependent repulsion through unknown mechanisms. Using genetics and live imaging techniques, we show that motoneuron commissural axon morphology defects in mig-15 mutants result from impaired growth cone motility and subsequent failure to migrate across longitudinal obstacles or retract extra processes. To identify new genes acting with mig-15, we screened for genetic enhancers of the mig-15 commissural phenotype and identified the ezrin/radixin/moesin ortholog ERM-1, the kinesin-1 motor UNC-116 and the actin regulator WVE-1 complex. Genetic analysis indicates that mig-15 and erm-1 act in the same genetic pathway to regulate growth cone migration and that this pathway functions in parallel to the UNC-116/WVE-1 pathway. Further, time-lapse imaging of growth cones in mutants suggests that UNC-116 might be required to stimulate protrusive activity at the leading edge, whereas MIG-15 and ERM-1 maintain low activity at the rear edge. Together, these results support a model in which the MIG-15 kinase and the UNC-116-WVE-1 complex act on opposite sides of the growth cone to promote robust directional migration.
Jérôme Teulière; Christelle Gally; Gian Garriga; Michel Labouesse; Elisabeth Georges-Labouesse
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  138     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-22     Completed Date:  2011-11-28     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  4475-85     Citation Subset:  IM    
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MeSH Terms
Caenorhabditis elegans / genetics,  growth & development*,  metabolism*
Caenorhabditis elegans Proteins / genetics,  metabolism*
Cell Cycle Proteins / genetics,  metabolism*
Cell Movement / physiology
Cell Polarity
Cytoskeletal Proteins / genetics,  metabolism*
Genes, Helminth
Growth Cones / metabolism*
Kinesin / genetics,  metabolism*
Motor Neurons / metabolism
Neurogenesis / genetics,  physiology
RNA Interference
Grant Support
Reg. No./Substance:
0/Caenorhabditis elegans Proteins; 0/Cell Cycle Proteins; 0/Cytoskeletal Proteins; 0/ERM-1 protein, C elegans; 0/UNC-116 protein, C elegans; 0/wve-1 protein, C elegans; EC 3.6.1.-/Kinesin

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