RRC ID 46517
著者 Teulière J, Gally C, Garriga G, Labouesse M, Georges-Labouesse E.
タイトル MIG-15 and ERM-1 promote growth cone directional migration in parallel to UNC-116 and WVE-1.
ジャーナル Development
Abstract 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.
巻・号 138(20)
ページ 4475-85
公開日 2011-10-1
DOI 10.1242/dev.061952
PII 138/20/4475
PMID 21937599
PMC PMC3177317
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cell Movement / physiology Cell Polarity Cytoskeletal Proteins / genetics Cytoskeletal Proteins / metabolism* Genes, Helminth Growth Cones / metabolism* Kinesins / genetics Kinesins / metabolism* Motor Neurons / metabolism Mutation Neurogenesis / genetics Neurogenesis / physiology RNA Interference
IF 5.611
引用数 15
WOS 分野 DEVELOPMENTAL BIOLOGY
リソース情報
線虫 tm677