title: Target-derived GFRalpha1 as an attractive guidance signal for developing sensory and sympathetic axons via activation of Cdk5.
abstract: Immobilized and diffusible molecular cues regulate axon guidance during development. GFRalpha1, a GPI-anchored receptor for GDNF, is expressed as both membrane bound and secreted forms by accessory nerve cells and peripheral targets of developing sensory and sympathetic neurons during the period of target innervation. A relative deficit of GFRalpha1 in developing axons allows exogenous GFRalpha1 to capture GDNF and present it for recognition by axonal c-Ret receptors. Exogenous GFRalpha1 potentiates neurite outgrowth and acts as a long-range directional cue by creating positional information for c-Ret-expressing axons in the presence of a uniform concentration of GDNF. Soluble GFRalpha1 prolongs GDNF-mediated activation of cyclin-dependent kinase 5 (Cdk5), an event required for GFRalpha1-induced neurite outgrowth and axon guidance. Together with GDNF, target-derived GFRalpha1 can function in a non-cell-autonomous fashion as a chemoattractant cue with outgrowth promoting activity for peripheral neurons.
authors.affiliation: Division of Molecular Neurobiology, Department of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Ledda
authors.forename: Gustavo
authors.initials: G
authors.lastname: Paratcha
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Ibáñez
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D002642:Chick Embryo; D003463:Cues; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D005455:Fluorescent Antibody Technique; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D029721:Drosophila Proteins; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C495001:Ret protein, rat; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases