title: Dishevelled attenuates the repelling activity of Wnt signaling during neurite outgrowth in Caenorhabditis elegans.
abstract: Wnt proteins regulate axonal outgrowth along the anterior-posterior axis, but the intracellular mechanisms that modulate the strength of Wnt signaling in axon guidance are largely unknown. Using the Caenorhabditis elegans mechanosensory PLM neurons, we found that posteriorly enriched LIN-44/Wnt acts as a repellent to promote anteriorly directed neurite outgrowth through the LIN-17/Frizzled receptor, instead of controlling neuronal polarity as previously thought. Dishevelled (Dsh) proteins DSH-1 and MIG-5 redundantly mediate the repulsive activity of the Wnt signals to induce anterior outgrowth, whereas DSH-1 also provides feedback inhibition to attenuate the signaling to allow posterior outgrowth against the Wnt gradient. This inhibitory function of DSH-1, which requires its dishevelled, Egl-10, and pleckstrin (DEP) domain, acts by promoting LIN-17 phosphorylation and is antagonized by planar cell polarity signaling components Van Gogh (VANG-1) and Prickle (PRKL-1). Our results suggest that Dsh proteins both respond to Wnt signals to shape neuronal projections and moderate its activity to fine-tune neuronal morphology.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027.
authors.forename: Chaogu
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027.
authors.forename: Margarete
authors.initials: M
authors.lastname: Diaz-Cuadros
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027 mc21@columbia.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Chalfie
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D064113:CRISPR-Cas Systems; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D000072261:Dishevelled Proteins; D006023:Glycoproteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D016501:Neurites / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000502:physiology*; D019076:Transgenes / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; C569185:DSH-1 protein, C elegans; D000072261:Dishevelled Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; C095991:LIN-44 protein, C elegans
keywords: C. elegans; Wnt; axonal guidance; dishevelled; touch receptor neurons