title: VANG-1 and PRKL-1 cooperate to negatively regulate neurite formation in Caenorhabditis elegans.
abstract: Neuritogenesis is a critical early step in the development and maturation of neurons and neuronal circuits. While extracellular directional cues are known to specify the site and orientation of nascent neurite formation in vivo, little is known about the genetic pathways that block inappropriate neurite emergence in order to maintain proper neuronal polarity. Here we report that the Caenorhabditis elegans orthologues of Van Gogh (vang-1), Prickle (prkl-1), and Dishevelled (dsh-1), core components of planar cell polarity (PCP) signaling, are required in a subset of peripheral motor neurons to restrict neurite emergence to a specific organ axis. In loss-of-function mutants, neurons display supernumerary neurites that extend inappropriately along the orthogonal anteroposterior (A/P) body axis. We show that autonomous and non-autonomous gene activities are required early and persistently to inhibit the formation or consolidation of growth cone protrusions directed away from organ precursor cells. Furthermore, prkl-1 overexpression is sufficient to suppress neurite formation and reorient neuronal polarity in a vang-1- and dsh-1-dependent manner. Our findings suggest a novel role for a PCP-like pathway in maintaining polarized neuronal morphology by inhibiting neuronal responses to extrinsic or intrinsic cues that would otherwise promote extraneous neurite formation.
authors.affiliation: Ottawa Hospital Research Institute, Neuroscience Program, Heart and Stroke Foundation Centre for Stroke Recovery, University of Ottawa, Ottawa, Canada.
authors.forename: Leticia
authors.initials: L
authors.lastname: Sanchez-Alvarez
authors.forename: Jiravat
authors.initials: J
authors.lastname: Visanuvimol
authors.forename: Andrea
authors.initials: A
authors.lastname: McEwan
authors.forename: Anna
authors.initials: A
authors.lastname: Su
authors.forename: Janice H
authors.initials: JH
authors.lastname: Imai
authors.forename: Antonio
authors.initials: A
authors.lastname: Colavita
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity / Q000235:genetics*; D000072261:Dishevelled Proteins; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; C569185:DSH-1 protein, C elegans; D000072261:Dishevelled Proteins; D047908:Intracellular Signaling Peptides and Proteins; C569184:PRKL-1 protein, C elegans; D010750:Phosphoproteins; C549532:Vang-1 protein, C elegans