title: Netrin (UNC-6) mediates dendritic self-avoidance.
abstract: Dendrites from a single neuron may be highly branched but typically do not overlap. Self-avoidance behavior has been shown to depend on cell-specific membrane proteins that trigger mutual repulsion. Here we report the unexpected discovery that a diffusible cue, the axon guidance protein UNC-6 (Netrin), is required for self-avoidance of sister dendrites from the PVD nociceptive neuron in Caenorhabditis elegans. We used time-lapse imaging to show that dendrites fail to withdraw upon mutual contact in the absence of UNC-6 signaling. We propose a model in which the UNC-40 (Deleted in Colorectal Cancer; DCC) receptor captures UNC-6 at the tips of growing dendrites for interaction with UNC-5 on the apposing branch to induce mutual repulsion. UNC-40 also responds to dendritic contact through another pathway that is independent of UNC-6. Our findings offer a new model for how an evolutionarily conserved morphogenic cue and its cognate receptors can pattern a fundamental feature of dendritic architecture.
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Smith
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Watson
authors.forename: Miri K
authors.initials: MK
authors.lastname: VanHoven
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Colón-Ramos
authors.forename: David M
authors.initials: DM
authors.lastname: Miller
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D003712:Dendrites / Q000235:genetics / Q000502:physiology*; D006358:Hot Temperature; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000075385:Netrins; D009619:Nociceptors / Q000166:cytology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D059008:Time-Lapse Imaging
chemical_list: D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000075385:Netrins; C102174:UNC-40 protein, C elegans; C078146:UNC-6 protein, C elegans