Netrin (UNC-6) mediates dendritic self-avoidance

Nat Neurosci. 2012 Mar 18;15(5):731-7. doi: 10.1038/nn.3065.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Cloning, Molecular
  • Dendrites / genetics
  • Dendrites / physiology*
  • Hot Temperature
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microscopy, Confocal
  • Models, Molecular
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Netrins
  • Nociceptors / cytology*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Time Factors
  • Time-Lapse Imaging

Substances

  • Caenorhabditis elegans Proteins
  • Cell Adhesion Molecules
  • Luminescent Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Netrins
  • UNC-40 protein, C elegans
  • UNC-6 protein, C elegans