Slit1 promotes regenerative neurite outgrowth of adult dorsal root ganglion neurons in vitro via binding to the Robo receptor

J Chem Neuroanat. 2010 Jul;39(4):256-61. doi: 10.1016/j.jchemneu.2010.02.001. Epub 2010 Feb 19.

Abstract

Secreted Slit proteins have previously been shown to signal through Roundabout (Robo) receptors to negatively regulate axon guidance and cell migration. During vertebrate development, Slit proteins have also been shown to stimulate branching and elongation of sensory axons and cortical dendrites. In this study, Slit1/Robo2 mRNA and protein expressions were detected in adult rat dorsal root ganglion (DRG) and in cultured DRG neurons. Treatment of both models with recombinant, soluble Slit1 protein was found to promote neurite outgrowth and elongation. In contrast, treatment with a recombinant human Robo2/Fc chimera inhibited neurite outgrowth and elongation. When adult DRG and cultured DRG neurons were pretreated with soluble recombinant human Robo2/Fc chimera, neurite outgrowth and elongation was not induced. These findings indicate that Slit1/Robo2 signaling may have a role in regulating peripheral nerve regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism*
  • Growth Cones / drug effects
  • Growth Cones / metabolism
  • Growth Cones / ultrastructure
  • Male
  • Nerve Regeneration / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / pharmacology
  • Neurites / drug effects
  • Neurites / metabolism*
  • Neurites / ultrastructure
  • Neurogenesis / physiology
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Immunologic / drug effects
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Recombinant Fusion Proteins
  • Sensory Receptor Cells / cytology
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / metabolism*

Substances

  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • Recombinant Fusion Proteins
  • Robo2 protein, rat
  • Slit1 protein, rat