Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling

Science. 2003 Dec 12;302(5652):1984-8. doi: 10.1126/science.1089610.

Abstract

Commissural neurons in the mammalian dorsal spinal cord send axons ventrally toward the floor plate, where they cross the midline and turn anteriorly toward the brain; a gradient of chemoattractant(s) inside the spinal cord controls this turning. In rodents, several Wnt proteins stimulate the extension of commissural axons after midline crossing (postcrossing). We found that Wnt4 messenger RNA is expressed in a decreasing anterior-to-posterior gradient in the floor plate, and that a directed source of Wnt4 protein attracted postcrossing commissural axons. Commissural axons in mice lacking the Wnt receptor Frizzled3 displayed anterior-posterior guidance defects after midline crossing. Thus, Wnt-Frizzled signaling guides commissural axons along the anterior-posterior axis of the spinal cord.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Axons / ultrastructure
  • Brain / embryology
  • Brain / metabolism
  • COS Cells
  • Central Nervous System / cytology
  • Central Nervous System / embryology*
  • Central Nervous System / metabolism
  • Cues
  • Culture Techniques
  • Diffusion
  • Frizzled Receptors
  • Gene Expression Profiling
  • Growth Cones / physiology
  • Growth Cones / ultrastructure
  • In Situ Hybridization
  • Membrane Proteins*
  • Mice
  • Mice, Knockout
  • Neurons / physiology*
  • Proteins / pharmacology
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction*
  • Spinal Cord / cytology*
  • Spinal Cord / embryology
  • Spinal Cord / metabolism
  • Transfection
  • Wnt Proteins
  • Wnt4 Protein

Substances

  • Frizzled Receptors
  • Fzd3 protein, mouse
  • Membrane Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • Sfrp2 protein, mouse
  • Wnt Proteins
  • Wnt4 Protein
  • Wnt4 protein, mouse