Developmental regulation of notochord-derived repulsion for dorsal root ganglion axons

Mol Cell Neurosci. 2004 Feb;25(2):217-27. doi: 10.1016/j.mcn.2003.10.005.

Abstract

During the initial stages of development, the notochord provides repulsive signals for dorsal root ganglion (DRG) axons via semaphorin 3A/neuropilin-1, axonin-1/SC2, and other unknown repulsive molecules. The notochord is known to produce aggrecan, one of the chondroitin sulfate proteoglycans (CSPGs). We report here that adding aggrecan to the culture medium cannot only induce DRG growth cone collapse, but also inhibit DRG axonal growth. Using cocultures composed of tissues derived from chick embryos or neuropilin-1-deficient mice treated with chondroitinase ABC, we show the direct evidence that CSPGs are involved in notochord-derived repulsion for DRG axons. At later developmental stages, CSPGs are involved in perinotochordal sheath-derived axon repulsion, but not in notochord core-derived repulsion. We further demonstrate that TAG-1/axonin-1/SC2 is not involved in mediating repulsive activities by CSPGs, but is required for notochord core-derived axon repulsion. Thus, notochord-derived multiple axon repulsions act in a spatiotemporal-specific manner to shape the initial trajectories of DRG axons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggrecans
  • Animals
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Communication / drug effects
  • Cell Communication / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Chick Embryo
  • Chondroitin ABC Lyase / pharmacology
  • Chondroitin Sulfate Proteoglycans / metabolism*
  • Coculture Techniques
  • Contactin 2
  • Extracellular Matrix Proteins*
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / embryology
  • Ganglia, Spinal / metabolism*
  • Gene Expression Regulation, Developmental / physiology*
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Lectins, C-Type
  • Mice
  • Mice, Knockout
  • Nerve Growth Factors / metabolism*
  • Neuropilin-1 / deficiency
  • Neuropilin-1 / genetics
  • Notochord / metabolism*
  • Organ Culture Techniques
  • Proteoglycans / metabolism
  • Proteoglycans / pharmacology

Substances

  • Acan protein, mouse
  • Aggrecans
  • Cell Adhesion Molecules, Neuronal
  • Chondroitin Sulfate Proteoglycans
  • Cntn2 protein, mouse
  • Contactin 2
  • Extracellular Matrix Proteins
  • Lectins, C-Type
  • Nerve Growth Factors
  • Proteoglycans
  • Neuropilin-1
  • Chondroitin ABC Lyase