Slit2-Mediated chemorepulsion and collapse of developing forebrain axons

Neuron. 1999 Mar;22(3):463-73. doi: 10.1016/s0896-6273(00)80702-3.

Abstract

Diffusible chemorepellents play a major role in guiding developing axons toward their correct targets by preventing them from entering or steering them away from certain regions. Genetic studies in Drosophila revealed a novel repulsive guidance system that prevents inappropriate axons from crossing the CNS midline; this repulsive system is mediated by the Roundabout (Robo) receptor and its secreted ligand Slit. In rodents, Robo and Slit are expressed in the spinal cord and Slit can repel spinal motor axons in vitro. Here, we extend these findings into higher brain centers by showing that Robo1 and Robo2, as well as Slit1 and Slit2, are often expressed in complementary patterns in the developing forebrain. Furthermore, we show that human Slit2 can repel olfactory and hippocampal axons and collapse their growth cones.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Axons / physiology*
  • Axons / ultrastructure
  • Cell Count
  • Cell Membrane / physiology
  • Cell Membrane / ultrastructure
  • Coculture Techniques
  • Culture Techniques
  • Drosophila
  • Drosophila Proteins*
  • Growth Cones / physiology
  • Growth Cones / ultrastructure
  • Hippocampus / cytology
  • Hippocampus / growth & development
  • Hippocampus / ultrastructure
  • Humans
  • In Situ Hybridization
  • Mice
  • Motor Neurons / physiology
  • Motor Neurons / ultrastructure
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / physiology*
  • Olfactory Bulb / cytology
  • Olfactory Bulb / growth & development
  • Olfactory Bulb / ultrastructure
  • Prosencephalon / cytology*
  • Prosencephalon / growth & development
  • Prosencephalon / ultrastructure
  • Rats
  • Rats, Wistar
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / physiology
  • Roundabout Proteins
  • Spinal Cord / cytology
  • Spinal Cord / growth & development
  • Spinal Cord / ultrastructure

Substances

  • Drosophila Proteins
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • sli protein, Drosophila