The divergent Robo family protein rig-1/Robo3 is a negative regulator of slit responsiveness required for midline crossing by commissural axons

Cell. 2004 Apr 16;117(2):157-69. doi: 10.1016/s0092-8674(04)00303-4.

Abstract

Commissural axons in vertebrates and insects are initially attracted to the nervous system midline, but once they reach this intermediate target they undergo a dramatic switch, becoming responsive to repellent Slit proteins at the midline, which expel them onto the next leg of their trajectory. We have unexpectedly implicated a divergent member of the Robo family, Rig-1 (or Robo3), in preventing premature Slit sensitivity in mammals. Expression of Rig-1 protein by commissural axons is inversely correlated with Slit sensitivity. Removal of Rig-1 results in a total failure of commissural axons to cross. Genetic and in vitro analyses indicate that Rig-1 functions to repress Slit responsiveness similarly to Commissureless (Comm) in Drosophila. Unlike Comm, however, Rig-1 does not produce its effect by downregulating Robo receptors on precrossing commissural axon membranes. These results identify a mechanism for regulating Slit repulsion that helps choreograph the precise switch from attraction to repulsion at a key intermediate axonal target.

Publication types

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

MeSH terms

  • Animals
  • COS Cells
  • Cell Communication / genetics
  • Cell Differentiation / genetics*
  • Cues
  • Drosophila Proteins*
  • Fetus
  • Functional Laterality / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Nervous System Malformations / genetics*
  • Nervous System Malformations / pathology
  • Rats
  • Receptors, Immunologic / deficiency*
  • Receptors, Immunologic / genetics
  • Spinal Cord / abnormalities*
  • Spinal Cord / metabolism
  • Spinal Cord / pathology

Substances

  • Drosophila Proteins
  • Glycoproteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • Robo3 protein, mouse
  • comm protein, Drosophila
  • slit protein, vertebrate