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

Cell | Apr 16, 2004

http://www.ncbi.nlm.nih.gov/pubmed/15084255

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.

Pubmed ID: 15084255 RIS Download

Mesh terms: Animals | COS Cells | Cell Communication | Cell Differentiation | Cues | Drosophila Proteins | Fetus | Functional Laterality | Gene Expression Regulation, Developmental | Glycoproteins | Growth Cones | Membrane Proteins | Mice | Mice, Knockout | Mutation | Nerve Tissue Proteins | Nervous System Malformations | Rats | Receptors, Immunologic | Spinal Cord

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Mouse Genome Informatics (Data, Gene Annotation)

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