title: The divergent Robo family protein rig-1/Robo3 is a negative regulator of slit responsiveness required for midline crossing by commissural axons.
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.
authors.affiliation: Howard Hughes Medical Institute, Department of Anatomy and Department of Biochemistry and Biophysics, The University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Christelle
authors.initials: C
authors.lastname: Sabatier
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Plump
authors.lastname: Le Ma
authors.forename: Katja
authors.initials: K
authors.lastname: Brose
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tamada
authors.forename: Fujio
authors.initials: F
authors.lastname: Murakami
authors.forename: Eva Y-H P
authors.initials: EY
authors.lastname: Lee
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
mesh_terms: D000818:Animals; D019556:COS Cells; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D003463:Cues; D029721:Drosophila Proteins; D005333:Fetus; D007839:Functional Laterality / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009421:Nervous System Malformations / Q000235:genetics* / Q000473:pathology; D051381:Rats; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000172:deficiency* / Q000235:genetics; D013116:Spinal Cord / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D000097905:Roundabout Proteins
chemical_list: D029721:Drosophila Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins; C110665:comm protein, Drosophila; C120566:slit protein, vertebrate