The divergent Robo family protein rig-1/Robo3 is a negative regulator of slit responsiveness required for midline crossing by commissural axons.
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.
Sabatier
Christelle
C
Howard Hughes Medical Institute, Department of Anatomy and Department of Biochemistry and Biophysics, The University of California, San Francisco, San Francisco, CA 94143, USA.
Plump
Andrew S
AS
Le Ma
Brose
Katja
K
Tamada
Atsushi
A
Murakami
Fujio
F
Lee
Eva Y-H P
EY
Tessier-Lavigne
Marc
M
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
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