title: Slit/Robo-mediated chemorepulsion of vagal sensory axons in the fetal gut.
abstract: BACKGROUND
  The vagus nerve descends from the brain to the gut during fetal life to reach specific targets in the bowel wall. Vagal sensory axons have been shown to respond to the axon guidance molecule netrin and to its receptor, deleted in colorectal cancer (DCC). As there are regions of the gut wall into which vagal axons do and do not extend, it is likely that a combination of attractive and repellent cues are involved in how vagal axons reach specific targets. We tested the hypothesis that Slit/Robo chemorepulsion can contribute to the restriction of vagal sensory axons to specific targets in the gut wall.
  
  
  RESULTS
  Transcripts encoding Robo1 and Robo2 were expressed in the nodose ganglia throughout development and mRNA encoding the Robo ligands Slit1, Slit2, and Slit3 were all found in the fetal and adult bowel. Slit2 protein was located in the outer gut mesenchyme in regions that partially overlap with the secretion of netrin-1. Neurites extending from explanted nodose ganglia were repelled by Slit2.
  
  
  CONCLUSIONS
  These observations suggest that vagal sensory axons are responsive to Slit proteins and are thus repelled by Slits secreted in the gut wall and prevented from reaching inappropriate targets.
authors.affiliation: School of Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Goldberg
authors.forename: Rajka
authors.initials: R
authors.lastname: Borojevic
authors.forename: Monique
authors.initials: M
authors.lastname: Anderson
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Chen
authors.forename: Michael D
authors.initials: MD
authors.lastname: Gershon
authors.forename: Elyanne M
authors.initials: EM
authors.lastname: Ratcliffe
mesh_terms: D000818:Animals; D002633:Chemotaxis / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D005333:Fetus / Q000196:embryology; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007420:Intestine, Large / Q000294:innervation* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000502:physiology*; D046509:Tissue Culture Techniques; D014630:Vagus Nerve / Q000502:physiology*; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C498888:Robo2 protein, mouse; C120010:Slit1 protein, mouse; C432251:Slit3 protein, mouse