Slit/Robo‐mediated chemorepulsion of vagal sensory axons in the fetal gut

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 w...

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Published in:Developmental dynamics 2013-01, Vol.242 (1), p.9-15
Main Authors: Goldberg, David, Borojevic, Rajka, Anderson, Monique, Chen, Jason J., Gershon, Michael D., Ratcliffe, Elyanne M.
Format: Article
Language:English
Subjects:
Animals
axon guidance
Chemotaxis - physiology
DNA Primers - genetics
enteric nervous system
Fetus - embryology
gastrointestinal tract
HEK293 Cells
Humans
Immunohistochemistry
Intercellular Signaling Peptides and Proteins - metabolism
Intestine, Large - innervation
Intestine, Large - metabolism
Membrane Proteins - metabolism
Mice
Nerve Tissue Proteins - metabolism
nodose ganglion
Real-Time Polymerase Chain Reaction
Receptors, Immunologic - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Roundabout Proteins
Sensory Receptor Cells - physiology
Tissue Culture Techniques
vagus nerve
Vagus Nerve - physiology
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Summary: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. Developmental Dynamics 242:9–15, 2013. © 2012 Wiley Periodicals, Inc. Key Findings: Transcripts encoding Robo1 and Robo2 are expressed in developing and adult nodose ganglia. Transcripts encoding Slit1, Slit2 and Slit3 are expressed in developing and adult gut. Slit2 protein is located in the outer gut mesenchyme. Neurites extending from explanted nodose ganglia are repelled by Slit2 in vitro. Slit/Robo chemorepulsion may contribute to the establishment of the vagal sensory innervation of the fetal gut.
ISSN:1058-8388
1097-0177
DOI:10.1002/dvdy.23898