SlitC-PlexinA1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plate
- Institut NeuroMyoGène - CNRS UMR 5310 - INSERM U1217 de Lyon- UCBL Lyon 1, France
- University of Bordeaux, France
Abstract
Spinal commissural axon navigation across the midline in the floor plate requires repulsive forces from local Slit repellents. The long-held view is that Slits push growth cones forward and prevent them from turning back once they became sensitized to these cues after midline crossing. We analyzed with fluorescent reporters Slits distribution and FP glia morphology. We observed clusters of Slit-N and Slit-C fragments decorating a complex architecture of glial basal process ramifications. We found that PC2 proprotein convertase activity contributes to this ligands pattern. Next, we studied Slit-C acting via PlexinA1 receptor shared with another FP repellent, the Semaphorin3B, through generation of a mouse model baring PlexinA1Y1815F mutation abrogating SlitC but not Sema3B responsiveness, manipulations in the chicken embryo and ex vivo live imaging. This revealed a guidance mechanism by which SlitC constantly limits growth cone exploration, imposing ordered and forward-directed progression through aligned corridors formed by FP basal ramifications.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for figures.
Article and author information
Author details
Servane Tauszig-Delamasure
Valerie Castellani
Funding
Agence Nationale de la Recherche (ANR-11-IDEX-0007)
- Valerie Castellani
Fondation pour la Recherche Médicale (Label team)
- Valerie Castellani
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Ducuing et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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SlitC-PlexinA1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plate
eLife 9:e63205.
https://doi.org/10.7554/eLife.63205
