SlitC-PlexinA1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plate
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 w...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/63205 |
| _version_ | 1811181470544297984 |
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| author | Hugo Ducuing Thibault Gardette Aurora Pignata Karine Kindbeiter Muriel Bozon Olivier Thoumine Céline Delloye-Bourgeois Servane Tauszig-Delamasure Valerie Castellani |
| author_facet | Hugo Ducuing Thibault Gardette Aurora Pignata Karine Kindbeiter Muriel Bozon Olivier Thoumine Céline Delloye-Bourgeois Servane Tauszig-Delamasure Valerie Castellani |
| author_sort | Hugo Ducuing |
| collection | DOAJ |
| description | 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 pattern of ligands. 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. |
| first_indexed | 2024-04-11T09:18:17Z |
| format | Article |
| id | doaj.art-9dea68b98dc34fea99b7095569b511ca |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:18:17Z |
| publishDate | 2020-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-9dea68b98dc34fea99b7095569b511ca2022-12-22T04:32:16ZengeLife Sciences Publications LtdeLife2050-084X2020-12-01910.7554/eLife.63205SlitC-PlexinA1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plateHugo Ducuing0https://orcid.org/0000-0001-8227-7924Thibault Gardette1Aurora Pignata2Karine Kindbeiter3Muriel Bozon4Olivier Thoumine5https://orcid.org/0000-0002-8041-1349Céline Delloye-Bourgeois6Servane Tauszig-Delamasure7https://orcid.org/0000-0003-4926-0199Valerie Castellani8https://orcid.org/0000-0001-9623-9312Institut NeuroMyoGène - CNRS UMR 5310 - INSERM U1217 de Lyon- UCBL Lyon 1, Faculté de Médecine et de Pharmacie, Lyon, FranceInstitut NeuroMyoGène - CNRS UMR 5310 - INSERM U1217 de Lyon- UCBL Lyon 1, Faculté de Médecine et de Pharmacie, Lyon, FranceInstitut NeuroMyoGène - CNRS UMR 5310 - INSERM U1217 de Lyon- UCBL Lyon 1, Faculté de Médecine et de Pharmacie, Lyon, FranceInstitut NeuroMyoGène - CNRS UMR 5310 - INSERM U1217 de Lyon- UCBL Lyon 1, Faculté de Médecine et de Pharmacie, Lyon, FranceInstitut NeuroMyoGène - CNRS UMR 5310 - INSERM U1217 de Lyon- UCBL Lyon 1, Faculté de Médecine et de Pharmacie, Lyon, FranceInterdisciplinary Institute for Neuroscience, UMR CNRS 5297 - University of Bordeaux, Bordeaux, FranceInstitut NeuroMyoGène - CNRS UMR 5310 - INSERM U1217 de Lyon- UCBL Lyon 1, Faculté de Médecine et de Pharmacie, Lyon, FranceInstitut NeuroMyoGène - CNRS UMR 5310 - INSERM U1217 de Lyon- UCBL Lyon 1, Faculté de Médecine et de Pharmacie, Lyon, FranceInstitut NeuroMyoGène - CNRS UMR 5310 - INSERM U1217 de Lyon- UCBL Lyon 1, Faculté de Médecine et de Pharmacie, Lyon, FranceSpinal 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 pattern of ligands. 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.https://elifesciences.org/articles/63205axon guidancecommissural axonsmidline crossing |
| spellingShingle | Hugo Ducuing Thibault Gardette Aurora Pignata Karine Kindbeiter Muriel Bozon Olivier Thoumine Céline Delloye-Bourgeois Servane Tauszig-Delamasure Valerie Castellani SlitC-PlexinA1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plate eLife axon guidance commissural axons midline crossing |
| title | SlitC-PlexinA1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plate |
| title_full | SlitC-PlexinA1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plate |
| title_fullStr | SlitC-PlexinA1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plate |
| title_full_unstemmed | SlitC-PlexinA1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plate |
| title_short | SlitC-PlexinA1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plate |
| title_sort | slitc plexina1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plate |
| topic | axon guidance commissural axons midline crossing |
| url | https://elifesciences.org/articles/63205 |
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