Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS
Slit1 is a secreted axon guidance molecule, also involved in adult neurogenesis. In physiological conditions, Slit1 loss promotes ectopic dispersal of SVZ-derived neural precursors (SVZ-NPCs) into periventricular structures such as the corpus callosum. Demyelination of the corpus callosum triggers S...
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doaj-a0a5ffcf85474186a05f6a04f6e23c622020-11-25T03:12:34ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-06-011410.3389/fncel.2020.00168527063Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNSC. Deboux0G. Spigoni1C. Caillava2B. Garcia-Diaz3A. Ypsilanti4N. Sarrazin5C. Bachelin6A. Chédotal7A. Baron-Van Evercooren8Institut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, FranceInstitut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, FranceInstitut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, FranceInstitut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, FranceInstitut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, FranceInstitut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, FranceInstitut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, FranceInstitut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, FranceInstitut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, FranceSlit1 is a secreted axon guidance molecule, also involved in adult neurogenesis. In physiological conditions, Slit1 loss promotes ectopic dispersal of SVZ-derived neural precursors (SVZ-NPCs) into periventricular structures such as the corpus callosum. Demyelination of the corpus callosum triggers SVZ-NPC migration to ectopic locations and their recruitment by the lesion, suggesting a possible role for Slit1 in SVZ-NPCs ectopic dispersal regulation in pathological conditions. Here, we have investigated the function of Slit1 protein in the recruitment of SVZ-NPCs after CNS demyelination. We find that the dynamics of oligodendrogenesis and temporal profile of developmental myelination in Slit1–/– mice are similar to Slit1+/− controls. SVZ micro-dissection and RT-PCR from wild-type mice, show that Slits and Robos are physiologically regulated at the transcriptional level in response to corpus callosum demyelination suggesting their role in the process of SVZ-NPC ectopic migration in demyelinating conditions. Moreover, we find that the number of SVZ-NPCs recruited by the lesion increases in Sli1–/– mice compared to Slit1+/− mice, leading to higher numbers of Olig2+ cells within the lesion. Time-lapse video-microscopy of immuno-purified NPCs shows that Slit1-deficient cells migrate faster and make more frequent directional changes than control NPCs, supporting a cell-autonomous mechanism of action of Slit1 in NPC migration. In conclusion, while Slit1 does not affect the normal developmental process of oligodendrogenesis and myelination, it regulates adult SVZ-NPC ectopic migration in response to demyelination, and consequently oligodendrocyte renewal within the lesion.https://www.frontiersin.org/article/10.3389/fncel.2020.00168/fullSlit1neural precursoroligodendrocytesrecruitmentmigrationmyelin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
C. Deboux G. Spigoni C. Caillava B. Garcia-Diaz A. Ypsilanti N. Sarrazin C. Bachelin A. Chédotal A. Baron-Van Evercooren |
spellingShingle |
C. Deboux G. Spigoni C. Caillava B. Garcia-Diaz A. Ypsilanti N. Sarrazin C. Bachelin A. Chédotal A. Baron-Van Evercooren Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS Frontiers in Cellular Neuroscience Slit1 neural precursor oligodendrocytes recruitment migration myelin |
author_facet |
C. Deboux G. Spigoni C. Caillava B. Garcia-Diaz A. Ypsilanti N. Sarrazin C. Bachelin A. Chédotal A. Baron-Van Evercooren |
author_sort |
C. Deboux |
title |
Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS |
title_short |
Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS |
title_full |
Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS |
title_fullStr |
Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS |
title_full_unstemmed |
Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS |
title_sort |
slit1 protein regulates svz-derived precursor mobilization in the adult demyelinated cns |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2020-06-01 |
description |
Slit1 is a secreted axon guidance molecule, also involved in adult neurogenesis. In physiological conditions, Slit1 loss promotes ectopic dispersal of SVZ-derived neural precursors (SVZ-NPCs) into periventricular structures such as the corpus callosum. Demyelination of the corpus callosum triggers SVZ-NPC migration to ectopic locations and their recruitment by the lesion, suggesting a possible role for Slit1 in SVZ-NPCs ectopic dispersal regulation in pathological conditions. Here, we have investigated the function of Slit1 protein in the recruitment of SVZ-NPCs after CNS demyelination. We find that the dynamics of oligodendrogenesis and temporal profile of developmental myelination in Slit1–/– mice are similar to Slit1+/− controls. SVZ micro-dissection and RT-PCR from wild-type mice, show that Slits and Robos are physiologically regulated at the transcriptional level in response to corpus callosum demyelination suggesting their role in the process of SVZ-NPC ectopic migration in demyelinating conditions. Moreover, we find that the number of SVZ-NPCs recruited by the lesion increases in Sli1–/– mice compared to Slit1+/− mice, leading to higher numbers of Olig2+ cells within the lesion. Time-lapse video-microscopy of immuno-purified NPCs shows that Slit1-deficient cells migrate faster and make more frequent directional changes than control NPCs, supporting a cell-autonomous mechanism of action of Slit1 in NPC migration. In conclusion, while Slit1 does not affect the normal developmental process of oligodendrogenesis and myelination, it regulates adult SVZ-NPC ectopic migration in response to demyelination, and consequently oligodendrocyte renewal within the lesion. |
topic |
Slit1 neural precursor oligodendrocytes recruitment migration myelin |
url |
https://www.frontiersin.org/article/10.3389/fncel.2020.00168/full |
work_keys_str_mv |
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