RT Journal Article
T1 Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS
A1 Deboux, Cyrille
A1 Spigoni, C.
A1 Garcia Diaz, Beatriz
A1 Ypsilanti, A.
A1 Sarrazin, Nadege
A1 Bachelin, Corinne
A1 Chédotal, Alain
A1 Baron Van Evercooren, Anne
K1 Redes nerviosas
AB 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.
PB Frontiers Media
YR 2020
FD 2020
LK https://hdl.handle.net/10630/32323
UL https://hdl.handle.net/10630/32323
LA eng
NO Deboux C, Spigoni G, Caillava C, Garcia-Diaz B, Ypsilanti A, Sarrazin N, Bachelin C, Chédotal A and Baron-Van Evercooren A (2020) Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS. Front. Cell. Neurosci. 14:168. doi: 10.3389/fncel.2020.00168
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026