2026-06-01T04:37:54Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/323232026-02-03T11:24:23Zcom_10630_2254col_10630_37953

00925njm 22002777a 4500 dc Deboux, Cyrille author Spigoni, C. author Garcia Diaz, Beatriz author Ypsilanti, A. author Sarrazin, Nadege author Bachelin, Corinne author Chédotal, Alain author Baron Van Evercooren, Anne author 2020 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. 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 https://hdl.handle.net/10630/32323 10.3389/fncel.2020.00168 Redes nerviosas Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS