Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS

Frontiers in Cellular Neuroscience
C DebouxAnne Baron-Van Evercooren

Abstract

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-puri...Continue Reading

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Citations

May 4, 2021·Frontiers in Cellular Neuroscience·Myriam CayrePascale Durbec

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Methods Mentioned

BETA
PCR
dissections
electron microscopy
transgenic

Software Mentioned

Metamorph
ImageJ
Image
GraphPad Prism

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