Tissue stiffness controls neuroblast migratory behavior and reprogramming during myelin repair

After brain insults, neuronal progenitors of the adult mouse sub-ventricular zone can change migration mode to emigrate toward lesioned tissues and participate in regenerative processes. During demyelination, these progenitors change fate to generate oligodendrocytes that contribute to myelin replacement. Herein, we examined the possible link between neuroblast behavior and mechanical tissue properties. Using sub-ventricular zone organotypic explant, we found that matrix stiffness influences neuroblast migratory mode and fate. A softer matrix promotes a switch from collective (chain) to isolated cell migration and reprogramming into oligodendrocytes. Nanoindentation on fresh brain slices provided evidence for changes in the mechanical properties of the corpus callosum following lysophosphatidylcholine-induced focal demyelination. In particular, we propose that the decrease in stiffness may be due to myelin loss and extracellular matrix modification. Overall, our work suggests that postlesional changes in mechanical cues regulate neuroblast mobilization and fate conversion in the adult mammalian central nervous system.