β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain
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Teppei Fujioka, Naoko Kaneko, Itsuki Ajioka, Kanako Nakaguchi, Taichi Omata, Honoka Ohba, Reinhard Fässler, José Manuel García-Verdugo, Kiyotoshi Sekiguchi, Noriyuki Matsukawa, and Kazunobu Sawamoto, "β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain", EBioMedicine, 16, 195-203, Elsevier, 2017
Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatmentto promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, im-mature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricularzone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increasethe number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for is-chemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficientneuronal regeneration. To move toward the lesion, neuroblasts form chain-like aggregates and migrate alongblood vessels, which are thought to increase their migration efficiency. However, the molecular mechanisms reg-ulating thesemigration processesare largely unknown. Here we studied the role ofβ1-class integrins, transmem-brane receptors for extracellular matrix proteins, in these migrating neuroblasts. We found that the neuroblastchain formation and blood vessel-guided migration critically depend onβ1 integrin signaling.β1 integrin facili-tated the adhesion of neuroblasts to laminin and the efficient translocation of their soma during migration. More-over, artificial laminin-containing scaffolds promoted neuroblast chain formation and migration toward theinjured area. These data suggest that laminin signaling viaβ1 integrin supports vasculature-guided neuronal mi-gration to efficiently supply neuroblasts to injured areas. This study also highlights the importance of vascularscaffolds for cell migration in development and regeneration.
EBioMedicine (16), 195-203, 2017-02