Radial Glial Fibers Promote Neuronal Migration and Functional Recovery after Neonatal Brain Injury

• Published in: Cell stem cell Vol. 22; no. 1; pp. 128 - 137.e9
• Main Authors: Jinnou, Hideo, Sawada, Masato, Kawase, Koya, Kaneko, Naoko, Herranz-Pérez, Vicente, Miyamoto, Takuya, Kawaue, Takumi, Miyata, Takaki, Tabata, Yasuhiko, Akaike, Toshihiro, García-Verdugo, José Manuel, Ajioka, Itsuki, Saitoh, Shinji, Sawamoto, Kazunobu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.01.2018
• Subjects: Animals; Animals, Newborn; Brain Injuries - pathology; Brain Injuries - physiopathology; Cadherins - metabolism; Cell Movement; gait behavior; Lateral Ventricles - pathology; N-cadherin; neonatal brain injury; Neuroglia - metabolism; Neuroglia - pathology; Neuroglia - ultrastructure; neuronal migration; neuronal regeneration; Neurons - metabolism; Neurons - pathology; Neurons - ultrastructure; postnatal neurogenesis; radial glial cell; Recovery of Function; rhoA GTP-Binding Protein - metabolism; ventricular-subventricular zone; radial glial cell; ventricular-subventricular zone; gait behavior; N-cadherin; neuronal migration; postnatal neurogenesis; neonatal brain injury; neuronal regeneration
• ISSN: 1934-5909; 1875-9777; 1875-9777
• DOI: 10.1016/j.stem.2017.11.005

Radial glia (RG) are embryonic neural stem cells (NSCs) that produce neuroblasts and provide fibers that act as a scaffold for neuroblast migration during embryonic development. Although they normally disappear soon after birth, here we found that RG fibers can persist in injured neonatal mouse brains and act as a scaffold for postnatal ventricular-subventricular zone (V-SVZ)-derived neuroblasts that migrate to the lesion site. This injury-induced maintenance of RG fibers has a limited time window during post-natal development and promotes directional saltatory movement of neuroblasts via N-cadherin-mediated cell-cell contacts that promote RhoA activation. Transplanting an N-cadherin-containing scaffold into injured neonatal brains likewise promotes migration and maturation of V-SVZ-derived neuroblasts, leading to functional improvements in impaired gait behaviors. Together these results suggest that RG fibers enable postnatal V-SVZ-derived neuroblasts to migrate toward sites of injury, thereby enhancing neuronal regeneration and functional recovery from neonatal brain injuries. [Display omitted] •Embryonic radial glia fibers persist in neonatal animals after brain injury•V-SVZ-derived neuroblasts migrate along retained radial fibers toward injured cortex•N-cadherin-dependent homophilic adhesion promotes fiber-guided neuronal migration•N-cadherin-containing scaffolds promote neuronal regeneration and functional recovery Radial glia cells generate neuroblasts during embryonic cortical development and disappear soon after birth. Sawamoto and colleagues show that radial glia fibers are maintained in neonatal cortex in response to brain injury and support migration of postnatal V-SVZ-derived neurons, leading to behavioral recovery