Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan; Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Cell Stem Cell. 2018 Jan 4;22(1):128-137.e9. doi: 10.1016/j.stem.2017.11.005. Epub 2017 Dec 21.
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.
放射状胶质细胞（RG）是胚胎神经干细胞（NSC），可产生神经母细胞，并提供纤维作为胚胎发育过程中神经母细胞迁移的支架。尽管它们通常在出生后很快消失，但在这里我们发现 RG 纤维可以在受伤的新生小鼠大脑中持续存在，并作为从脑室下区（V-SVZ）衍生的神经母细胞迁移到损伤部位的支架。这种损伤诱导的 RG 纤维维持具有出生后发育过程中的有限时间窗口，并通过促进 RhoA 激活的 N-钙粘蛋白介导的细胞-细胞接触促进神经母细胞的定向跳跃运动。将含有 N-钙粘蛋白的支架移植到受伤的新生大脑中同样可以促进 V-SVZ 衍生的神经母细胞的迁移和成熟，从而改善受损步态行为的功能。这些结果表明，RG 纤维使 V-SVZ 衍生的神经母细胞能够向损伤部位迁移，从而增强神经元再生和从新生儿脑损伤中恢复功能。
