Cell Stem Cell
Volume 22, Issue 1, 4 January 2018, Pages 128-137.e9
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Short Article
Radial Glial Fibers Promote Neuronal Migration and Functional Recovery after Neonatal Brain Injury

https://doi.org/10.1016/j.stem.2017.11.005Get rights and content
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Highlights

  • 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

Summary

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.

Keywords

neonatal brain injury
postnatal neurogenesis
ventricular-subventricular zone
radial glial cell
neuronal migration
neuronal regeneration
gait behavior
N-cadherin

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