New neurons use slit-robo signaling to migrate through the glial meshwork and approach a lesion for functional regeneration

N. Kaneko, V. Herranz-Pérez, T. Otsuka, H. Sano, N. Ohno, T. Omata, H. B. Nguyen, T. Q. Thai, A. Nambu, Y. Kawaguchi, J. M. García-Verdugo, K. Sawamoto

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

After brain injury, neural stem cell–derived neuronal precursors (neuroblasts) in the ventricular-subventricular zone migrate toward the lesion. However, the ability of the mammalian brain to regenerate neuronal circuits for functional recovery is quite limited. Here, using a mouse model for ischemic stroke, we show that neuroblast migration is restricted by reactive astrocytes in and around the lesion. To migrate, the neuroblasts use Slit1-Robo2 signaling to disrupt the actin cytoskeleton in reactive astrocytes at the site of contact. Slit1-overexpressing neuroblasts transplanted into the poststroke brain migrated closer to the lesion than did control neuroblasts. These neuroblasts matured into striatal neurons and efficiently regenerated neuronal circuits, resulting in functional recovery in the poststroke mice. These results suggest that the positioning of new neurons will be critical for functional neuronal regeneration in stem/progenitor cell–based therapies for brain injury.

Original languageEnglish
Article numbereaav0618
JournalScience advances
Volume4
Issue number12
DOIs
Publication statusPublished - 12-12-2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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