RRC ID 55797
Author Kaneko N, Herranz-Pérez V, Otsuka T, Sano H, Ohno N, Omata T, Nguyen HB, Thai TQ, Nambu A, Kawaguchi Y, García-Verdugo JM, Sawamoto K.
Title New neurons use Slit-Robo signaling to migrate through the glial meshwork and approach a lesion for functional regeneration.
Journal Sci Adv
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.
Volume 4(12)
Pages eaav0618
Published 2018-12-1
DOI 10.1126/sciadv.aav0618
PII aav0618
PMID 30547091
PMC PMC6291311
MeSH Actin Cytoskeleton / chemistry Actin Cytoskeleton / metabolism Animals Astrocytes / metabolism Brain / metabolism Cell Movement Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* Male Mice Mice, Knockout Neurogenesis* Neuroglia / metabolism* Neurons / metabolism* Protein Binding Protein Multimerization Receptors, Immunologic / genetics Receptors, Immunologic / metabolism* Regeneration* Signal Transduction* cdc42 GTP-Binding Protein / metabolism
IF 12.804
Times Cited 9
DNA material CSII-CMV-RfA-IRES2-Venus (RDB04388)