title: Reelin controls progenitor cell migration in the healthy and pathological adult mouse brain.
abstract: Understanding the signals that control migration of neural progenitor cells in the adult brain may provide new therapeutic opportunities. Reelin is best known for its role in regulating cell migration during brain development, but we now demonstrate a novel function for reelin in the injured adult brain. First, we show that Reelin is upregulated around lesions. Second, experimentally increasing Reelin expression levels in healthy mouse brain leads to a change in the migratory behavior of subventricular zone-derived progenitors, triggering them to leave the rostral migratory stream (RMS) to which they are normally restricted during their migration to the olfactory bulb. Third, we reveal that Reelin increases endogenous progenitor cell dispersal in periventricular structures independently of any chemoattraction but via cell detachment and chemokinetic action, and thereby potentiates spontaneous cell recruitment to demyelination lesions in the corpus callosum. Conversely, animals lacking Reelin signaling exhibit reduced endogenous progenitor recruitment at the lesion site. Altogether, these results demonstrate that beyond its known role during brain development, Reelin is a key player in post-lesional cell migration in the adult brain. Finally our findings provide proof of concept that allowing progenitors to escape from the RMS is a potential therapeutic approach to promote myelin repair.
authors.affiliation: Institut de Biologie du Développement de Marseille Luminy, CNRS, Université de la Méditerranée, Marseille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Courtès
authors.forename: Julien
authors.initials: J
authors.lastname: Vernerey
authors.forename: Lluís
authors.initials: L
authors.lastname: Pujadas
authors.forename: Karine
authors.initials: K
authors.lastname: Magalon
authors.forename: Harold
authors.initials: H
authors.lastname: Cremer
authors.forename: Eduardo
authors.initials: E
authors.lastname: Soriano
authors.forename: Pascale
authors.initials: P
authors.lastname: Durbec
authors.forename: Myriam
authors.initials: M
authors.lastname: Cayre
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002552:Cerebral Ventricles / Q000166:cytology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006262:Health; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases