Reelin controls progenitor cell migration in the healty and pathological adult brain

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 b...

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Detalles Bibliográficos
Autores: Courtès, Sandrine, Vernerey, Julien, Pujadas Puigdomènech, Lluís, Magalon, Karine, Cremer, Harold, Soriano García, Eduardo, Durbec, Pascale, Cayre, Myriam
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/148187
Acceso en línea:https://hdl.handle.net/2445/148187
Access Level:acceso abierto
Palabra clave:Neurobiologia del desenvolupament
Hipocamp (Cervell)
Developmental neurobiology
Hippocampus (Brain)
Descripción
Sumario: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.