Programming of neural progenitors of the adult subependymal zone towards a glutamatergic neuron lineage by neurogenin 2

Although adult subependymal zone (SEZ) neural stem cells mostly generate GABAergic interneurons, a small progenitor population expresses the proneural gene Neurog2 and produces glutamatergic neurons. Here, we determined whether Neurog2 could respecify SEZ neural stem cells and their progeny toward a...

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Detalles Bibliográficos
Autores: Péron, Sophie, Miyakoshi, Leo M., Brill, Monika S., Manzano Franco, Diana, Serrano López, Julia, Fan, Wenqiang, Marichal, Nicolás, Ghanem, Alexander, Conzelmann, Karl-Klaus, Karow, Marisa, Ortega De La O, Felipe, Gascón Jiménez, Sergio, Berninger, Benedikt
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/104218
Acceso en línea:https://hdl.handle.net/20.500.14352/104218
Access Level:acceso abierto
Palabra clave:577.1/2
Adult neurogenesis
Neural specification
Neural stem cell
Neurogenin 2
Adult subventricular zone
Olfactory bulb
Fate reprogramming
Proneural gene
Bioquímica (Biología)
Biología molecular (Biología)
2403 Bioquímica
Descripción
Sumario:Although adult subependymal zone (SEZ) neural stem cells mostly generate GABAergic interneurons, a small progenitor population expresses the proneural gene Neurog2 and produces glutamatergic neurons. Here, we determined whether Neurog2 could respecify SEZ neural stem cells and their progeny toward a glutamatergic fate. Retrovirus-mediated expression of Neurog2 induced the glutamatergic lineage markers TBR2 and TBR1 in cultured SEZ progenitors, which differentiated into functional glutamatergic neurons. Likewise, Neurog2-transduced SEZ progenitors acquired glutamatergic neuron hallmarks in vivo. Intriguingly, they failed to migrate toward the olfactory bulb and instead differentiated within the SEZ or the adjacent striatum, where they received connections from local neurons, as indicated by rabies virus-mediated monosynaptic tracing. In contrast, lentivirus-mediated expression of Neurog2 failed to reprogram early SEZ neurons, which maintained GABAergic identity and migrated to the olfactory bulb. Our data show that NEUROG2 can program SEZ progenitors toward a glutamatergic identity but fails to reprogram their neuronal progeny.

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