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dc.contributor.authorArmenteros, Tomás
dc.contributor.authorAndreu, Zoraida
dc.contributor.authorHortigüela, Rafael 
dc.contributor.authorLie, D Chichung
dc.contributor.authorMira, Helena
dc.identifier.citationSci Rep. 2018 Jun 18;8(1):9241.es_ES
dc.description.abstractNeuronal production from neural stem cells persists during adulthood in the subgranular zone of the hippocampal dentate gyrus. Extracellular signals provided by the hippocampal microenvironment regulate the neuronal fate commitment of the stem cell progeny. To date, the identity of those signals and their crosstalk has been only partially resolved. Here we show that adult rat hippocampal neural stem and progenitor cells (AH-NSPCs) express receptors for bone morphogenetic proteins (BMPs) and that the BMP/P-Smad pathway is active in AH-NSPCs undergoing differentiation towards the neuronal lineage. In vitro, exposure to the BMP2 and BMP4 ligands is sufficient to increase neurogenesis from AH-NSPCs in a WNT dependent manner while decreasing oligodendrogenesis. Moreover, BMP2/4 and WNT3A, a key regulator of adult hippocampal neurogenesis, cooperate to further enhance neuronal production. Our data point to a mechanistic convergence of the BMP and WNT pathways at the level of the T-cell factor/lymphoid enhancer factor gene Lef1. Altogether, we provide evidence that BMP signalling is an important regulator for the neuronal fate specification of AH-NSPCs cultures and we show that it significantly cooperates with the previously described master regulator of adult hippocampal neurogenesis, the WNT signalling pathway.es_ES
dc.description.sponsorshipWe thank Prof. Kinichi Nakashima for providing the caBMPR1a retroviral construct. This work was supported by the Spanish Ministerio de Economía y Competitividad (grant number SAF2015-70433-R).es_ES
dc.publisherNature Publishing Group es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshBone Morphogenetic Protein 2 es_ES
dc.subject.meshBone Morphogenetic Protein 4 es_ES
dc.subject.meshCell Differentiation es_ES
dc.subject.meshDentate Gyrus es_ES
dc.subject.meshHippocampus es_ES
dc.subject.meshLymphoid Enhancer-Binding Factor 1 es_ES
dc.subject.meshMice es_ES
dc.subject.meshNeural Stem Cells es_ES
dc.subject.meshNeurogenesis es_ES
dc.subject.meshNeurons es_ES
dc.subject.meshRats es_ES
dc.subject.meshTCF Transcription Factors es_ES
dc.subject.meshWnt Proteins es_ES
dc.subject.meshWnt Signaling Pathway es_ES
dc.titleBMP and WNT signalling cooperate through LEF1 in the neuronal specification of adult hippocampal neural stem and progenitor cellses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.identifier.journalScientific reportses_ES
dc.repisalud.centroISCIII::Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)es_ES
dc.rights.accessRightsopen accesses_ES

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Atribución 4.0 Internacional
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