Frizzled-1 receptor regulates adult hippocampal neurogenesis

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dc.contributor.authorInestrosa Cantín, Nibaldo
dc.contributor.authorMardones, Muriel D.
dc.contributor.authorAndaur, Gabriela A.
dc.contributor.authorVaras-Godoy, Manuel
dc.contributor.authorHenriquez, Jenny F.
dc.contributor.authorSalech, Felipe
dc.contributor.authorBehrens, María I.
dc.contributor.authorCouve, Andrés
dc.contributor.authorVarela-Nallar, Lorena
dc.date.accessioned2019-10-17T15:21:24Z
dc.date.available2019-10-17T15:21:24Z
dc.date.issued2016
dc.date.updated2019-10-14T18:50:39Z
dc.description.abstractAbstract Background In the adult hippocampus new neurons are continuously generated from neural stem cells (NSCs) present at the subgranular zone of the dentate gyrus. This process is controlled by Wnt signaling, which plays a complex role in regulating multiple steps of neurogenesis including maintenance, proliferation and differentiation of progenitor cells and the development of newborn neurons. Differential effects of Wnt signaling during progression of neurogenesis could be mediated by cell-type specific expression of Wnt receptors. Here we studied the potential role of Frizzled-1 (FZD1) receptor in adult hippocampal neurogenesis. Results In the adult dentate gyrus, we determined that FZD1 is highly expressed in NSCs, neural progenitors and immature neurons. Accordingly, FZD1 is expressed in cultured adult hippocampal progenitors isolated from mouse brain. To evaluate the role of this receptor in vivo we targeted FZD1 in newborn cells using retroviral-mediated RNA interference. FZD1 knockdown resulted in a marked decrease in the differentiation of newborn cells into neurons and increased the generation of astrocytes, suggesting a regulatory role for the receptor in cell fate commitment. In addition, FZD1 knockdown induced an extended migration of adult-born neurons within the granule cell layer. However, no differences were observed in total dendritic length and dendritic arbor complexity between control and FZD1-deficient newborn neurons. Conclusions Our results show that FZD1 regulates specific stages of adult hippocampal neurogenesis, being required for neuronal differentiation and positioning of newborn neurons into the granule cell layer, but not for morphological development of adult-born granule neurons.Abstract Background In the adult hippocampus new neurons are continuously generated from neural stem cells (NSCs) present at the subgranular zone of the dentate gyrus. This process is controlled by Wnt signaling, which plays a complex role in regulating multiple steps of neurogenesis including maintenance, proliferation and differentiation of progenitor cells and the development of newborn neurons. Differential effects of Wnt signaling during progression of neurogenesis could be mediated by cell-type specific expression of Wnt receptors. Here we studied the potential role of Frizzled-1 (FZD1) receptor in adult hippocampal neurogenesis. Results In the adult dentate gyrus, we determined that FZD1 is highly expressed in NSCs, neural progenitors and immature neurons. Accordingly, FZD1 is expressed in cultured adult hippocampal progenitors isolated from mouse brain. To evaluate the role of this receptor in vivo we targeted FZD1 in newborn cells using retroviral-mediated RNA interference. FZD1 knockdown resulted in a marked decrease in the differentiation of newborn cells into neurons and increased the generation of astrocytes, suggesting a regulatory role for the receptor in cell fate commitment. In addition, FZD1 knockdown induced an extended migration of adult-born neurons within the granule cell layer. However, no differences were observed in total dendritic length and dendritic arbor complexity between control and FZD1-deficient newborn neurons. Conclusions Our results show that FZD1 regulates specific stages of adult hippocampal neurogenesis, being required for neuronal differentiation and positioning of newborn neurons into the granule cell layer, but not for morphological development of adult-born granule neurons.
dc.fuente.origenBiomed Central
dc.identifier.citationMolecular Brain. 2016 Mar 15;9(1):29
dc.identifier.doi10.1186/s13041-016-0209-3
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/26766
dc.identifier.wosidWOS:000372113800001
dc.issue.numeroNo. 29
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final12
dc.pagina.inicio1
dc.revistaMolecular Braines_ES
dc.rightsacceso abierto
dc.rights.holderMardones et al.
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.subject.otherNeurogénesises_ES
dc.subject.otherNeuronas - Proteínases_ES
dc.subject.otherHipocampo (Cerebro)es_ES
dc.titleFrizzled-1 receptor regulates adult hippocampal neurogenesises_ES
dc.typeartículo
dc.volumenVol. 9
sipa.codpersvinculados99331
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