| http://purl.uniprot.org/citations/35514236 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35514236 | http://www.w3.org/2000/01/rdf-schema#comment | "Neural tube defects (NTDs) are among the common and severe birth defects with poorly understood etiology. Mutations in the Wnt co-receptor LRP6 are associated with NTDs in humans. Either gain-of-function (GOF) or loss-of-function (LOF) mutations of Lrp6 can cause NTDs in mice. NTDs in Lrp6-GOF mutants may be attributed to altered β-catenin-independent noncanonical Wnt signaling. However, the mechanisms underlying NTDs in Lrp6-LOF mutants and the role of Lrp6-mediated canonical Wnt/β-catenin signaling in neural tube closure remain unresolved. We previously demonstrated that β-catenin signaling is required for posterior neuropore (PNP) closure. In the current study, conditional ablation of Lrp6 in dorsal PNP caused spinal NTDs with diminished activities of Wnt/β-catenin signaling and its downstream target gene Pax3, which is required for PNP closure. β-catenin-GOF rescued NTDs in Lrp6-LOF mutants. Moreover, maternal supplementation of a Wnt/β-catenin signaling agonist reduced the frequency and severity of spinal NTDs in Lrp6-LOF mutants by restoring Pax3 expression. Together, these results demonstrate the essential role of Lrp6-mediated Wnt/β-catenin signaling in PNP closure, which could also provide a therapeutic target for NTD intervention through manipulation of canonical Wnt/β-catenin signaling activities."xsd:string |
| http://purl.uniprot.org/citations/35514236 | http://purl.org/dc/terms/identifier | "doi:10.1242/dmm.049517"xsd:string |
| http://purl.uniprot.org/citations/35514236 | http://purl.uniprot.org/core/author | "Saha S.K."xsd:string |
| http://purl.uniprot.org/citations/35514236 | http://purl.uniprot.org/core/author | "Zhou C.J."xsd:string |
| http://purl.uniprot.org/citations/35514236 | http://purl.uniprot.org/core/author | "Zhao T."xsd:string |
| http://purl.uniprot.org/citations/35514236 | http://purl.uniprot.org/core/author | "Reynolds K."xsd:string |
| http://purl.uniprot.org/citations/35514236 | http://purl.uniprot.org/core/author | "McMahon M."xsd:string |
| http://purl.uniprot.org/citations/35514236 | http://purl.uniprot.org/core/author | "Stokes A."xsd:string |
| http://purl.uniprot.org/citations/35514236 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35514236 | http://purl.uniprot.org/core/name | "Dis Model Mech"xsd:string |
| http://purl.uniprot.org/citations/35514236 | http://purl.uniprot.org/core/pages | "dmm049517"xsd:string |
| http://purl.uniprot.org/citations/35514236 | http://purl.uniprot.org/core/title | "The role of Lrp6-mediated Wnt/beta-catenin signaling in the development and intervention of spinal neural tube defects in mice."xsd:string |
| http://purl.uniprot.org/citations/35514236 | http://purl.uniprot.org/core/volume | "15"xsd:string |
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