{"doi":"10.7554/elife.24419.027","title":"Decision letter: O-GlcNAc on NOTCH1 EGF repeats regulates ligand-induced Notch signaling and vascular development in mammals","abstract":null,"journal":null,"year":2017,"id":671413,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Decision letter: O-GlcNAc on NOTCH1 EGF repeats regulates ligand-induced Notch signaling and vascular development in mammals","abstract":"As an embryo develops, its cells undergo a series of divisions and transformations until they specialize to form distinct cell types. These transformations are regulated by many molecules and signaling pathways. Often one cell will release signaling molecules that are then recognized by specialized receptor proteins on other cells that then trigger a reaction in the receiving cell. A signaling molecule that binds to a receptor is often referred to as a ligand. Specific chains of sugar molecules known as glycans are attached to receptor proteins and help to regulate the signaling pathways that control how cells develop in an embryo. One of these receptors is called the Notch receptor, which carries several types of glycans. Mutations that prevent the glycans from being attached to this receptor can lead to congenital diseases. For example, EOGT is an enzyme that attaches a sugar molecule onto the Notch receptor, and mutations in the gene that encodes EOGT are found in people with Adams-Oliver syndrome – a rare condition that causes their skin and limbs to fail to develop properly. However, it was not clear what exact role the attachment of the sugar molecule (referred to as O-GlcNAc) plays and if it regulates Notch signaling. Sawaguchi et al. studied animal cells grown in the laboratory to investigate ligand binding to Notch receptors and Notch signaling. The experiments showed that if the gene for the EOGT enzyme was deleted, some ligand molecules could not bind well to the Notch signaling receptor. This affected how the receptor became activated and how it triggered a signaling reaction in the receiving cell. In mutant mice that lacked EOGT, the blood vessels of the developing retina had reduced Notch signaling. Blood vessels are important for the normal development of the retina. Together, the results suggest that O-GlcNAc on Notch receptors are important for specific aspects of Notch signaling, including the signals that lead to the normal development of retinal blood vessels. A next step will be to identify other roles of the O-GlcNAc glycans on Notch receptors and to explore how they affect Notch signaling during development. A better understanding of these mechanisms will extend our knowledge of Adams-Oliver syndrome, which at the moment remains a poorly understood condition.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19965766","pmcid":null,"openalex_id":"https://openalex.org/W4235324981","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.7554/elife.24419.027","host_type":""},{"url":"https://doi.org/10.7554/elife.24419.027","host_type":""}],"fields_of_study":["Glycosylation and Glycoproteins Research","Carbohydrate Chemistry and Synthesis","Protein Tyrosine Phosphatases"],"mesh_terms":[],"keywords":["Notch signaling pathway","JAG1","Notch proteins","Hes3 signaling axis","EGF-like domain","Biology","Angiogenesis","Cell biology","Signal transduction","Receptor","Notch 1","Cell signaling","Ligand (biochemistry)","Genetics","Gene","Protein domain"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T02:36:31.415471Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}