{"doi":"10.1101/2021.05.06.442974","title":"Endothelial Unc5B controls blood-brain barrier integrity","abstract":"Abstract Blood-brain barrier (BBB) integrity is critical for proper function of the central nervous system (CNS). Here, we showed that the endothelial Netrin1 receptor Unc5B controls BBB integrity by maintaining Wnt/β–catenin signaling. Inducible endothelial-specific deletion of Unc5B in adult mice led to region and size-selective BBB opening. Loss of Unc5B decreased BBB Wnt/β–catenin signaling, and β–catenin overexpression rescued Unc5B mutant BBB defects. Mechanistically, Netrin1 enhanced Unc5B interaction with the Wnt co-receptor LRP6, induced its phosphorylation and activated Wnt/β–catenin downstream signaling. Intravenous delivery of antibodies blocking Netrin1 binding to Unc5B caused a transient disruption of Wnt signaling and BBB breakdown, followed by neurovascular barrier resealing. These data identify Netrin-Unc5B signaling as a novel regulator of BBB integrity with potential therapeutic utility for CNS diseases.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":214773,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":727308,"name":"Luiz Henrique Geraldo","orcid":"0000-0003-3318-4697","position":1,"is_corresponding":false},{"id":808794,"name":"Jessica Furtado","orcid":"0000-0002-7975-2592","position":2,"is_corresponding":false},{"id":808795,"name":"Laurence Pibouin-Fragner","orcid":"0000-0001-5771-3958","position":3,"is_corresponding":false},{"id":558825,"name":"Mathilde Poulet","orcid":"0000-0002-2216-4132","position":4,"is_corresponding":false},{"id":571900,"name":"Doyeun Kim","orcid":null,"position":5,"is_corresponding":false},{"id":608582,"name":"Bryce Nelson","orcid":null,"position":6,"is_corresponding":false},{"id":808796,"name":"Yunling Xu","orcid":"0000-0002-8225-2206","position":7,"is_corresponding":false},{"id":808797,"name":"Laurent Jacob","orcid":"0000-0003-4767-0442","position":8,"is_corresponding":false},{"id":808798,"name":"Nawal Maïssa","orcid":"0000-0002-7133-7220","position":9,"is_corresponding":false},{"id":260726,"name":"Bertrand Tavitian","orcid":"0000-0002-5349-8194","position":10,"is_corresponding":false},{"id":260207,"name":"Dritan Agalliu","orcid":"0000-0002-5375-4143","position":11,"is_corresponding":false},{"id":110372,"name":"Lena Claesson‐Welsh","orcid":"0000-0003-4275-2000","position":12,"is_corresponding":false},{"id":300751,"name":"Susan L. Ackerman","orcid":"0000-0002-6740-593X","position":13,"is_corresponding":false},{"id":260725,"name":"Anne Eichmann","orcid":"0000-0001-5563-210X","position":14,"is_corresponding":false},{"id":808793,"name":"Kevin Boyé","orcid":"0000-0002-5749-959X","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:52:51.201033Z","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":[]}