{"doi":"10.14293/cgmp.24000069.v1","title":"Cytoglobin regulates NO-dependent cilia motility and organ laterality during development","abstract":"<p class=\"first\" dir=\"auto\" id=\"d1589659e274\">Cytoglobin is a highly conserved redox sensor heme protein with unknown physiological function. Unexpectedly, genetic deletion of zebrafish cytoglobin ( <i>cygb2</i>) causes cardiac laterality defects showing an abnormal opposite left-right orientation of the heart. In humans, cardiac laterality determination is dependent on motile cilia function. Importantly, primary ciliary dyskinesia (PCD) is associated with low nitric oxide (NO) levels in airway epithelial cells. Using the zebrafish model we found that Cygb2 co-localized with cilia and the NO synthase Nos2b in the embryonic laterality organ and the structure and function of cilia were disrupted in <i>cygb2</i> mutants. In addition, we detected lower levels of cGMP in mutants. Abnormal ciliary function and organ laterality defects were phenocopied by depletion of <i>nos2b</i> and <i>gucy1a</i>, the canonical NO receptor soluble guanylate cyclase (sGC) homolog in fish, and rescued by exposing <i>cygb2</i> mutant embryos to an NO donor or an sGC stimulator and with over-expression of <i>nos2b</i>. Consistent with a conserved role in the modulation of ciliary function, cytoglobin knock out in the mouse also impaired airway epithelial ciliary structure and beat frequency. This is the first evidence that cytoglobin is essential for normal developmental stage-specific NO signaling, ciliogenesis and cilia motility, required for the establishment of left-right patterning.","journal":null,"year":2024,"id":498256,"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":0.9588,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":524699,"name":"Jianmin Xue","orcid":null,"position":1,"is_corresponding":false},{"id":1100137,"name":"Manush Sayd Mohammed","orcid":null,"position":2,"is_corresponding":false},{"id":517817,"name":"Caroline Smith","orcid":"0000-0002-9154-6855","position":3,"is_corresponding":false},{"id":1099702,"name":"Anders Hay‐Schmidt","orcid":"0000-0001-9984-7014","position":4,"is_corresponding":false},{"id":1345061,"name":"Antony DeMartino","orcid":null,"position":5,"is_corresponding":false},{"id":517349,"name":"Adam Clark","orcid":"0000-0003-4090-7232","position":6,"is_corresponding":false},{"id":526580,"name":"Qinzi Xu","orcid":"0000-0002-3149-5777","position":7,"is_corresponding":false},{"id":314377,"name":"Cecilia Lo","orcid":"0000-0003-4314-3434","position":8,"is_corresponding":false},{"id":264202,"name":"Michael Tsang","orcid":"0000-0001-7123-0063","position":9,"is_corresponding":false},{"id":347796,"name":"Jesús Tejero","orcid":"0000-0003-3245-9978","position":10,"is_corresponding":false},{"id":24963,"name":"Mark T. Gladwin","orcid":"0000-0001-7267-9006","position":11,"is_corresponding":false},{"id":1099703,"name":"Paola Corti","orcid":"0000-0002-3397-0041","position":12,"is_corresponding":false},{"id":634818,"name":"Elizabeth Rochon","orcid":"0000-0001-5521-0513","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:09:38.543544Z","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":[]}