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We further show that Cadherin-16 regulates whole-body calcium and ultimately behavior through the hormone Stanniocalcin 1l (Stc1l), and the IGF-regulatory metalloprotease, Papp-aa. Finally, we demonstrate the importance of the CS through ablation experiments that reveal its role in promoting normal acoustic sensory gating. Together, our results uncover a previously undescribed brain non-autonomous pathway for the regulation of behavior and underscore Ca<jats:sup>2+</jats:sup> homeostasis as a critical process underlying sensory gating <jats:italic>in vivo.</jats:italic></jats:p>","journal":"PLOS Biology","year":2025,"id":688750,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"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":[{"id":1799348,"name":"Zackary Q. 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Despite the importance of sensory thresholds for animal behavior and human health, we do not yet have a full appreciation of the underlying molecular-genetic and circuit mechanisms. The larval zebrafish acoustic startle response provides a powerful system to identify molecular mechanisms underlying establishment of sensory thresholds and plasticity of thresholds through mechanisms like habituation. Using this system, we identify Cadherin-16 as a previously undescribed regulator of sensory gating. We demonstrate that Cadherin-16 regulates sensory thresholds via an endocrine organ, the corpuscle of Stannius (CS), which is essential in zebrafish for regulating Ca<jats:sup>2+</jats:sup> homeostasis. We further show that Cadherin-16 regulates whole-body calcium and ultimately behavior through the hormone Stanniocalcin 1l (Stc1l), and the IGF-regulatory metalloprotease, Papp-aa. Finally, we demonstrate the importance of the CS through ablation experiments that reveal its role in promoting normal acoustic sensory gating. Together, our results uncover a previously undescribed brain non-autonomous pathway for the regulation of behavior and underscore Ca<jats:sup>2+</jats:sup> homeostasis as a critical process underlying sensory gating <jats:italic>in vivo.</jats:italic></jats:p>","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40315416","pmcid":"PMC12077787","openalex_id":"https://openalex.org/W4410025815","authors":[],"funders":[{"funder_name":"Boettcher Foundation","grant_id":"na","title":null},{"funder_name":"National Institute of Neurological Disorders and Stroke","grant_id":"R00NS111736","title":null},{"funder_name":"National Institute of General Medical Sciences","grant_id":"T32GM141742","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK116073","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"P30 NS048154","title":null},{"funder_name":"National Institutes of Health","grant_id":"3T32GM141742-04S1","title":"Predoctoral Training in the Genetics of Development, Disease and Regeneration"},{"funder_name":"National Institutes of Health","grant_id":"4R00NS111736-03","title":"Understanding how post-translational palmitoylation influences in vivo molecular and circuit dynamics during learning"},{"funder_name":"National Institutes of Health","grant_id":"5P30NS048154-04","title":"MICROSCOPY CORE - ROCKY MOUNTAIN NEUROLOGICAL DISORDERS CORE CENTER"},{"funder_name":"National Institutes of Health","grant_id":"5P30DK116073-03","title":"UC Denver Diabetes Research Center"},{"funder_name":"National Science Foundation","grant_id":"2322260","title":"CC* Regional Computing: Enhancing Computing At Regional Schools in the Rocky Mountain Advanced Computing Consortium (RMACC)"},{"funder_name":"National Science Foundation","grant_id":"2201538","title":"CC* Compute: HPC Services for the Colorado State University System"}],"total_grants":11,"fwci":5.3604,"citation_percentile":0.95298381,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":5}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3003164&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3003164&type=printable","host_type":"publisher"},{"url":"https://dx.plos.org/10.1371/journal.pbio.3003164","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pbio.3003164","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40315416","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12077787","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12077787","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12077787?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pbio.3003164","host_type":""}],"fields_of_study":["Marine animal studies overview","Hearing, Cochlea, Tinnitus, Genetics","Zebrafish Biomedical Research Applications","Animals","Zebrafish","Cadherins","Zebrafish Proteins","Calcium","Sensory Gating","Signal Transduction","Reflex, Startle","Homeostasis","Larva"],"mesh_terms":["Animals","Calcium","Homeostasis","Larva","Reflex, Startle","Zebrafish","Signal Transduction","Cadherins","Zebrafish Proteins","Sensory Gating"],"keywords":["Zebrafish","Biology","Sensory system","Neuroscience","Gating","Habituation","Sensory gating","Sensory neuron","Calcium imaging","Internal medicine","Genetics","Calcium","Gene","Reflex, Startle","Larva","Animals","Homeostasis","Zebrafish Proteins","Cadherins","Research Article","Signal Transduction"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-19T18:56:46.105626Z","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":[]}