{"doi":"10.1101/2025.10.23.684245","title":"Endothelin 3 and T-type Ca\n                  <sup>2+</sup>\n                  channels drive enteric neural crest cell calcium activity, contractility and migration","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Enteric neural crest cells (ENCCs) colonize the gut during embryogenesis and migration defects give rise to Hirschsprung disease (HD). Mutations in GDNF/RET and EDN3/EDNRB are known to be causal in HD. Here, we show that migrating ENCCs in mice exhibit endogenous EDN3/EDNRB-gated calcium activity, mediated by chloride channels, T-type Ca\n                  <jats:sup>2+</jats:sup>\n                  channels and inositol trisphosphate-sensitive intracellular-store release. We find that inhibiting Ca\n                  <jats:sup>2+</jats:sup>\n                  activity results in ENCC migration defects, while exciting it promotes migration by increasing ENCC contractility and traction force to the extracellular matrix. Our study demonstrates that embryonic endothelin-mediated neural crest migration and adult endothelin-mediated vasoconstriction is one and the same phenomenon, taking place in different cell types. Our results suggest a functional link between rare mutations of\n                  <jats:italic>CACNA1H</jats:italic>\n                  (the gene encoding CaV3.2) and HD, and pave the way for understanding neurocristopathies in terms of neural crest cell bioelectric activity deficits.\n                </jats:p>","journal":null,"year":null,"id":670759,"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":[{"id":1752195,"name":"Fanny Gayda","orcid":null,"position":1,"is_corresponding":false},{"id":1752197,"name":"Nadège Bondurand","orcid":null,"position":2,"is_corresponding":false},{"id":1752199,"name":"Zechi Chan","orcid":null,"position":3,"is_corresponding":false},{"id":826531,"name":"Thierry Savy","orcid":"0000-0001-5970-3817","position":4,"is_corresponding":false},{"id":1752202,"name":"Monique Frain","orcid":null,"position":5,"is_corresponding":false},{"id":1752203,"name":"Amira El Merhie","orcid":"0000-0001-6580-9677","position":6,"is_corresponding":false},{"id":1752204,"name":"Lenuta Canta","orcid":null,"position":7,"is_corresponding":false},{"id":1752205,"name":"Monica Dicu","orcid":null,"position":8,"is_corresponding":false},{"id":1752206,"name":"Isabelle Le Parco","orcid":null,"position":9,"is_corresponding":false},{"id":1752207,"name":"Léna Zig","orcid":null,"position":10,"is_corresponding":false},{"id":1752194,"name":"Nicolas R. Chevalier","orcid":"0000-0002-9713-1511","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Endothelin 3 and T-type Ca\n                  <sup>2+</sup>\n                  channels drive enteric neural crest cell calcium activity, contractility and migration","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Enteric neural crest cells (ENCCs) colonize the gut during embryogenesis and migration defects give rise to Hirschsprung disease (HD). Mutations in GDNF/RET and EDN3/EDNRB are known to be causal in HD. Here, we show that migrating ENCCs in mice exhibit endogenous EDN3/EDNRB-gated calcium activity, mediated by chloride channels, T-type Ca\n                  <jats:sup>2+</jats:sup>\n                  channels and inositol trisphosphate-sensitive intracellular-store release. We find that inhibiting Ca\n                  <jats:sup>2+</jats:sup>\n                  activity results in ENCC migration defects, while exciting it promotes migration by increasing ENCC contractility and traction force to the extracellular matrix. Our study demonstrates that embryonic endothelin-mediated neural crest migration and adult endothelin-mediated vasoconstriction is one and the same phenomenon, taking place in different cell types. Our results suggest a functional link between rare mutations of\n                  <jats:italic>CACNA1H</jats:italic>\n                  (the gene encoding CaV3.2) and HD, and pave the way for understanding neurocristopathies in terms of neural crest cell bioelectric activity deficits.\n                </jats:p>","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":"19162232","pmcid":null,"openalex_id":"https://openalex.org/W4415503179","authors":[],"funders":[{"funder_name":"","grant_id":"CHEVA19RDX-MEUP1","title":null},{"funder_name":"Centre National de la Recherche Scientifique","grant_id":"PEPS INSIS COXHAM","title":null},{"funder_name":"French National Research Agency (ANR)","grant_id":"ANR-11-LABX-0071","title":null}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"https://www.biorxiv.org/about/FAQ#license","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2025/10/24/2025.10.23.684245.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2025/10/24/2025.10.23.684245.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2025.10.23.684245","host_type":"publisher"},{"url":"https://doi.org/10.1101/2025.10.23.684245","host_type":"repository"},{"url":"https://hal.science/hal-05390884","host_type":"repository"},{"url":"https://doi.org/10.1038/s41467-025-68121-5","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/41559055","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/41559055/","host_type":""},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12876838/","host_type":""},{"url":"https://u-paris.hal.science/hal-05648911v1","host_type":""}],"fields_of_study":["Congenital gastrointestinal and neural anomalies","Gastrointestinal motility and disorders","0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["Neural crest","Contractility","Cell migration","Extracellular","Calcium","Crest","Cell","Vasoconstriction","Enteric nervous system","Extracellular matrix","Endothelin-3","Receptor, Endothelin B","Article","[SDV] Life Sciences [q-bio]","Calcium Channels, T-Type","Mice","Cell Movement","Mutation","Animals","Hirschsprung Disease"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-15T23:41:37.466466Z","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":[]}