{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:19:41Z","timestamp":1777652381402,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R21DE026861"],"award-info":[{"award-number":["R21DE026861"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["5R01DE031044"],"award-info":[{"award-number":["5R01DE031044"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1S10OD023440"],"award-info":[{"award-number":["1S10OD023440"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Ionocytes are distinct epithelial sensory cells scattered throughout the ductal system of the salivary glands. These cells are distinguished by their unusual morphology, as well as by a specific transcriptomic signature that includes the expression of the forkhead boxI1 (Foxi1) and achaete scute\u2010like 3 (Ascl3) transcription factors. Currently little is known about the biology or function of ionocytes in the salivary glands. To facilitate the characterization of these cells, we produced an inducible Cre mouse allele driven by the\n                      <jats:italic>Ascl3<\/jats:italic>\n                      promoter. This strain was crossed with a reporter to fluorescently label Ascl3\n                      <jats:sup>+<\/jats:sup>\n                      ionocytes, highlighting that they are the site of enriched cystic fibrosis transmembrane conductance regulator (Cftr) expression in the salivary glands and demonstrating the proximity of these cells to neurons. Conditional Cre\u2010mediated cell ablation, using diphtheria toxin (DTA), removed Ascl3\n                      <jats:sup>+<\/jats:sup>\n                      ionocytes from the salivary glands and resulted in an altered pH of total saliva, supporting a function for ionocytes in transepithelial ion flow. Finally Cre\u2010mediated expression of the calcium indicator GCaMP6f revealed thatAscl3\n                      <jats:sup>+<\/jats:sup>\n                      ionocytes exhibit unique properties not observed in the acinar or surrounding duct cells, including elevated basal [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:italic>\n                        <jats:sub>i<\/jats:sub>\n                      <\/jats:italic>\n                      , spontaneous blinking in the absence of stimulation and a rapid loss of [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      after nerve stimulation. These unique properties distinguish ionocytes as a specialized subset of salivary gland duct cells.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70378-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Ionocytes are epithelial cells originally identified in marine teleosts and subsequently reported to be present in pulmonary epithelia, olfactory epithelium and salivary and lachrimal glands.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            We produced an inducible Cre mouse allele driven by the\n                            <jats:italic>Ascl3<\/jats:italic>\n                            promoter to study the distribution and function of Ascl3\n                            <jats:sup>+<\/jats:sup>\n                            ionocytes in salivary glands.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            By crossing this strain with a fluorescent reporter, we demonstrated the prominent localization of Ascl3\n                            <jats:sup>+<\/jats:sup>\n                            ionocytes in salivary gland ducts.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Cre\u2010mediated expression of the genetically encoded Ca\n                            <jats:sup>2+<\/jats:sup>\n                            indicator GCamp6f in Ascl3\n                            <jats:sup>+<\/jats:sup>\n                            ionocytes revealed unique Ca\n                            <jats:sup>2+<\/jats:sup>\n                            signalling properties of this cell type distinct from acinar cells and other ductal cell types.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Cre\u2010mediated ablation of Ascl3\n                            <jats:sup>+<\/jats:sup>\n                            ionocytes altered the pH of the final saliva.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We conclude that ionocytes resident in salivary gland ducts function to modify the primary saliva contributing to the composition of the final saliva entering the oral cavity.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp290098","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T05:24:56Z","timestamp":1771651496000},"page":"2642-2658","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ascl3\n                    <sup>+<\/sup>\n                    ionocytes in murine salivary gland ducts are innervated sensory cells that display unique calcium signalling characteristics and contribute to the composition of saliva"],"prefix":"10.1113","volume":"604","author":[{"given":"Hitoshi","family":"Uchida","sequence":"first","affiliation":[{"name":"Center for Oral Biology University of Rochester School of Medicine  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eri O.","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Center for Oral Biology University of Rochester School of Medicine  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Takano","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology University of Rochester School of Medicine  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marit H.","family":"Aure","sequence":"additional","affiliation":[{"name":"Center for Oral Biology University of Rochester School of Medicine  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa F.","family":"Glasner","sequence":"additional","affiliation":[{"name":"Center for Oral Biology University of Rochester School of Medicine  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zamira Guerra","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Biomedical Genetics University of Rochester School of Medicine  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta C.","family":"Faustoferri","sequence":"additional","affiliation":[{"name":"Center for Oral Biology University of Rochester School of Medicine  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. 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