{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:22:29Z","timestamp":1783444949937,"version":"3.54.6"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,8,12]],"date-time":"2015-08-12T00:00:00Z","timestamp":1439337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"American Association of Orthodontists Foundation (AAOF)","award":["N017774-00"],"award-info":[{"award-number":["N017774-00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p><jats:bold><jats:styled-content>Background:<\/jats:styled-content><\/jats:bold> <jats:italic>Orai1<\/jats:italic> is a plasma membrane protein that forms the pore of the calcium release activated calcium channel. Humans with mutated <jats:italic>Orai1<\/jats:italic> present with hereditary combined immunodeficiency, congenital myopathy and anhidrotic ectodermal dysplasia. Consistent with the ectodermal dysplasia phenotype, enamel formation and mineralization is also abnormal in <jats:italic>Orai1<\/jats:italic> deficient patients. The expression pattern and potential functions of <jats:italic>Orai1<\/jats:italic> in enamel formation remains unclear. To contribute toward understanding the role of <jats:italic>Orai1<\/jats:italic> in amelogenesis we characterized ORAI1 protein developmental pattern in comparison with other ectodermal organs. We also examined the effects of <jats:italic>Orai1<\/jats:italic> down\u2010regulation in ameloblast cell proliferation and differentiation. <jats:bold><jats:styled-content>Results:<\/jats:styled-content><\/jats:bold> Our data show strong expression of ORAI1 protein during the ameloblast secretory stage, which weans at the end of the maturation stage. In salivary glands, ORAI1 is expressed mainly in acini cells. ORAI1 expression is also found in hair follicle and oral epithelium. Knockdown of <jats:italic>Orai1<\/jats:italic> expression decreases cell proliferation and results in RNA expression levels changes of key ameloblast genes regulating enamel thickness and mineralization. <jats:bold><jats:styled-content>Conclusions:<\/jats:styled-content><\/jats:bold> This study provides insights in the anhidrotic ectodermal dysplasia phenotype due to <jats:italic>Orai1<\/jats:italic> mutation and highlights the importance of calcium signaling in controlling ameloblast differentiation and maturation during tooth development. <jats:italic>Developmental Dynamics 244:1249\u20131258, 2015<\/jats:italic>. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.24307","type":"journal-article","created":{"date-parts":[[2015,7,15]],"date-time":"2015-07-15T09:55:34Z","timestamp":1436954134000},"page":"1249-1258","source":"Crossref","is-referenced-by-count":16,"title":["Orai1 expression pattern in tooth and craniofacial ectodermal tissues and potential functions during ameloblast differentiation"],"prefix":"10.1002","volume":"244","author":[{"given":"Li","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry School of Dentistry, University of Michigan Ann Arbor Michigan"},{"name":"Department of Otolaryngology School of Medicine, University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vina","family":"Zinn","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry School of Dentistry, University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lefkelidou","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry School of Dentistry, University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawar","family":"Taqi","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry School of Dentistry, University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xanthippi","family":"Chatzistavrou","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry School of Dentistry, University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek","family":"Balam","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry School of Dentistry, University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Nervina","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry School of Dentistry, University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Papagerakis","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology School of Medicine, University of Michigan Ann Arbor Michigan"},{"name":"Department of Periodontology and Oral Medicine School of Dentistry, University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petros","family":"Papagerakis","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry School of Dentistry, University of Michigan Ann Arbor Michigan"},{"name":"Center for Organogenesis School of Medicine, University of Michigan Ann Arbor Michigan"},{"name":"Center for Computational Medicine and Bioinformatics School of Medicine, University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,8,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00283.2009"},{"key":"e_1_2_6_3_1","first-page":"7","article-title":"Oligodontia ectodermal dysplasia\u2013on signs, symptoms, genetics, and outcomes of dental treatment","volume":"13","author":"Bergendal B.","year":"2010","journal-title":"Swed Dent J 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