title: Orai1 expression pattern in tooth and craniofacial ectodermal tissues and potential functions during ameloblast differentiation.
abstract: BACKGROUND
  Orai1 is a plasma membrane protein that forms the pore of the calcium release activated calcium channel. Humans with mutated Orai1 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 Orai1 deficient patients. The expression pattern and potential functions of Orai1 in enamel formation remains unclear. To contribute toward understanding the role of Orai1 in amelogenesis we characterized ORAI1 protein developmental pattern in comparison with other ectodermal organs. We also examined the effects of Orai1 down-regulation in ameloblast cell proliferation and differentiation.
  
  
  RESULTS
  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 Orai1 expression decreases cell proliferation and results in RNA expression levels changes of key ameloblast genes regulating enamel thickness and mineralization.
  
  
  CONCLUSIONS
  This study provides insights in the anhidrotic ectodermal dysplasia phenotype due to Orai1 mutation and highlights the importance of calcium signaling in controlling ameloblast differentiation and maturation during tooth development.
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, Michigan.|Department of Otolaryngology, School of Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Vina
authors.initials: V
authors.lastname: Zinn
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Anna
authors.initials: A
authors.lastname: Lefkelidou
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Nawar
authors.initials: N
authors.lastname: Taqi
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Xanthippi
authors.initials: X
authors.lastname: Chatzistavrou
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Tarek
authors.initials: T
authors.lastname: Balam
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Nervina
authors.affiliation: Department of Otolaryngology, School of Medicine, University of Michigan, Ann Arbor, Michigan.|Department of Periodontology and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Silvana
authors.initials: S
authors.lastname: Papagerakis
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, Michigan.|Center for Organogenesis, School of Medicine, University of Michigan, Ann Arbor, Michigan.|Center for Computational Medicine and Bioinformatics, School of Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Petros
authors.initials: P
authors.lastname: Papagerakis
mesh_terms: D000565:Ameloblasts / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D002454:Cell Differentiation; D049109:Cell Proliferation; D004476:Ectodermal Dysplasia / Q000235:genetics; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D018859:Hair Follicle / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009061:Mouth Mucosa / Q000378:metabolism; D000071740:ORAI1 Protein; D000071741:ORAI2 Protein; D038081:Organogenesis; D012469:Salivary Glands / Q000378:metabolism; D014070:Tooth / Q000196:embryology* / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; D000071741:ORAI2 Protein; C520430:Orai1 protein, mouse; C520431:Orai2 protein, mouse
keywords: amelogenesis imperfect; calcium channels; dentin; ectodermal dysplasia; enamel; hair follicle; oral epithelium; salivary glands