title: NBCe1 (SLC4A4) a potential pH regulator in enamel organ cells during enamel development in the mouse.
abstract: During the formation of dental enamel, maturation-stage ameloblasts express ion-transporting transmembrane proteins. The SLC4 family of ion-transporters regulates intra- and extracellular pH in eukaryotic cells by cotransporting HCO3 (-) with Na(+). Mutation in SLC4A4 (coding for the sodium-bicarbonate cotransporter NBCe1) induces developmental defects in human and murine enamel. We have hypothesized that NBCe1 in dental epithelium is engaged in neutralizing protons released during crystal formation in the enamel space. We immunolocalized NBCe1 protein in wild-type dental epithelium and examined the effect of the NBCe1-null mutation on enamel formation in mice. Ameloblasts expressed gene transcripts for NBCe1 isoforms B/D/C/E. In wild-type mice, weak to moderate immunostaining for NBCe1 with antibodies that recognized isoforms A/B/D/E and isoform C was seen in ameloblasts at the secretory stage, with no or low staining in the early maturation stage but moderate to high staining in the late maturation stage. The papillary layer showed the opposite pattern being immunostained prominently at the early maturation stage but with gradually less staining at the mid- and late maturation stages. In NBCe1 (-/-) mice, the ameloblasts were disorganized, the enamel being thin and severely hypomineralized. Enamel organs of CFTR (-/-) and AE2a,b (-/-) mice (CFTR and AE2 are believed to be pH regulators in ameloblasts) contained higher levels of NBCe1 protein than wild-type mice. Thus, the expression of NBCe1 in ameloblasts and the papillary layer cell depends on the developmental stage and possibly responds to pH changes.
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry at Amsterdam (ACTA), Vrije Universiteit, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, The Netherlands, r.jalali@acta.nl.
authors.forename: R
authors.initials: R
authors.lastname: Jalali
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: B
authors.initials: B
authors.lastname: Zandieh-Doulabi
authors.forename: T J M
authors.initials: TJ
authors.lastname: Bervoets
authors.forename: M L
authors.initials: ML
authors.lastname: Paine
authors.forename: W F
authors.initials: WF
authors.lastname: Boron
authors.forename: M D
authors.initials: MD
authors.lastname: Parker
authors.forename: M J C
authors.initials: MJ
authors.lastname: Bijvelds
authors.forename: J F
authors.initials: JF
authors.lastname: Medina
authors.forename: P K
authors.initials: PK
authors.lastname: DenBesten
authors.forename: A L J J
authors.initials: AL
authors.lastname: Bronckers
mesh_terms: D000565:Ameloblasts / Q000166:cytology / Q000378:metabolism; D000566:Amelogenesis; D000818:Animals; D015153:Blotting, Western; D002113:Calcification, Physiologic / Q000235:genetics; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism; D006224:Cricetinae; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004658:Enamel Organ / Q000166:cytology* / Q000000981:diagnostic imaging / Q000196:embryology* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007180:Incisor / Q000378:metabolism; D008334:Mandible / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D027982:Sodium-Bicarbonate Symporters / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D055114:X-Ray Microtomography
chemical_list: D027963:Chloride-Bicarbonate Antiporters; D012333:RNA, Messenger; C498899:Slc4a4 protein, mouse; D027982:Sodium-Bicarbonate Symporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator