NBCe1 (SLC4A4) a potential pH regulator in enamel organ cells during enamel development in the mouse
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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.
KeywordsTooth development Enamel pH regulation Mineralization Sodium-bicarbonate cotransporter 1 (NBCe1) Cystic fibrosis transmembrane conductance regulator (CFTR) Anion exchanger-2 (AE2) Rodents
The authors thank Dr. H. de Jonge (Erasmus University, Rotterdam, The Netherlands) and Dr. J. Bolscher (Department of Oral Biochemistry, ACTA, Amsterdam, The Netherlands) for advice. The authors are also grateful to Dr. Gary E. Shull (Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA) for providing breeding pairs of the NBCe1+/− animals. Currently, these mice are available from the Mutant Mice Regional Resource Center (MMRRC), stock no. 034263-JAX.
- Bronckers AL, Lyaruu DM, Jansen ID, Medina JF, Kellokumpu S, Hoeben KA, Gawenis LR, Oude-Elferink RP, Everts V (2009) Localization and function of the anion exchanger Ae2 in developing teeth and orofacial bone in rodents. J Exp Zool B Mol Dev Evol 312B:375–387PubMedCrossRefPubMedCentralGoogle Scholar
- Bronckers A, Kalogeraki L, Jorna HJ, Wilke M, Bervoets TJ, Lyaruu DM, Zandieh-Doulabi B, DenBesten P, de Jonge H (2010) The cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in maturation stage ameloblasts, odontoblasts and bone cells. Bone 46:1188–1196PubMedCrossRefPubMedCentralGoogle Scholar
- Bronckers AL, Guo J, Zandieh-Doulabi B, Bervoets TJ, Lyaruu DM, Li X, Wangemann P, DenBesten P (2011) Developmental expression of solute carrier family 26A member 4 (SLC26A4/pendrin) during amelogenesis in developing rodent teeth. Eur J Oral Sci 119 (Suppl 1):185–192PubMedCrossRefPubMedCentralGoogle Scholar