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Cell and Tissue Research

, Volume 358, Issue 2, pp 433–442 | Cite as

NBCe1 (SLC4A4) a potential pH regulator in enamel organ cells during enamel development in the mouse

  • R. Jalali
  • J. Guo
  • B. Zandieh-Doulabi
  • T. J. M. Bervoets
  • M. L. Paine
  • W. F. Boron
  • M. D. Parker
  • M. J. C. Bijvelds
  • J. F. Medina
  • P. K. DenBesten
  • A. L. J. J. Bronckers
Regular article

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.

Keywords

Tooth development Enamel pH regulation Mineralization Sodium-bicarbonate cotransporter 1 (NBCe1) Cystic fibrosis transmembrane conductance regulator (CFTR) Anion exchanger-2 (AE2) Rodents 

Notes

Acknowledgments

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.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • R. Jalali
    • 1
    • 2
  • J. Guo
    • 1
    • 2
  • B. Zandieh-Doulabi
    • 1
    • 2
  • T. J. M. Bervoets
    • 1
    • 2
  • M. L. Paine
    • 3
  • W. F. Boron
    • 4
  • M. D. Parker
    • 4
  • M. J. C. Bijvelds
    • 5
  • J. F. Medina
    • 6
  • P. K. DenBesten
    • 7
  • A. L. J. J. Bronckers
    • 1
    • 2
  1. 1.Department of Oral Cell Biology, Academic Centre for Dentistry at Amsterdam (ACTA)Vrije UniversiteitAmsterdamThe Netherlands
  2. 2.VU University Amsterdam, MOVE Research InstituteAmsterdamThe Netherlands
  3. 3.Centre for Craniofacial Molecular BiologyHerman Ostrow School of Dentistry Los AngelesLos AngelesUSA
  4. 4.Department of Physiology and BiophysicsCase Western Reserve University, School of Medical SciencesClevelandUSA
  5. 5.Department of Gastroenterology and HepatologyErasmus University Medical Center RotterdamRotterdamThe Netherlands
  6. 6.Division of Gene Therapy and Hepatology, School of Medicine/CIMAUniversity of NavarraPamplonaSpain
  7. 7.Department of Oral SciencesUniversity of California in San FranciscoSan FranciscoUSA

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