Skip to main content

Advertisement

SpringerLink
Log in

Expression patterns of WNT/β-CATENIN signaling molecules during human tooth development

  • Original Paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

The WNT/β-CATENIN signaling has been demonstrated to play critical roles in mouse tooth development, but little is known about the status of these molecules in human embryonic tooth. In this study, expression patterns of WNT/β-CATENIN signaling components, including WNT ligands (WNT3, WNT5A), receptors (FZD4, FZD6, LRP5), transducers (β-CATENIN), transcription factors (TCF4, LEF1) and antagonists (DKK1, SOSTDC1) were investigated in human tooth germ at the bud, cap and bell stages by in situ hybridization. All these genes exhibited similar but slightly distinct expression patterns in human tooth germ in comparison with mouse. Furthermore the mRNA expression of these genes in incisors and molars at the bell stage was also examined by real-time PCR. Our results reveal the status of active WNT/β-CATENIN signaling in the human tooth germ and suggest these components may also play an essential role in the regulation of human tooth development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Adaimy L, Chouery E, Megarbane H, Mroueh S, Delague V, Nicolas E, Belguith H, de Mazancourt P, Megarbane A (2007) Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. Am J Hum Genet 81(4):821–828

    Article  PubMed Central  PubMed  Google Scholar 

  • Blanton SH, Bertin T, Serna ME, Stal S, Mulliken JB, Hecht JT (2004) Association of chromosomal regions 3p21.2, 10p13, and 16p13.3 with nonsyndromic cleft lip and palate. Am J Med Genet A 125A(1):23–27

    Article  PubMed  Google Scholar 

  • Bohring A, Stamm T, Spaich C, Haase C, Spree K, Hehr U, Hoffmann M, Ledig S, Sel S, Wieacker P, Ropke A (2009) WNT10A mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes. Am J Hum Genet 85(1):97–105

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Daa T, Kashima K, Kaku N, Suzuki M, Yokoyama S (2004) Mutations in components of the Wnt signaling pathway in adenoid cystic carcinoma. Mod Pathol 17(12):1475–1482

    Article  CAS  PubMed  Google Scholar 

  • Daa T, Kaku N, Kashima K, Nakayama I, Yokoyama S (2005) Expression of beta-catenin, E-cadherin and cyclin D1 in adenoid cystic carcinoma of the salivary gland. J Exp Clin Cancer Res 24(1):83–87

    CAS  PubMed  Google Scholar 

  • Du J, Wang Q, Wang L, Wang X, Yang P (2012) The expression pattern of FHL2 during mouse molar development. J Mol Histol 43(3):289–295

    Article  CAS  PubMed  Google Scholar 

  • Feng J, McDaniel JS, Chuang HH, Huang O, Rakian A, Xu X, Steffensen B, Donly KJ, MacDougall M, Chen S (2012) Binding of amelogenin to MMP-9 and their co-expression in developing mouse teeth. J Mol Histol 43(5):473–485

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fjeld K, Kettunen P, Furmanek T, Kvinnsland IH, Luukko K (2005) Dynamic expression of Wnt signaling-related Dickkopf1, -2, and -3 mRNAs in the developing mouse tooth. Dev Dyn 233(1):161–166

    Article  CAS  PubMed  Google Scholar 

  • Foulkes WD (1995) A tale of four syndromes: familial adenomatous polyposis, Gardner syndrome, attenuated APC and Turcot syndrome. QJM 88(12):853–863

    CAS  PubMed  Google Scholar 

  • Frierson HF Jr, El-Naggar AK, Welsh JB, Sapinoso LM, Su AI, Cheng J, Saku T, Moskaluk CA, Hampton GM (2002) Large scale molecular analysis identifies genes with altered expression in salivary adenoid cystic carcinoma. Am J Pathol 161(4):1315–1323

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gary C, Schoenwolf SBB, Brauer PR, Francis-West PH (2008) Larsen’s Human Embryology, 4th edn. Churchill Livingstone, London

    Google Scholar 

  • Hjalt TA, Semina EV, Amendt BA, Murray JC (2000) The Pitx2 protein in mouse development. Dev Dyn 218(1):195–200

    Article  CAS  PubMed  Google Scholar 

  • Hu X, Zhang S, Chen G, Lin C, Huang Z, Chen Y, Zhang Y (2013) Expression of SHH signaling molecules in the developing human primary dentition. BMC Dev Biol 13:11

    Article  PubMed Central  PubMed  Google Scholar 

  • Huelsken J, Behrens J (2002) The Wnt signalling pathway. J Cell Sci 115(Pt 21):3977–3978

    Article  CAS  PubMed  Google Scholar 

  • Itasaki N, Jones CM, Mercurio S, Rowe A, Domingos PM, Smith JC, Krumlauf R (2003) Wise, a context-dependent activator and inhibitor of Wnt signalling. Development 130(18):4295–4305

    Article  CAS  PubMed  Google Scholar 

  • Jarvinen E, Salazar-Ciudad I, Birchmeier W, Taketo MM, Jernvall J, Thesleff I (2006) Continuous tooth generation in mouse is induced by activated epithelial Wnt/beta-catenin signaling. Proc Natl Acad Sci USA 103(49):18627–18632

    Article  PubMed Central  PubMed  Google Scholar 

  • Kassai Y, Munne P, Hotta Y, Penttila E, Kavanagh K, Ohbayashi N, Takada S, Thesleff I, Jernvall J, Itoh N (2005) Regulation of mammalian tooth cusp patterning by ectodin. Science 309(5743):2067–2070

    Article  CAS  PubMed  Google Scholar 

  • Kawabata T, Takahashi K, Sugai M, Murashima-Suginami A, Ando S, Shimizu A, Kosugi S, Sato T, Nishida M, Murakami K, Iizuka T (2005) Polymorphisms in PTCH1 affect the risk of ameloblastoma. J Dent Res 84(9):812–816

    Article  CAS  PubMed  Google Scholar 

  • Kettunen P, Loes S, Furmanek T, Fjeld K, Kvinnsland IH, Behar O, Yagi T, Fujisawa H, Vainio S, Taniguchi M, Luukko K (2005) Coordination of trigeminal axon navigation and patterning with tooth organ formation: epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgfbeta1 regulate semaphorin 3a expression in the dental mesenchyme. Development 132(2):323–334

    Article  CAS  PubMed  Google Scholar 

  • Laurikkala J, Kassai Y, Pakkasjarvi L, Thesleff I, Itoh N (2003) Identification of a secreted BMP antagonist, ectodin, integrating BMP, FGF, and SHH signals from the tooth enamel knot. Dev Biol 264(1):91–105

    Article  CAS  PubMed  Google Scholar 

  • Lei H, Liu H, Ding Y, Ge L (2014) Immunohistochemical localization of Pax6 in the developing tooth germ of mice. J Mol Histol. doi:10.1007/s10735-014-9564-5

  • Lin D, Huang Y, He F, Gu S, Zhang G, Chen Y, Zhang Y (2007) Expression survey of genes critical for tooth development in the human embryonic tooth germ. Dev Dyn 236(5):1307–1312

    Article  CAS  PubMed  Google Scholar 

  • Lin M, Li L, Liu C, Liu H, He F, Yan F, Zhang Y, Chen Y (2011) Wnt5a regulates growth, patterning, and odontoblast differentiation of developing mouse tooth. Dev Dyn 240(2):432–440

    Article  PubMed Central  PubMed  Google Scholar 

  • Liu F, Millar SE (2010) Wnt/beta-catenin signaling in oral tissue development and disease. J Dent Res 89(4):318–330

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu F, Chu EY, Watt B, Zhang Y, Gallant NM, Andl T, Yang SH, Lu MM, Piccolo S, Schmidt-Ullrich R, Taketo MM, Morrisey EE, Atit R, Dlugosz AA, Millar SE (2008) Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis. Dev Biol 313(1):210–224

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mikels AJ, Nusse R (2006a) Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol 4(4):e115

    Article  PubMed Central  PubMed  Google Scholar 

  • Mikels AJ, Nusse R (2006b) Wnts as ligands: processing, secretion and reception. Oncogene 25(57):7461–7468

    Article  CAS  PubMed  Google Scholar 

  • Millar SE, Koyama E, Reddy ST, Andl T, Gaddapara T, Piddington R, Gibson CW (2003) Over- and ectopic expression of Wnt3 causes progressive loss of ameloblasts in postnatal mouse incisor teeth. Connect Tissue Res 44(Suppl 1):124–129

    Article  CAS  PubMed  Google Scholar 

  • Mustonen T, Pispa J, Mikkola ML, Pummila M, Kangas AT, Pakkasjarvi L, Jaatinen R, Thesleff I (2003) Stimulation of ectodermal organ development by Ectodysplasin-A1. Dev Biol 259(1):123–136

    Article  CAS  PubMed  Google Scholar 

  • Niemann S, Zhao C, Pascu F, Stahl U, Aulepp U, Niswander L, Weber JL, Muller U (2004) Homozygous WNT3 mutation causes tetra-amelia in a large consanguineous family. Am J Hum Genet 74(3):558–563

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Peng L, Dong G, Xu P, Ren LB, Wang CL, Aragon M, Zhou XD, Ye L (2010a) Expression of Wnt5a in tooth germs and the related signal transduction analysis. Arch Oral Biol 55(2):108–114

    Article  CAS  PubMed  Google Scholar 

  • Peng L, Ren LB, Dong G, Wang CL, Xu P, Ye L, Zhou XD (2010b) Wnt5a promotes differentiation of human dental papilla cells. Int Endod J 43(5):404–412

    Article  CAS  PubMed  Google Scholar 

  • Pispa J, Mustonen T, Mikkola ML, Kangas AT, Koppinen P, Lukinmaa PL, Jernvall J, Thesleff I (2004) Tooth patterning and enamel formation can be manipulated by misexpression of TNF receptor Edar. Dev Dyn 231(2):432–440

    Article  CAS  PubMed  Google Scholar 

  • Rickels MR, Zhang X, Mumm S, Whyte MP (2005) Oropharyngeal skeletal disease accompanying high bone mass and novel LRP5 mutation. J Bone Miner Res 20(5):878–885

    Article  CAS  PubMed  Google Scholar 

  • Roessler E, Du Y, Glinka A, Dutra A, Niehrs C, Muenke M (2000) The genomic structure, chromosome location, and analysis of the human DKK1 head inducer gene as a candidate for holoprosencephaly. Cytogenet Cell Genet 89(3–4):220–224

    Article  CAS  PubMed  Google Scholar 

  • Sarkar L, Sharpe PT (1999) Expression of Wnt signalling pathway genes during tooth development. Mech Dev 85(1–2):197–200

    Article  CAS  PubMed  Google Scholar 

  • Sekine S, Shibata T, Kokubu A, Morishita Y, Noguchi M, Nakanishi Y, Sakamoto M, Hirohashi S (2002) Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations. Am J Pathol 161(6):1997–2001

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sekine S, Sato S, Takata T, Fukuda Y, Ishida T, Kishino M, Shibata T, Kanai Y, Hirohashi S (2003) Beta-catenin mutations are frequent in calcifying odontogenic cysts, but rare in ameloblastomas. Am J Pathol 163(5):1707–1712

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Siriwardena BS, Kudo Y, Ogawa I, Tilakaratne WM, Takata T (2009) Aberrant beta-catenin expression and adenomatous polyposis coli gene mutation in ameloblastoma and odontogenic carcinoma. Oral Oncol 45(2):103–108

    Article  CAS  PubMed  Google Scholar 

  • Tang R, Wang Q, Du J, Yang P, Wang X (2013) Expression and localization of Nell-1 during murine molar development. J Mol Histol 44(2):175–181

    Article  CAS  PubMed  Google Scholar 

  • van Genderen C, Okamura RM, Farinas I, Quo RG, Parslow TG, Bruhn L, Grosschedl R (1994) Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. Genes Dev 8(22):2691–2703

    Article  PubMed  Google Scholar 

  • Wang C, Zhao Y, Su Y, Li R, Lin Y, Zhou X, Ye L (2013) C-Jun N-terminal kinase (JNK) mediates Wnt5a-induced cell motility dependent or independent of RhoA pathway in human dental papilla cells. PLoS One 8(7):e69440

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yang J, Wan C, Nie S, Jian S, Sun Z, Zhang L, Chen Z (2013) Localization of Beclin1 in mouse developing tooth germs: possible implication of the interrelation between autophagy and apoptosis. J Mol Histol 44(6):619–627

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Shi J, Huang Y, Lai L (2012) Expression of canonical WNT/beta-CATENIN signaling components in the developing human lung. BMC Dev Biol 12:21

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank the Hospital for Women and Children of Fujian Province for providing aborted human embryonic tissues for this research. This study was supported by Grants from the Natural Science Foundation of China (NSFC) (No. 81200761), Natural Science Foundation of Fujian Province (2011J01146), Doctoral Program of Higher Education of China (20123503120005), Scientific Research Fund of Fujian Provincial Education Department (JA12081), and Excellent Young key Teachers Program of Fujian Normal University (fjsdjk2012077).

Author information

Authors and Affiliations

  1. Fujian Key Laboratory of Developmental and Neuro Biology, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian, 350108, People’s Republic of China

    Bingmei Wang, Hanliang Li, Ying Liu, Xin Lin, Yao Lin, Ye Wang, Xuefeng Hu & Yanding Zhang

Authors
  1. Bingmei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hanliang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xin Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yao Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ye Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xuefeng Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yanding Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bingmei Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, B., Li, H., Liu, Y. et al. Expression patterns of WNT/β-CATENIN signaling molecules during human tooth development. J Mol Hist 45, 487–496 (2014). https://doi.org/10.1007/s10735-014-9572-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-014-9572-5

Keywords

Search

Navigation