Cell and Tissue Research

, Volume 365, Issue 1, pp 77–84 | Cite as

Sox2 contributes to tooth development via Wnt signaling

  • Min-Jung Lee
  • Eun-Jung Kim
  • Keishi Otsu
  • Hidemitsu Harada
  • Han-Sung Jung
Regular Article


The transcription factor Sox2 is a stem cell marker that dictates cell lineage. It has been shown to mark the epithelial stem cells of the continuously growing mouse incisors. Sox2 also interferes with Wnt signaling by binding to β-catenin, a central mediator of the Wnt pathway. We show that these functions of Sox2 are essential for mouse molar development. Sox2 has previously been shown to play a role in the formation of new teeth from the existing dental epithelium. To assess Sox2 function related to cell migration within a tooth, we monitored cell movement by using a DiI system and observed that DiI moves from molar 1 to molar 2 during tooth development. However, upon temporal knockdown of Sox2, DiI remains in the molar 1 region. This study also provides novel insights into the role of Sox2 and the important validation of Sox2 as a potent target in Wnt signaling during tooth development. Our data reveal that the degradation of Wnt signaling caused by the knockdown of Sox2 results in a lack of cell migration during tooth development.


Sox2 Tooth DiI system Cell migration Wnt signaling 


  1. Ahn Y, Sanderson BW, Klein OD, Krumlauf R (2010) Inhibition of Wnt signaling by Wise (Sostdc1) and negative feedback from Shh controls tooth number and patterning. Development 137:3221–3231CrossRefPubMedGoogle Scholar
  2. Basu-Roy U, Ambrosetti D, Favaro R, Nicolis SK, Mansukhani A, Basilico C (2010) The transcription factor Sox2 is required for osteoblast self-renewal. Cell Death Differ 17:1345–1353CrossRefPubMedPubMedCentralGoogle Scholar
  3. Chen Y, Shi L, Zhang L, Li R, Liang J, Yu W, Sun L, Yang X, Wang Y, Zhang Y, Shang Y (2008) The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer. J Biol Chem 283:17969–17978CrossRefPubMedGoogle Scholar
  4. Hütz K, Mejías-Luque R, Farsakova K, Ogris M, Krebs S, Anton M, Vieth M, Schüller U, Schneider MR, Blum H, Wagner E, Jung A, Gerhard M (2014) The stem cell factor SOX2 regulates the tumorigenic potential in human gastric cancer cells. Carcinogenesis 35:942–950CrossRefPubMedGoogle Scholar
  5. Jussila M, Crespo Yanez X, Thesleff I (2014) Initiation of teeth from the dental lamina in the ferret. Differentiation 87:32–43CrossRefPubMedGoogle Scholar
  6. Juuri E, Saito K, Ahtiainen L, Seidel K, Tummers M, Hochedlinger K, Klein OD, Thesleff I, Michon F (2012) Sox2+ stem cells contribute to all epithelial lineages of the tooth via Sfrp5+ progenitors. Dev Cell 23:317–328CrossRefPubMedPubMedCentralGoogle Scholar
  7. Juuri E, Jussila M, Seidel K, Holmes S, Wu P, Richman J, Heikinheimo K, Chuong CM, Arnold K, Hochedlinger K, Klein O, Michon F, Thesleff I (2013a) Sox2 marks epithelial competence to generate teeth in mammals and reptiles. Development 140:1424–1432CrossRefPubMedPubMedCentralGoogle Scholar
  8. Juuri E, Isaksson S, Jussila M, Heikinheimo K, Thesleff I (2013b) Expression of the stem cell marker, SOX2, in ameloblastoma and dental epithelium. Eur J Oral Sci 121:509–516CrossRefPubMedGoogle Scholar
  9. Kamachi Y, Uchikawa M, Kondoh H (2000) Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet 16:182–187CrossRefPubMedGoogle Scholar
  10. Kormish JD, Sinner D, Zorn AM (2010) Interactions between SOX factors and Wnt/beta-catenin signaling in development and disease. Dev Dyn 239:56–68PubMedPubMedCentralGoogle Scholar
  11. Lee MJ, Kim EJ, Li L, Jung HS (2015) Roles of Wnt inhibitory factor 1 during tooth morphogenesis. Cell Tissue Res 362:61–68CrossRefPubMedGoogle Scholar
  12. Lefebvre V, Dumitriu B, Penzo-Mendez A, Han Y, Pallavi B (2007) Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors. Int J Biochem Cell Biol 39:2195–2214CrossRefPubMedPubMedCentralGoogle Scholar
  13. 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 313:210–224CrossRefPubMedGoogle Scholar
  14. Liu P, Cai J, Dong D, Chen Y, Liu X, Wang Y, Zhou Y (2015) Effects of SOX2 on proliferation, migration and adhesion of human dental pulp stem cells. PLoS One 10:e0141346CrossRefPubMedPubMedCentralGoogle Scholar
  15. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using realtime quantitative PCR and the 2-Delta Delta C(T) method. Methods 2001:402–408CrossRefGoogle Scholar
  16. Mansukhani A, Ambrosetti D, Holmes G, Cornivelli L, Basilico C (2005) Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation. J Cell Biol 168:1065–1076CrossRefPubMedPubMedCentralGoogle Scholar
  17. Miyagi S, Masui S, Niwa H, Saito T, Shimazaki T, Okano H, Nishimoto M, Muramatsu M, Iwama A, Okuda A (2008) Consequence of the loss of Sox2 in the developing brain of the mouse. FEBS Lett 582:2811–2815CrossRefPubMedGoogle Scholar
  18. Numakura C, Kitanaka S, Kato M, Ishikawa S, Hamamoto Y, Katsushima Y, Kimura T, Hayasaka K (2010) Supernumerary impacted teeth in a patient with SOX2 anophthalmia syndrome. Am J Med Genet A 152A:2355–2359CrossRefPubMedGoogle Scholar
  19. Sarkar L, Sharpe PT (2000) Inhibition of Wnt signaling by exogenous Mfrzb1 protein affects molar tooth size. J Dent Res 79:920–925CrossRefPubMedGoogle Scholar
  20. Wang XP, Fan J (2011) Molecular genetics of supernumerary tooth formation. Genesis 49:261–277CrossRefPubMedPubMedCentralGoogle Scholar
  21. Yang N, Hui L, Wang Y, Yang H, Jiang X (2014) Overexpression of SOX2 promotes migration, invasion, and epithelial-mesenchymal transition through the Wnt/β-catenin pathway in laryngeal cancer Hep-2 cells. Tumour Biol 35:7965–7973CrossRefPubMedGoogle Scholar
  22. Zhang L, Yuan G, Liu H, Lin H, Wan C, Chen Z (2012) Expression pattern of Sox2 during mouse tooth development. Gene Expr Patterns 12:273–281CrossRefPubMedGoogle Scholar
  23. Zhang Y, Wang S, Song Y, Han J, Chai Y, Chen Y (2003) Timing of odontogenic neural crest cell migration and tooth-forming capability in mice. Dev Dyn 226:713–718CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Min-Jung Lee
    • 1
  • Eun-Jung Kim
    • 1
  • Keishi Otsu
    • 2
  • Hidemitsu Harada
    • 2
  • Han-Sung Jung
    • 1
    • 3
  1. 1.Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS ProjectYonsei University College of DentistrySeoulSouth Korea
  2. 2.Division of Developmental Biology and Regenerative Medicine, Department of AnatomyIwate Medical UniversityYahabaJapan
  3. 3.Oral Biosciences, Faculty of DentistryThe University of Hong KongHong Kong SARPeople’s Republic of China

Personalised recommendations