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Sox2 contributes to tooth development via Wnt signaling

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Abstract

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.

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References

  • 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 137:3221–3231

    Article  CAS  PubMed  Google Scholar 

  • 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 17:1345–1353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 283:17969–17978

    Article  CAS  PubMed  Google Scholar 

  • 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 35:942–950

    Article  PubMed  Google Scholar 

  • Jussila M, Crespo Yanez X, Thesleff I (2014) Initiation of teeth from the dental lamina in the ferret. Differentiation 87:32–43

    Article  CAS  PubMed  Google Scholar 

  • 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 23:317–328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 140:1424–1432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 121:509–516

    Article  CAS  PubMed  Google Scholar 

  • Kamachi Y, Uchikawa M, Kondoh H (2000) Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet 16:182–187

    Article  CAS  PubMed  Google Scholar 

  • Kormish JD, Sinner D, Zorn AM (2010) Interactions between SOX factors and Wnt/beta-catenin signaling in development and disease. Dev Dyn 239:56–68

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee MJ, Kim EJ, Li L, Jung HS (2015) Roles of Wnt inhibitory factor 1 during tooth morphogenesis. Cell Tissue Res 362:61–68

    Article  PubMed  Google Scholar 

  • 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 39:2195–2214

    Article  CAS  PubMed  PubMed Central  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 313:210–224

    Article  CAS  PubMed  Google Scholar 

  • 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:e0141346

    Article  PubMed  PubMed Central  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using realtime quantitative PCR and the 2-Delta Delta C(T) method. Methods 2001:402–408

    Article  Google Scholar 

  • 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 168:1065–1076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 develo** brain of the mouse. FEBS Lett 582:2811–2815

    Article  CAS  PubMed  Google Scholar 

  • 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:2355–2359

    Article  CAS  PubMed  Google Scholar 

  • Sarkar L, Sharpe PT (2000) Inhibition of Wnt signaling by exogenous Mfrzb1 protein affects molar tooth size. J Dent Res 79:920–925

    Article  CAS  PubMed  Google Scholar 

  • Wang XP, Fan J (2011) Molecular genetics of supernumerary tooth formation. Genesis 49:261–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 35:7965–7973

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Yuan G, Liu H, Lin H, Wan C, Chen Z (2012) Expression pattern of Sox2 during mouse tooth development. Gene Expr Patterns 12:273–281

    Article  CAS  PubMed  Google Scholar 

  • 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 226:713–718

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemoon-Gu, Seoul, 03722, South Korea

    Min-Jung Lee, Eun-Jung Kim & Han-Sung Jung

  2. Division of Developmental Biology and Regenerative Medicine, Department of Anatomy, Iwate Medical University, Yahaba, Japan

    Keishi Otsu & Hidemitsu Harada

  3. Oral Biosciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, People’s Republic of China

    Han-Sung Jung

Authors
  1. Min-Jung Lee
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  2. Eun-Jung Kim
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  3. Keishi Otsu
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  4. Hidemitsu Harada
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  5. Han-Sung Jung
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Corresponding author

Correspondence to Han-Sung Jung.

Additional information

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C3266). This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C1817). This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2014R1A2A1A11050764). This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIP) (No. 2012M3A9B4028738).

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Lee, MJ., Kim, EJ., Otsu, K. et al. Sox2 contributes to tooth development via Wnt signaling. Cell Tissue Res 365, 77–84 (2016). https://doi.org/10.1007/s00441-016-2363-4

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  • DOI: https://doi.org/10.1007/s00441-016-2363-4

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