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Disturbed tooth germ development in the absence of MINT in the cultured mouse mandibular explants

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Abstract

The Msx2-interacting nuclear target protein (MINT) is a nuclear matrix protein that regulates the development of many tissues. However, little is known regarding the role of MINT in tooth development. In this study, we prepared polyclonal antibodies against MINT, and found that that MINT was expressed in different cells at each stage of tooth germ development by immunohistochemistry. The role of MINT in tooth development was further illustrated by the misshapen and severely hypoplastic tooth organ in the cultured mandibular explants of MINT deficient mice. From the initiation to cap stage, the differences between mutants and wild-type molars were more and more distinguished histologically. In the MINT-deficient mandibular explants, the tooth germ was reduced in the overall size and lacked enamel knot, with abnormal dental lamina and collapsed stellate reticulum. Furthermore, the BrdU incorporation experiment showed that the proliferation activity was significantly reduced in MINT-deficient dental epithelium. Our results suggest that MINT plays an important role in tooth development, in particular, epithelial morphogenesis.

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References

  1. Tucker A, Sharpe P (2004) The cutting-edge of mammalian development; how the embryo makes teeth. Nat Rev Genet 5(7):499–508

    Article  CAS  PubMed  Google Scholar 

  2. Thesleff I (2003) Epithelial-mesenchymal signalling regulating tooth morphogenesis. J Cell Sci 116(Pt9):1647–1648

    Article  CAS  PubMed  Google Scholar 

  3. Takahashi C, Yoshida H, Komine A, Nakao K, Tsuji T, Tomooka Y (2009) Newly established cell lines from mouse oral epithelium regenerate teeth when combined with dental mesenchyme. In Vitro Cell Dev Biol Anim. doi:10.1007/s11626-009-9265-7

    PubMed  Google Scholar 

  4. Salazar-Ciudad I, Jernvall J (2002) A gene network model accounting for development and evolution of mammalian teeth. Proc Natl Acad Sci USA 99(12):8116–8120

    Article  CAS  PubMed  Google Scholar 

  5. Bei M (2009) Molecular genetics of tooth development. Curr Opin Genet Dev 19(5):504–510

    Article  CAS  PubMed  Google Scholar 

  6. Thesleff I, Mikkola M (2002) The role of growth factors in tooth development. Int Rev Cytol 217:93–135

    Article  CAS  PubMed  Google Scholar 

  7. Tummers M, Thesleff I (2009) The importance of signal pathway modulation in all aspects of tooth development. J Exp Zool Mol Dev Evol 312B(4):309–319

    Article  Google Scholar 

  8. Mitsiadis TA, Regaudiat L, Gridley T (2005) Role of the Notch signalling pathway in tooth morphogenesis. Arch Oral Biol 50(2):137–140

    Article  CAS  PubMed  Google Scholar 

  9. Kuroda K, Han H, Tani S, Tanigaki K, Tun T, Furukawa T, Taniguchi Y, Kurooka H, Hamada Y, Toyokuni S, Honjo T (2003) Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway. Immunity 18(2):301–312

    Article  CAS  PubMed  Google Scholar 

  10. Oswald F, Kostezka U, Astrahantseff K, Bourteele S, Dillinger K, Zechner U, Ludwig L, Wilda M, Hameister H, Knöchel W, Liptay S, Schmid RM (2002) SHARP is a novel component of the Notch/RBP-J kappa signalling pathway. EMBO J 21(20):5417–5426

    Article  CAS  PubMed  Google Scholar 

  11. Newberry EP, Latifi T, Towler DA (1999) The RRM domain of MINT, a novel Msx2 binding protein, recognizes and regulates the rat osteocalcin promoter. Biochemistry 38(33):10678–10690

    Article  CAS  PubMed  Google Scholar 

  12. Kuang B, Wu SC, Shin Y, Luo L, Kolodziej P (2000) Split ends encodes large nuclear proteins that regulate neuronal cell fate and axon extension in the Drosophila embryo. Development 127(7):1517–1529

    CAS  PubMed  Google Scholar 

  13. Chung N, Jee BK, Chae SW, Jeon YW, Lee KH, Rha HK (2009) HOX gene analysis of endothelial cell differentiation in human bone marrow-derived mesenchymal stem cells. Mol Biol Rep 36(2):227–235

    Article  CAS  PubMed  Google Scholar 

  14. Ariyoshi M, Schwabe JW (2003) A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling. Genes Dev 17(15):1909–1920

    Article  CAS  PubMed  Google Scholar 

  15. Li J, Li J, Yang X, Qin H, Zhou P, Liang Y, Han H (2005) The C terminus of MINT forms homodimers and abrogates MINT-mediated transcriptional repression. Biochim Biophys Acta 1729(1):50–56

    CAS  PubMed  Google Scholar 

  16. Tsuji M, Shinkura R, Kuroda K, Yabe D, Honjo T (2007) Msx2-interacting nuclear target protein (Mint) deficiency reveals negative regulation of early thymocyte differentiation by Notch/RBP-J signaling. Proc Natl Acad Sci USA 104(5):1610–1615

    Article  CAS  PubMed  Google Scholar 

  17. Sierra OL, Cheng SL, Loewy AP, Charlton-Kachigian N, Towler DA (2004) MINT, The Msx2 interacting nuclear matrix target, enhances Runx2-dependent activation of the Osteocalcin fibroblast growth factor response element. J Biol Chem 279(31):32913–32923

    Article  CAS  PubMed  Google Scholar 

  18. Bidder M, Latifi T, Towler DA (1998) Reciprocal temporospatial patterns of Msx2 and Osteocalcin gene expression during murine odontogenesis. J Bone Miner Res 13(4):609–619

    Article  CAS  PubMed  Google Scholar 

  19. Xiao G, Jiang D, Ge C, Zhao Z, Lai Y, Boules H, Phimphilai M, Yang X, Karsenty G, Franceschi RT (2005) Cooperative interactions between activating transcription factor 4 and Runx2/Cbfa1 stimulate osteoblast-specific osteocalcin gene expression. J Biol Chem 280(35):30689–30696

    Article  CAS  PubMed  Google Scholar 

  20. Stein GS, Lian JB, van Wijnen AJ, Stein JL (1997) The osteocalcin gene: a model for multiple parameters of skeletal-specific transcriptional control. Mol Biol Rep 24(3):185–196

    Article  CAS  PubMed  Google Scholar 

  21. Ruch JV, Lesot H, Bègue-Kirn C (1995) Odontoblast differentiation. Int J Dev Biol 39(1):51–68

    CAS  PubMed  Google Scholar 

  22. Harris SE, Harris MA (2001) Gene expression profiling in osteoblast biology: bioinformatic tools. Mol Biol Rep 28(3):139–156

    Article  CAS  PubMed  Google Scholar 

  23. Ryu YM, Hah YS, Park BW, Kim DR, Roh GS, Kim JR, Kim UK, Rho GJ, Maeng GH, Byun JH (2010) Osteogenic differentiation of human periosteal-derived cells in a three-dimensional collagen scaffold. Mol Biol Rep. doi:10.1007/s11033-010-9950-3

    Google Scholar 

  24. Yamada M, Bringas P Jr, Grodin M, MacDougall M, Cummings E, Grimmett J, Weliky B, Slavkin HC (1980) Chemically-defined organ culture of embryonic mouse tooth organs: morphogenesis, dentinogenesis and amelogenesis. J Biol Buccale 8(2):127–139

    CAS  PubMed  Google Scholar 

  25. Chai Y, Bringas P Jr, Shuler C, Devaney E, Grosschedl R, Slavkin HC (1998) A mouse mandibular culture model permits the study of neural crest cell migration and tooth development. Int J Dev Biol 42(1):87–94

    CAS  PubMed  Google Scholar 

  26. Thesleff I, Nieminen P (1996) Tooth morphogenesis and cell differentiation. Curr Opin Cell Biol 8(6):844–850

    Article  CAS  PubMed  Google Scholar 

  27. Thesleff I, Vaahtokari A, Partanen AM (1995) Regulation of organogenesis. Common molecular mechanisms regulating the development of teeth and other organs. Int J Dev Biol 39(1):35–50

    CAS  PubMed  Google Scholar 

  28. Thomas HF, Kollar EJ (1989) Differentiation of odontoblasts in grafted recombinants of murine epithelial root sheath and dental mesenchyme. Arch Oral Biol 34(1):27–35

    Article  CAS  PubMed  Google Scholar 

  29. Dassule HR, McMahon AP (1998) Analysis of epithelial-mesenchymal interactions in the initial morphogenesis of the mammalian tooth. Dev Biol 202(2):215–227

    Article  CAS  PubMed  Google Scholar 

  30. Tompkins K (2006) Molecular mechanisms of cytodifferentiation in mammalian tooth development. Connect Tissue Res 47(3):111–118

    Article  CAS  PubMed  Google Scholar 

  31. Mitsiadis TA, Lardelli M, Lendahl U, Thesleff I (1995) Expression of Notch 1, 2 and 3 is regulated by epithelial-mesenchymal interactions and retinoic acid in the developing mouse tooth and associated with determination of ameloblast cell fate. J Cell Biol 130(2):407–418

    Article  CAS  PubMed  Google Scholar 

  32. Diekwisch TG, Luan X, McIntosh JE (2002) CP27 localization in the dental lamina basement membrane and in the stellate reticulum of developing teeth. J Histochem Cytochem 50(4):583–586

    CAS  PubMed  Google Scholar 

  33. Kallenbach E (1980) Access of horseradish peroxidase (HRP) to the extracellular spaces of the maturation zone of the rat incisor enamel organ. Tissue Cell 12(1):165–174

    Article  CAS  PubMed  Google Scholar 

  34. Harada H, Kettunen P, Jung HS, Mustonen T, Wang YA, Thesleff I (1999) Localization of putative stem cells in dental epithelium and their association with notch and FGF signaling. J Cell Biol 147(1):105–120

    Article  CAS  PubMed  Google Scholar 

  35. Mustonen T, Tümmers M, Mikami T, Itoh N, Zhang N, Gridley T, Thesleff I (2002) Lunatic fringe, FGF, and BMP regulate the notch pathway during epithelial morphogenesis of teeth. Dev Biol 248(2):281–293

    Article  CAS  PubMed  Google Scholar 

  36. Sasaki T, Goldberg M, Takuma S, Garant PR (1990) Cell biology of tooth enamel formation: functional electron microscopic monographs. Monogr Oral Sci 14:1–199

    CAS  PubMed  Google Scholar 

  37. Vaahtokari A, Aberg T, Jernvall J, Keränen S, Thesleff I (1996) The enamel knot as a signaling center in the developing mouse tooth. Mech Dev 54(1):39–43

    Article  CAS  PubMed  Google Scholar 

  38. Borkosky SS, Nagatsuka H, Orita Y, Tsujigiwa H, Yoshinobu J, Gunduz M, Rodriguez AP, Missana LR, Nishizaki K, Nagai N (2008) Sequential expressions of Notch1, Jagged2 and Math1 in molar tooth germ of mouse. Biocell 32(3):251–258

    PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (30370598, 30400079, 30600342).

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Correspondence to Hua Han.

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Ming-Hui Zhu, Wen-Bo Dong, Guang-Ying Dong and Ping Zhang contributed equally to this work.

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Zhu, MH., Dong, WB., Dong, GY. et al. Disturbed tooth germ development in the absence of MINT in the cultured mouse mandibular explants. Mol Biol Rep 38, 777–784 (2011). https://doi.org/10.1007/s11033-010-0166-3

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  • DOI: https://doi.org/10.1007/s11033-010-0166-3

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