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.
Similar content being viewed by others
References
Tucker A, Sharpe P (2004) The cutting-edge of mammalian development; how the embryo makes teeth. Nat Rev Genet 5(7):499–508
Thesleff I (2003) Epithelial-mesenchymal signalling regulating tooth morphogenesis. J Cell Sci 116(Pt9):1647–1648
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
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
Bei M (2009) Molecular genetics of tooth development. Curr Opin Genet Dev 19(5):504–510
Thesleff I, Mikkola M (2002) The role of growth factors in tooth development. Int Rev Cytol 217:93–135
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
Mitsiadis TA, Regaudiat L, Gridley T (2005) Role of the Notch signalling pathway in tooth morphogenesis. Arch Oral Biol 50(2):137–140
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
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
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
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
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
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
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
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
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
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
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
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
Ruch JV, Lesot H, Bègue-Kirn C (1995) Odontoblast differentiation. Int J Dev Biol 39(1):51–68
Harris SE, Harris MA (2001) Gene expression profiling in osteoblast biology: bioinformatic tools. Mol Biol Rep 28(3):139–156
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
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
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
Thesleff I, Nieminen P (1996) Tooth morphogenesis and cell differentiation. Curr Opin Cell Biol 8(6):844–850
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
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
Dassule HR, McMahon AP (1998) Analysis of epithelial-mesenchymal interactions in the initial morphogenesis of the mammalian tooth. Dev Biol 202(2):215–227
Tompkins K (2006) Molecular mechanisms of cytodifferentiation in mammalian tooth development. Connect Tissue Res 47(3):111–118
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
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
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
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
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
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
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
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
Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (30370598, 30400079, 30600342).
Author information
Authors and Affiliations
Corresponding author
Additional information
Ming-Hui Zhu, Wen-Bo Dong, Guang-Ying Dong and Ping Zhang contributed equally to this work.
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-010-0166-3