|
|
|
|||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Development, Vol 125, Issue 2 161-169, Copyright © 1998 by Company of Biologists
JOURNAL ARTICLES |
J Jernvall, T Aberg, P Kettunen, S Keranen and I Thesleff
Institute of Biotechnology, University of Helsinki, Finland. jvakudaret@aol.com
The enamel knot, a transient epithelial structure, appears at the onset of mammalian tooth shape development. Until now, the morphological, cellular and molecular events leading to the formation and disappearance of the enamel knot have not been described. Here we report that the cessation of cell proliferation in the enamel knot in mouse molar teeth is linked with the expression of the cyclin-dependent kinase inhibitor p21. We show that p21 expression is induced by bone morphogenetic protein 4 (BMP-4) in isolated dental epithelia. As Bmp-4 is expressed only in the underlying dental mesenchyme at the onset of the enamel knot formation, these results support the role of the cyclin-dependent kinase inhibitors as inducible cell differentiation factors in epithelial-mesenchymal interactions. Furthermore, we show that the expression of p21 in the enamel knot is followed by Bmp-4 expression, and subsequently by apoptosis of the differentiated enamel knot cells. Three-dimensional reconstructions of serial sections after in situ hybridization and Tunel-staining indicated an exact codistribution of Bmp-4 transcripts and apoptotic cells. Apoptosis was stimulated by BMP-4 in isolated dental epithelia, but only in one third of the explants. We conclude that Bmp-4 may be involved both in the induction of the epithelial enamel knot, as a mesenchymal inducer of epithelial cyclin-dependent kinase inhibitors, and later in the termination of the enamel knot signaling functions by participating in the regulation of programmed cell death. These results show that the life history of the enamel knot is intimately linked to the initiation of tooth shape development and support the role of the enamel knot as an embryonic signaling center.
This article has been cited by other articles:
![]() |
B. Ruhin-Poncet, S. Ghoul-Mazgar, D. Hotton, F. Capron, M. H. Jaafoura, G. Goubin, and A. Berdal Msx and Dlx Homeogene Expression in Epithelial Odontogenic Tumors J. Histochem. Cytochem., January 1, 2009; 57(1): 69 - 78. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Ybot-Gonzalez, C. Gaston-Massuet, G. Girdler, J. Klingensmith, R. Arkell, N. D. E. Greene, and A. J. Copp Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling Development, September 1, 2007; 134(17): 3203 - 3211. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Sahlberg, E. Peltonen, P.-L. Lukinmaa, and S. Alaluusua Dioxin Alters Gene Expression in Mouse Embryonic Tooth Explants Journal of Dental Research, July 1, 2007; 86(7): 600 - 605. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Jarvinen, I. Salazar-Ciudad, W. Birchmeier, M. M. Taketo, J. Jernvall, and I. Thesleff Continuous tooth generation in mouse is induced by activated epithelial Wnt/beta-catenin signaling PNAS, December 5, 2006; 103(49): 18627 - 18632. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-Y. Kim, Y.-G. Cha, S.-W. Cho, E.-J. Kim, M.-J. Lee, J.-M. Lee, J. Cai, H. Ohshima, and H.-S. Jung Inhibition of Apoptosis in Early Tooth Development Alters Tooth Shape and Size Journal of Dental Research, June 1, 2006; 85(6): 530 - 535. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Fukumoto, J. H. Miner, H. Ida, E. Fukumoto, K. Yuasa, H. Miyazaki, M. P. Hoffman, and Y. Yamada Laminin {alpha}5 Is Required for Dental Epithelium Growth and Polarity and the Development of Tooth Bud and Shape J. Biol. Chem., February 24, 2006; 281(8): 5008 - 5016. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Kist, M. Watson, X. Wang, P. Cairns, C. Miles, D. J. Reid, and H. Peters Reduction of Pax9 gene dosage in an allelic series of mouse mutants causes hypodontia and oligodontia Hum. Mol. Genet., December 1, 2005; 14(23): 3605 - 3617. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Kassai, P. Munne, Y. Hotta, E. Penttila, K. Kavanagh, N. Ohbayashi, S. Takada, I. Thesleff, J. Jernvall, and N. Itoh Regulation of Mammalian Tooth Cusp Patterning by Ectodin Science, September 23, 2005; 309(5743): 2067 - 2070. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Liu, X. Sun, A. Braut, Y. Mishina, R. R. Behringer, M. Mina, and J. F. Martin Distinct functions for Bmp signaling in lip and palate fusion in mice Development, March 15, 2005; 132(6): 1453 - 1461. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Nadiri, S. Kuchler-Bopp, Y. Haikel, and H. Lesot Immunolocalization of BMP-2/-4, FGF-4, and WNT10b in the Developing Mouse First Lower Molar J. Histochem. Cytochem., January 1, 2004; 52(1): 103 - 112. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Matalova, A.S. Tucker, and P.T. Sharpe Death in the Life of a Tooth Journal of Dental Research, January 1, 2004; 83(1): 11 - 16. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Suzuki, D. Bachiller, Y. P. Chen, M. Kamikawa, H. Ogi, R. Haraguchi, Y. Ogino, Y. Minami, Y. Mishina, K. Ahn, et al. Regulation of outgrowth and apoptosis for the terminal appendage: external genitalia: development by concerted actions of BMP signaling Development, December 22, 2003; 130(25): 6209 - 6220. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Ruiz, C. Segrelles, A. Bravo, M. Santos, P. Perez, H. Leis, J. L. Jorcano, and J. M. Paramio Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130 Development, June 1, 2003; 130(11): 2341 - 2353. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Salazar-Ciudad, J. Jernvall, and S. A. Newman Mechanisms of pattern formation in development and evolution Development, May 15, 2003; 130(10): 2027 - 2037. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Yamashiro, M. Tummers, and I. Thesleff Expression of Bone Morphogenetic Proteins and Msx Genes during Root Formation Journal of Dental Research, March 1, 2003; 82(3): 172 - 176. [Abstract] [Full Text] [PDF] |
||||
![]() |
Evolution of development of the vertebrate dermal and oral skeletons: unraveling concepts, regulatory theories, and homologies Paleobiology, December 1, 2002; 28(4): 474 - 507. |
||||
![]() |
Z. Zhang, Y. Song, X. Zhao, X. Zhang, C. Fermin, and Y. Chen Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis Development, September 1, 2002; 129(17): 4135 - 4146. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. C. Yelick and T. F. Schilling MOLECULAR DISSECTION OF CRANIOFACIAL DEVELOPMENT USING ZEBRAFISH Critical Reviews in Oral Biology & Medicine, July 1, 2002; 13(4): 308 - 322. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Salazar-Ciudad and J. Jernvall A gene network model accounting for development and evolution of mammalian teeth PNAS, June 11, 2002; 99(12): 8116 - 8120. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. S. Workman, L. J. Leamy, E. J. Routman, and J. M. Cheverud Analysis of Quantitative Trait Locus Effects on the Size and Shape of Mandibular Molars in Mice Genetics, April 1, 2002; 160(4): 1573 - 1586. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Shields, K. Rogers-Graham, and C. J. Der Loss of Transgelin in Breast and Colon Tumors and in RIE-1 Cells by Ras Deregulation of Gene Expression through Raf-independent Pathways J. Biol. Chem., March 15, 2002; 277(12): 9790 - 9799. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Gritli-Linde, M. Bei, R. Maas, X. M. Zhang, A. Linde, and A. P. McMahon Shh signaling within the dental epithelium is necessary for cell proliferation, growth and polarization Development, January 12, 2002; 129(23): 5323 - 5337. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Teixeira, S. Maheswaran, and P. K. Donahoe Mullerian Inhibiting Substance: An Instructive Developmental Hormone with Diagnostic and Possible Therapeutic Applications Endocr. Rev., October 1, 2001; 22(5): 657 - 674. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. M. Panchision, J. M. Pickel, L. Studer, S.-H. Lee, P. A. Turner, T. G. Hazel, and R. D.G. McKay Sequential actions of BMP receptors control neural precursor cell production and fate Genes & Dev., August 15, 2001; 15(16): 2094 - 2110. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Thesleff, S. Keranen, and J. Jernvall Enamel Knots as Signaling Centers Linking Tooth Morphogenesis and Odontoblast Differentiation Advances in Dental Research, August 1, 2001; 15(1): 14 - 18. [Abstract] [PDF] |
||||
![]() |
F. Trousse, P. Esteve, and P. Bovolenta BMP4 Mediates Apoptotic Cell Death in the Developing Chick Eye J. Neurosci., February 15, 2001; 21(4): 1292 - 1301. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. D. Polly Development and evolution occlude: Evolution of development in mammalian teeth PNAS, December 19, 2000; 97(26): 14019 - 14021. [Full Text] [PDF] |
||||
![]() |
J. Jernvall, S. V. E. Keranen, and I. Thesleff From the Cover: Evolutionary modification of development in mammalian teeth: Quantifying gene expression patterns and topography PNAS, December 19, 2000; 97(26): 14444 - 14448. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Tucker, D. Headon, P Schneider, B. Ferguson, P Overbeek, J Tschopp, and P. Sharpe Edar/Eda interactions regulate enamel knot formation in tooth morphogenesis Development, January 11, 2000; 127(21): 4691 - 4700. [Abstract] [PDF] |
||||
![]() |
M Bei, K Kratochwil, and R. Maas BMP4 rescues a non-cell-autonomous function of Msx1 in tooth development Development, January 11, 2000; 127(21): 4711 - 4718. [Abstract] [PDF] |
||||
![]() |
H. Dassule, P Lewis, M Bei, R Maas, and A. McMahon Sonic hedgehog regulates growth and morphogenesis of the tooth Development, January 11, 2000; 127(22): 4775 - 4785. [Abstract] [PDF] |
||||
![]() |
Y Zhang, Z Zhang, X Zhao, X Yu, Y Hu, B Geronimo, S. Fromm, and Y. Chen A new function of BMP4: dual role for BMP4 in regulation of Sonic hedgehog expression in the mouse tooth germ Development, January 4, 2000; 127(7): 1431 - 1443. [Abstract] [PDF] |
||||
![]() |
A. Hollnagel, V. Oehlmann, J. Heymer, U. Ruther, and A. Nordheim Id Genes Are Direct Targets of Bone Morphogenetic Protein Induction in Embryonic Stem Cells J. Biol. Chem., July 9, 1999; 274(28): 19838 - 19845. [Abstract] [Full Text] [PDF] |
||||
![]() |
A.S. Tucker and P.T. Sharpe Molecular Genetics of Tooth Morphogenesis and Patterning: The Right Shape in the Right Place Journal of Dental Research, April 1, 1999; 78(4): 826 - 834. [Abstract] [PDF] |
||||
![]() |
R. D'Souza, T Aberg, J Gaikwad, A Cavender, M Owen, G Karsenty, and I Thesleff Cbfa1 is required for epithelial-mesenchymal interactions regulating tooth development in mice Development, January 7, 1999; 126(13): 2911 - 2920. [Abstract] [PDF] |
||||
![]() |
M Bei and R Maas FGFs and BMP4 induce both Msx1-independent and Msx1-dependent signaling pathways in early tooth development Development, January 11, 1998; 125(21): 4325 - 4333. [Abstract] [PDF] |
||||
![]() |
E. Hay, J. Lemonnier, O. Fromigue, and P. J. Marie Bone Morphogenetic Protein-2 Promotes Osteoblast Apoptosis through a Smad-independent, Protein Kinase C-dependent Signaling Pathway J. Biol. Chem., July 27, 2001; 276(31): 29028 - 29036. [Abstract] [Full Text] [PDF] |
||||