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Science 23 September 2005:
Vol. 309. no. 5743, pp. 2067 - 2070
DOI: 10.1126/science.1116848
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Reports

Regulation of Mammalian Tooth Cusp Patterning by Ectodin

Yoshiaki Kassai,1* Pauliina Munne,2* Yuhei Hotta,1 Enni Penttilä,2 Kathryn Kavanagh,2 Norihiko Ohbayashi,3 Shinji Takada,3 Irma Thesleff,2 Jukka Jernvall,2,4{dagger} Nobuyuki Itoh1{dagger}

Mammalian tooth crowns have precise functional requirements but cannot be substantially remodeled after eruption. In developing teeth, epithelial signaling centers, the enamel knots, form at future cusp positions and are the first signs of cusp patterns that distinguish species. We report that ectodin, a secreted bone morphogenetic protein (BMP) inhibitor, is expressed as a "negative" image of mouse enamel knots. Furthermore, we show that ectodin-deficient mice have enlarged enamel knots, highly altered cusp patterns, and extra teeth. Unlike in normal teeth, excess BMP accelerates patterning in ectodin-deficient teeth. We propose that ectodin is critical for robust spatial delineation of enamel knots and cusps.

1 Department of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501, Japan.
2 Developmental Biology Program, Institute of Biotechnology, Viikki Biocenter, Post Office Box 56, University of Helsinki, FIN-00014 Helsinki, Finland.
3 Okazaki Institute for Integrative Biosciences, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
4 Department of Ecology and Evolution, Stony Brook University, Stony Brook, NY 11794, USA.

* These authors contibuted equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: itohnobu{at}pharm.kyoto-u.ac.jp (N.I.), jernvall{at}fastmail.fm (J.J.)

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