Regulation of mammalian tooth cusp patterning by ectodin.
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.
Kassai
Yoshiaki
Y
Department of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501, Japan.
Munne
Pauliina
P
Hotta
Yuhei
Y
Penttilä
Enni
E
Kavanagh
Kathryn
K
Ohbayashi
Norihiko
N
Takada
Shinji
S
Thesleff
Irma
I
Jernvall
Jukka
J
Itoh
Nobuyuki
N
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019521:Body Patterning; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D002678:Chimera; D050759:Cyclin-Dependent Kinase Inhibitor p21; D003743:Dental Enamel / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008963:Molar / Q000196:embryology / Q000378:metabolism; D009154:Mutation; D009805:Odontogenesis; D009924:Organ Culture Techniques; D019228:Tooth Crown / Q000196:embryology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D053823:Hedgehog Proteins; C465570:Shh protein, mouse; C483887:Sostdc1 protein, mouse; D015534:Trans-Activators