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.