Identification of a Secreted BMP Antagonist, Ectodin, Integrating BMP, FGF, and SHH Signals from the Tooth Enamel Knot

The study identified a novel secreted BMP inhibitor named ectodin, which showed approximately 37% amino acid identity to sclerostin. Ectodin was secreted efficiently and inhibited BMP2, BMP4, BMP6, and BMP7 activities in mouse preosteoblastic cells, binding to these BMPs with high affinity. It was expressed in developing ectodermal organs like teeth, vibrissae, and hair follicles but was absent from hair placodes and enamel knot signaling centers. Ectodin antagonized BMP-mediated Msx2 expression in tooth explants, indicating its role as a BMP inhibitor. BMP2 and BMP7 stimulated ectodin expression, forming a feedback mechanism that was counteracted by SHH and FGF4 but not by Wnt6. The study concluded that ectodin integrates BMP signaling with SHH and FGF pathways, helping to define the BMP target field around ectodermal signaling centers.