EXPRESSION PATTERNS OF BONE MORPHOGENETIC PROTEINS (BMPS) IN THE DEVELOPING MOUSE TOOTH SUGGEST POLES IN MORPHOGENESIS AND CELL-DIFFERENTIATION

Bone morphogenetic proteins (BMP) are secretory signal molecules which have a variety of regulatory functions during morphogenesis and cell differentiation. Teeth are typical examples of vertebrate organs in wh ich development is controlled by sequential and reciprocal signaling b etween the epithelium and mesenchyme. In addition, tooth development i s characterized by formation of mineralized tissues: the bone-like den tin and cementum as well as epithelially derived enamel. We have perfo rmed a comparative in situ hybridization analysis of the expression of six different Bmps (Bmp-2 to Bmp-7) starting from initiation of tooth development to completion of crown morphogenesis when dentine and ena mel matrices are being deposited. Bmps-2, -4, and -7 were frequently c odistributed and showed marked associations with epithelial-mesenchyma l interactions. Their expression shifted between the epithelium and me senchyme starting from the stage of tooth initiation. They were subseq uently expressed in the enamel knot, the putative signaling center reg ulating tooth shape. Their expression domains prior to and during the differentiation of the dentine-forming odontoblasts and enamel-forming ameloblasts was in line with functions in regulation of cell differen tiation and/or secretory activities of the cells. The expression of Bm p-3 was confined to mesenchymal cells, in particular to the dental fol licle cells which give rise to the cementoblasts, forming the hard tis sue covering the roots of teeth. Bmp-5 was expressed only in the epith elial ameloblasts. It was upregulated as the cells started to polarize and intense expression continued in the secretory ameloblasts. Bmp-g was expressed only weakly in the dental mesenchyme during bud and cap stages. Our results are in line with regulatory functions of Bmps at a ll stages of tooth morphogenesis. Bmps-2, -4, and -7 are conceivably p arts of signaling networks regulating tooth initiation and shape devel opment. They as well as Bmp-5 may be involved in the induction and for mation of dentine and enamel, and Bmp-3 in the development of cementum . The remarkable overlaps in the expression domains of different Bmp g enes may implicate functional redundancy and/or formation of active he terodimers between different BMPs. (C) 1997 Wiley-Liss, Inc.