Expression patterns of BMPRs in the developing mouse molar.

During development, Bone Morphogenetic Proteins (BMPs) can induce apoptosis, cell growth or differentiation. These different effects are mediated by dimers of two types of BMP-receptors (BMPRs). To identify the responding cells during tooth development and search for possible tissue-or stage-specificities in the receptors involved, the distribution patterns of BMPR-IA, -IB and -II were investigated in the mouse molar, from bud to bell stage. At the bud stage, BMP-2 was suggested to be involved in the formation of an epithelial signaling center, the primary enamel knot (PEK), while BMP-4 would mediate the condensation of the mesenchyme. Immunostaining showed the presence of BMPR-IA and -II in the epithelium instead of BMPR-IB and -II in the mesenchyme. At the cap stage, BMPR-IB was detected in the epithelium but not BMPR-II, suggesting the existence of another type II receptor to form a functional dimer. At the late cap stage in the epithelium, BMP-4, BMPR-IA and -II were restricted to the internal part of the PEK and the stalk: two apoptotic areas. The three proteins were detected in the mesenchyme, showing a strong staining where cusps were about to form. At the late bell stage, BMP-2 or -4 may induce cell differentiation. BMPR-IB and -II were detected in odontoblasts instead of BMPR-IA and -II in ameloblasts. These results provide the first evidence of multiple type I and type II BMP-receptors, expressed in the dental epithelium and mesenchyme at different stages of development, to signal different cellular activities in a time- and tissue-specific way.