Effects of BMP-7 on mouse tooth mesenchyme and chick mandibular mesenchyme

BMP-7 is a member of the BMP family of signaling molecules that are thought to play key roles in mediating inductive events during embryogenesis. In t he present study the possible roles of BMP-7 in mediating inductive events during the initiation phase of odontogenesis and mandibular morphogenesis w ere investigated. To do so, we have examined the effects of agarose beads s oaked in recombinant BMP-7 on Ell mouse molar-forming mesenchyme and stage 23 chick mandibular mesenchyme, and analyzed the patterns of expression of Bmp-7 in developing mouse and chick first branchial arches. Beads releasing BMP-7 induced a translucent zone, cellular proliferation, and expression o f Msx-1, Msx-2, and Bmp-4 in molar-forming mesenchyme after 24 hr. The effe cts of BMP-7 on molar-forming mesenchyme are similar to the effects of BMP- 4 and are consistent with their overlapping patterns of expression in the t hickened epithelium of the early developing tooth buds, which is suggestive of cooperative and/or redundant roles of BMPs in mediating the inductive i nteractions during the early stages of odontogenesis. Our studies in the de veloping chick mandible showed that Bmp-7 is expressed in the mandibular ep ithelium. In the absence of mandibular epithelium, BMP-7 beads maintained c ell proliferation and Msx expression in the medial mandibular mesenchyme an d were able to induce cell proliferation, cell death, and Msx expression in the lateral chick mandibular mesenchyme. The effects of BMP-7 on the expre ssion of Msx genes in lateral chick mandibular mesenchyme, although differe nt from the effects of lateral mandibular epithelium, are similar to the ef fects of epithelium from the medial region where multiple Bmps are expresse d. We also showed that laterally placed BMP-7 beads induced ectopic express ion of Msx genes and changes in the development of posterior skeletal eleme nts in the maxillary and mandibular arches. However, despite its proliferat ive effects on mandibular mesenchyme, BMP-7 did not support the directional outgrowth of the mandible. These observations suggest that epithelial-mese nchymal interactions in the medial region of the mandibular arch regulating directional outgrowth of the mandibular mesenchyme are mediated by coopera tive interactions between BMPs and other growth factors. Our observations a lso indicated that EGF, another growth factor implicated in mediating epith elial-mesenchymal interactions in the initiation phase of odontogenesis and morphogenesis of the developing mandible, induces an extensive translucent zone and cellular proliferation in the Ell mouse molar-forming mesenchyme and stage 23 chick mandibular mesenchyme. However, in contrast to BMPs, EGF did not induce Msx-1, Msx-2, and Bmp-4, but modulated the effects of BMPs on the expression of Msx-1 and Msx-2 in these mesenchymes. Our combined dat a suggest that BMP-7 is a component of the signaling network mediating epit helial-mesenchymal interactions during the initiation phase of odontogenesi s and morphogenesis of the mandibular arch. (C) 1999 Wiley Liss, Inc.