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

Abstract

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 the present study the possible roles of BMP‐7 in mediating inductive events during the initiation phase of odontogenesis and mandibular morphogenesis were investigated. To do so, we have examined the effects of agarose beads soaked in recombinant BMP‐7 on E11 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 of Msx‐1, Msx‐2, and Bmp‐4 in molar‐forming mesenchyme after 24 hr. The effects 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 thickened epithelium of the early developing tooth buds, which is suggestive of cooperative and/or redundant roles of BMPs in mediating the inductive interactions during the early stages of odontogenesis. Our studies in the developing chick mandible showed that Bmp‐7 is expressed in the mandibular epithelium. In the absence of mandibular epithelium, BMP‐7 beads maintained cell proliferation and Msx expression in the medial mandibular mesenchyme and were able to induce cell proliferation, cell death, and Msx expression in the lateral chick mandibular mesenchyme. The effects of BMP‐7 on the expression of Msx genes in lateral chick mandibular mesenchyme, although different from the effects of lateral mandibular epithelium, are similar to the effects of epithelium from the medial region where multiple Bmps are expressed. We also showed that laterally placed BMP‐7 beads induced ectopic expression of Msx genes and changes in the development of posterior skeletal elements in the maxillary and mandibular arches. However, despite its proliferative effects on mandibular mesenchyme, BMP‐7 did not support the directional outgrowth of the mandible. These observations suggest that epithelial–mesenchymal interactions in the medial region of the mandibular arch regulating directional outgrowth of the mandibular mesenchyme are mediated by cooperative interactions between BMPs and other growth factors. Our observations also indicated that EGF, another growth factor implicated in mediating epithelial–mesenchymal interactions in the initiation phase of odontogenesis and morphogenesis of the developing mandible, induces an extensive translucent zone and cellular proliferation in the E11 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 data suggest that BMP‐7 is a component of the signaling network mediating epithelial–mesenchymal interactions during the initiation phase of odontogenesis and morphogenesis of the mandibular arch. Dev Dyn 1999;21...

Morphoregulation of avian beaks: Comparative mapping of growth zone activities and morphological evolution

“…The colocalization of the BMP downstream gene Msx1 and the proliferation activity in the FNM are consistent with the notion that BMP signalling is critical for beak morphogenesis. Our data are consistent with the previous studies that demonstrated that ectopic application of BMP protein-coated beads can activate MSXs gene expression in the developing facial primordia (Barlow and Francis-West, 1997;Wang et al, 1999b;Ashique et al, 2002a;Mina et al, 2002).…”

Mesenchyme-dependent BMP signaling directs the timing of mandibular osteogenesis

“…Spatiotemporal changes in Bmp4 expression correlate with the timing of osteogenic tissue interactions in the mandible, and they corroborate other BMP gene expression studies (Barlow and Francis-West, 1997;Nonaka et al, 1999). The switch of Bmp4 expression from epithelium to mesenchyme during avian osteogenesis is similar to what has been observed during mouse odontogenesis, and to what has been shown for bone development (Vainio et al, 1993;Aberg et al, 1997;Barlow and Francis-West, 1997;Tucker et al, 1998b;Nonaka et al, 1999;Wang et al, 1999). For example, this expression transition does not occur in Msx1 mutant mice, and, ultimately, results in adontia and lower jaw deficiencies (Satokata and Maas, 1994;Chen et al, 1996).…”

Msx homeobox gene family and craniofacial development

“…The Msx1-induced Bmp4 from the dental mesenchyme instructs the overlying dental epithelium to form the enamel knot, which guides tooth morphogenesis [93,110]. After the cap stage, tooth development begest that Msx1 and Msx2 mediate the inductive effects of BMP7 on mandibular morphogenesis as well as the initiation phase of odontogenesis [94]. The induction of Ptc, a downstream target of Shh signaling, in the dental mesenchyme is contingent upon Msx1, which is coexpressed with Ptc [91].…”