THE ENAMEL KNOT AS A SIGNALING CENTER IN THE DEVELOPING MOUSE TOOTH

Mammalian tooth forms are produced during development by folding of th e enamel epithelium but the molecular mechanisms involved in the forma tion and patterning of tooth cusps are not understood. We now report t hat several key signaling molecules found in well-known vertebrate sig naling tissues such as the node, the notochord, the apical ectodermal ridge, and the zone of polarizing activity in the limb bud are specifi cally expressed in cells of the enamel knot, which is a transient clus ter of dental epithelial cells. By comparing three-dimensional reconst ructions of serial sections following in situ hybridization we localiz ed Sonic hedgehog, Bone morphogenetic proteins-2, -4 and -7, as well a s Fibroblast growth factor-4 in nested domains within the enamel knot. We suggest that the enamel knot acts as a signaling or organizing cen ter, which provides positional information for tooth morphogenesis and regulates the growth of tooth cusps.