Analysis of Epithelial–Mesenchymal Interactions in the Initial Morphogenesis of the Mammalian Tooth

AbstractEpithelial–mesenchymal interactions govern the development of epidermal organs such as teeth. During the early stages of tooth development, a local ectodermal thickening which expresses several signaling molecules appears. It is believed that these in turn signal to the underlying mesenchyme triggering mesenchymal condensation and tooth development. For example, epithelially expressed Bmp4 inducesMsx1andLef1as well as itself in the underlying mesenchyme. In this paper we have investigated the role of four epithelial signaling molecules, Bmp2, Shh, Wnt10a, and Wnt10b, in the early inductive cascades that govern tooth development. We show that all four genes are specifically expressed in the epithelium between E11.0 and E12.0 when tooth morphogenesis is first apparent. Although Shh, Bmp2, and Wnt10b have similar, if not identical, expression patterns, each signal has a distinct molecular action on the jaw mesenchyme. Whereas Shh and Wnt10b can induce general Hedgehog and Wnt targets,PtcandGlifor Shh andLef1for Wnt10b, only Bmp2 is able to induce tooth-specific expression ofMsx1. Thus, there are distinct targets for all three pathways. Interestingly, both Bmp and Wnt signaling activateLef1, making it a candidate for integrating the two distinct signaling pathways