Wnt/Shh interactions regulate ectodermal boundary formation during mammalian tooth development

Interactions between the Wnt (wingless) and hedgehog signaling pathways wer e first described as playing a role in establishing boundaries between ecto dermal cells in Drosophila segmentation. During the initiation of mammalian tooth development, boundaries that distinguish oral from dental ectoderm m ust be formed to correctly position the sites of tooth formation. We descri be a reciprocal relationship between the expression of Wnt-76 in presumptiv e oral ectoderm and Shh in presumptive dental ectoderm in mouse embryos tha t mark boundaries between these cells with different developmental fates. B y using a murine retrovirus to ectopically express Wnt-7b in presumptive de ntal ectoderm in mandibular arch explants. we show that Shh expression in t he ectoderm and Ptc expression in the underlying ectomesenchyme are down-re gulated, and tooth development is subsequently arrested. This suggests that Wnt-7b acts to repress Shh expression in oral ectoderm, thus maintaining t he boundaries between oral and dental ectodermal cells. Implantation of bea ds soaked in Shh protein into Wnt-7b-infected explants resulted in complete rescue of tooth development, confirming that the repressive action of Wnt- 7b specifically affects Shh signaling.