Edar/Eda Interactions Regulate Enamel Knot Formation in Tooth Morphogenesis

The study investigated the roles of Edar and Eda, proteins involved in tooth, hair, and sweat gland development, using tabby and downless mutant mice. Edar, encoded by the downless gene, and Eda, encoded by the tabby gene, were found to interact specifically, affecting tooth morphogenesis. The research focused on the enamel knot, a critical signaling center in tooth development. In downless mutants, the enamel knot was absent, replaced by an enamel rope with altered signaling factor expression, while tabby mutants had a smaller enamel knot. Adding a soluble form of Edar to tooth germs mimicked the tabby phenotype, indicating Eda's role in tooth development, but did not replicate the downless phenotype, suggesting additional factors or mechanisms for Edar activation. The study provided insights into the enamel knot's role in tooth cusp morphogenesis and suggested that the Lef1 pathway operates independently in these processes.