EDA is a member of the tumour necrosis factor family that signals through a receptor expressed locally in the placodes of all ectodermal appendages as well as in primary and secondary enamel knots (4,19). In humans, mutations in the gene encoding EDA can cause hypohidrotic ectodermal dysplasia-1 (20). This syndrome is characterized by a variety of ectodermal abnormalities, including missing teeth and defects in tooth morphology in that crowns of the remaining teeth lack cusps and are conical in shape (20). The ‘Tabby’ mouse (i.e. EDA null mutant mouse) represents the murine equivalent of hypohidrotic ectodermal dysplasia-1 (21). These mice often lack incisors and third molars and typically express simplified tooth morphology, including missing or fused cusps (22). Conversely, mice that overexpress EDA in the epithelium develop an extra tooth in front of the molars (23). The EDA locus was implicated in our previous GWA study of tooth eruption in humans (6). Our results confirm that SNPs at this locus are also associated with subtle effects on tooth development, including alterations in the timing of tooth eruption.
