Elevated WNT signaling and compromised Hedgehog signaling due to loss of function contribute to the abnormal molar patterning.

Ellis-van Creveld (EVC) syndrome is an autosomal recessive chondrodysplasia. The affected individuals bear a series of skeleton defects, congenital heart septum anomalies, midfacial defects, and dental defects. Previous studies using or mutant mice have characterized the pathological mechanism leading to various types of congenital defects. Some patients with EVC have supernumerary tooth; however, it is not known yet if there are supernumerary tooth formed in or mutant mice, and if yes, what is the pathological mechanism associated. In the present study, we used mutant mice and analyze the pattern of molars in mutant mice at various stages. Our studies demonstrate that loss of function within the dental mesenchymal cells leads to abnormal molar patterning, and that the most anterior molar in the mutant mandible represents a supernumerary tooth. Finally, we provide evidence supporting the idea that both compromised Hedgehog signaling and elevated WNT signaling due to loss of function contributes to the supernumerary tooth formation.