AUTHOR=Zhang Honghao , Chinoy Afriti , Mousavi Paymon , Beeler Aubrey , Louie Ke’ale , Collier Crystal , Mishina Yuji TITLE=Elevated WNT signaling and compromised Hedgehog signaling due to Evc2 loss of function contribute to the abnormal molar patterning JOURNAL=Frontiers in Dental Medicine VOLUME=3 YEAR=2022 URL=https://www.frontiersin.org/journals/dental-medicine/articles/10.3389/fdmed.2022.876015 DOI=10.3389/fdmed.2022.876015 ISSN=2673-4915 ABSTRACT=

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 Evc or Evc2 mutant mice have characterized the pathological mechanism leading to various types of congenital defects. Some patients with EVC have supernumerary teeth; however, it is not known yet if supernumerary teeth have formed in Evc or Evc2 mutant mice, and if yes, what is the pathological mechanism associated. In the present study, we used Evc2 mutant mice and analyzed the pattern of molars in Evc2 mutant mice at various stages. Our studies demonstrate that Evc2 loss of function within the dental mesenchymal cells leads to abnormal molar patterning, and that the most anterior molar in the Evc2 mutant mandible represents a supernumerary tooth. Finally, we provide evidence supporting the idea that both compromised Hedgehog signaling and elevated WNT signaling due to Evc2 loss of function contribute to the supernumerary tooth formation.