AUTHOR=Horakova Lucie , Dalecka Linda , Zahradnicek Oldrich , Lochovska Katerina , Lesot Herve , Peterkova Renata , Tucker Abigail S. , Hovorakova Maria TITLE=Eda controls the size of the enamel knot during incisor development JOURNAL=Frontiers in Physiology VOLUME=Volume 13 - 2022 YEAR=2023 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.1033130 DOI=10.3389/fphys.2022.1033130 ISSN=1664-042X ABSTRACT=Ectodysplasin (Eda) plays important roles in both shaping the developing tooth and establishing the number of teeth within the tooth row. Sonic hedgehog (Shh) has been shown to act downstream of Eda and is involved in the initiation of tooth development. Eda-/- mice possess hypoplastic and hypomineralized incisors and supernumerary teeth in the molar region. In the present study we used 3D reconstruction combined with expression analysis, cell lineage tracing experiments, and western blot analysis in order to investigate the formation of the incisor germs in Eda-/- mice. We showed that a lack of functional Eda protein during early stages of incisor tooth germ development had minimal impact on development of the early expression domains of Shh in the incisor, but had a later impact on expression in the primary enamel knot of the functional tooth. Eda-/- mice had a smaller Shh expression domain, and reduced contribution from Shh descendant cells. The reduction in the enamel knot led to the formation of an abnormal enamel organ creating a hypoplastic functional incisor. Eda therefore appears to influence the spatial formation of the successional signalling centres during odontogenesis.