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=13

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=<p><italic>Ectodysplasin</italic> (<italic>Eda</italic>) plays important roles in both shaping the developing tooth and establishing the number of teeth within the tooth row. <italic>Sonic hedgehog</italic> (<italic>Shh</italic>) has been shown to act downstream of <italic>Eda</italic> and is involved in the initiation of tooth development. <italic>Eda−/−</italic> mice possess hypoplastic and hypomineralized incisors and show changes in tooth number 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 <italic>Eda−/−</italic> mice. We show that a lack of functional Eda protein during early stages of incisor tooth germ development had minimal impact on development of the early expression of Shh in the incisor, a region proposed to mark formation of a rudimental incisor placode and act as an initiating signalling centre. In contrast, deficiency of Eda protein had a later impact on expression of <italic>Shh</italic> in the primary enamel knot of the functional tooth. <italic>Eda−/−</italic> mice had a smaller region where <italic>Shh</italic> was expressed, and a 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. <italic>Eda</italic> therefore appears to influence the spatial formation of the successional signalling centres during odontogenesis.</p>