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 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 Eda-/- 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 Shh in the primary enamel knot of the functional tooth. Eda-/- mice had a smaller region where Shh 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. Eda therefore appears to influence the spatial formation of the successional signalling centres during odontogenesis.

• Keywords
• mouse incisor, rudiment, shh expression, tabby mouse, tooth development,
• Publication type
• Journal Article MeSH

The vestibular lamina (VL) is a transient developmental structure that forms the lip furrow, creating a gap between the lips/cheeks and teeth (oral vestibule). Surprisingly, little is known about the development of the VL and its relationship to the adjacent dental lamina (DL), which forms the teeth. In some congenital disorders, such as Ellis-van Creveld (EVC) syndrome, development of the VL is disrupted and multiple supernumerary frenula form, physically linking the lips and teeth. Here, we assess the normal development of the VL in human embryos from 6.5 (CS19) to 13 weeks of development, showing the close relationship between the VL and DL, from initiation to differentiation. In the anterior lower region, the two structures arise from the same epithelial thickening. The VL then undergoes complex morphogenetic changes during development, forming a branched structure that separates to create the vestibule. Changing expression of keratins highlight the differentiation patterns in the VL, with fissure formation linked to the onset of filaggrin. Apoptosis is involved in removal of the central portion of the VL to create a broad furrow between the future cheek and gum. This research forms an essential base to further explore developmental defects in this part of the oral cavity.

• Keywords
• apoptosis, dental pathologies, epithelial differentiation, human development, keratin, oral mucosa,
• Publication type
• Journal Article MeSH