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 area of the oral vestibule is often a place where pathologies appear (e.g., peripheral odontomas). The origin of these pathologies is not fully understood. In the present study, we traced a cell population expressing Sonic hedgehog (Shh) from the beginning of tooth development using Cre-LoxP system in the lower jaw of wild-type (WT) mice. We focused on Shh expression in the area of the early appearing rudimentary incisor germs located anteriorly to the prospective incisors. The localization of the labelled cells in the incisor germs and also in the inner epithelial layer of the vestibular anlage showed that the first very early developmental events in the lower incisor area are common to the vestibulum oris and the prospective incisor primordia in mice. Scanning electron microscopic analysis of human historical tooth-like structures found in the vestibular area of jaws confirmed their relation to teeth and thus the capability of the vestibular tissue to form teeth. The location of labelled cells descendant of the early appearing Shh expression domain related to the rudimentary incisor anlage not only in the rudimentary and functional incisor germs but also in the externally located anlage of the oral vestibule documented the odontogenic potential of the vestibular epithelium. This potential can be awakened under pathological conditions and become a source of pathologies in the vestibular area.

• MeSH
• Embryonic Development physiology   MeSH
• In Situ Hybridization MeSH
• Lizards embryology   metabolism   MeSH
• Humans MeSH
• Microscopy, Electron, Scanning MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Odontogenesis genetics   physiology   MeSH
• Hedgehog Proteins genetics   metabolism   MeSH
• Incisor embryology   metabolism   ultrastructure   MeSH
• Pregnancy MeSH
• Mouth embryology   metabolism   ultrastructure   MeSH
• Gene Expression Regulation, Developmental MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Hedgehog Proteins MeSH
• Shh protein, mouse MeSH Browser

Tooth development has attracted the attention of researchers since the 19th century. It became obvious even then that morphogenesis could not fully be appreciated from two-dimensional histological sections. Therefore, methods of three-dimensional (3D) reconstructions were employed to visualize the surface morphology of developing structures and to help appreciate the complexity of early tooth morphogenesis. The present review surveys the data provided by computer-aided 3D analyses to update classical knowledge of early odontogenesis in the laboratory mouse and in humans. 3D reconstructions have demonstrated that odontogenesis in the early stages is a complex process which also includes the development of rudimentary odontogenic structures with different fates. Their developmental, evolutionary, and pathological aspects are discussed. The combination of in situ hybridization and 3D reconstruction have demonstrated the temporo-spatial dynamics of the signalling centres that reflect transient existence of rudimentary tooth primordia at loci where teeth were present in ancestors. The rudiments can rescue their suppressed development and revitalize, and then their subsequent autonomous development can give rise to oral pathologies. This shows that tooth-forming potential in mammals can be greater than that observed from their functional dentitions. From this perspective, the mouse rudimentary tooth primordia represent a natural model to test possibilities of tooth regeneration.

• Keywords
• 3D reconstruction, Tooth, development, human, mouse, odontogenesis,
• MeSH
• Biological Evolution MeSH
• Dentition MeSH
• Diastema embryology   MeSH
• In Situ Hybridization methods   MeSH
• Humans MeSH
• Mice MeSH
• Odontogenesis * genetics   physiology   MeSH
• Image Processing, Computer-Assisted MeSH
• Regeneration MeSH
• Imaging, Three-Dimensional methods   MeSH
• Tooth, Supernumerary embryology   MeSH
• Tooth embryology   physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH