In this review, classical data on the early steps in human odontogenesis are summarized and updated with specific insights into the development of the upper and lower embryonic jaws to help in understanding some oral pathologies. The initial step of human odontogenesis is classically characterized by two parallel horseshoe-shaped epithelial laminae. These originate from the oral epithelium and an ingrowth into the jaw mesenchyme: the internal dental lamina gives rise to deciduous tooth primordia, while the external vestibular lamina represents the developmental base of the oral vestibule. However, a more complex situation was revealed by recent studies combining analyses of the dental and adjacent oral epithelia on histological sections and computer-aided three-dimensional (3D) reconstructions during the 2nd month of human embryonic development. The dental epithelium forms a mound, where swellings appear later, corresponding to the individual primordia of deciduous teeth. External to the developing deciduous dentition, the 3D reconstructions do not show any continuous vestibular lamina but instead a complex of discontinuous epithelial bulges and ridges. The patterns of these epithelial structures and their relationship to the dental epithelium differ not only between the upper and lower jaws but also between the lip and cheek segments in each jaw. Knowledge of early odontogenesis may help in understanding some oral pathologies. For example, the human lateral incisor has a dual origin: it arises in the area of fusion between the medial nasal and maxillary facial processes and involves material from these two regions. Such a dual origin at the site of fusion of facial processes represents a predisposition to developmental vulnerability for the upper lateral incisor, resulting in its frequent anomalies (absence, hypoplasia, duplication), especially in patients with a cleft lip and/or jaw. Other pathologies, such as a minute supernumerary tooth, desmoplastic ameloblastoma or extraosseous odontogenic cysts are located external to the upper or lower dentition, and might be derived from structures that transiently appear during early development of the oral vestibule in humans.

• Keywords
• anomaly, cleft, deciduous dentition, embryo, human, lateral incisor, oral vestibule, tooth,
• MeSH
• Jaw embryology   MeSH
• Dentition MeSH
• Humans MeSH
• Tooth embryology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

BACKGROUND: The mouse embryonic mandible comprises two types of tooth primordia in the cheek region: progressive tooth primordia of prospective functional teeth and rudimentary tooth primordia in premolar region - MS and R2. Mice lacking Sprouty genes develop supernumerary tooth in front of the lower M1 (first molar) primordium during embryogenesis. We focused on temporal-spatial dynamics of Sonic Hedgehog expression as a marker of early odontogenesis during supernumerary tooth development. RESULTS: Using mouse embryos with different dosages of Spry2 and Spry4 genes, we showed that during the normal development of M1 in the mandible the sooner appearing Shh signaling domain of the R2 bud transiently coexisted with the later appearing Shh expression domain in the early M1 primordium. Both domains subsequently fused together to form the typical signaling center representing primary enamel knot (pEK) of M1 germ at embryonic day (E) 14.5. However, in embryos with lower Spry2;Spry4 gene dosages, we observed a non-fusion of original R2 and M1 Shh signaling domains with consequent formation of a supernumerary tooth primordium from the isolated R2 bud. CONCLUSIONS: Our results bring new insight to the development of the first lower molar of mouse embryos and define simple tooth unit capable of individual development, as well as determine its influence on normal and abnormal development of the tooth row which reflect evolutionarily conserved tooth pattern. Our findings contribute significantly to existing knowledge about supernumerary tooth formation.

• MeSH
• Cell Lineage MeSH
• Embryo, Mammalian MeSH
• Gene Dosage * MeSH
• Intracellular Signaling Peptides and Proteins genetics   MeSH
• Membrane Proteins genetics   MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Protein Serine-Threonine Kinases MeSH
• Hedgehog Proteins genetics   MeSH
• Nerve Tissue Proteins genetics   MeSH
• Dental Enamel growth & development   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Intracellular Signaling Peptides and Proteins MeSH
• Membrane Proteins MeSH
• Protein Serine-Threonine Kinases MeSH
• Hedgehog Proteins MeSH
• Nerve Tissue Proteins MeSH
• Shh protein, mouse MeSH Browser
• Spry2 protein, mouse MeSH Browser
• Spry4 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

An understanding of the factors that promote or inhibit tooth development is essential for designing biological tooth replacements. The embryonic mouse dentition provides an ideal system for studying such factors because it consists of two types of tooth primordia. One type of primordium will go on to form a functional tooth, whereas the other initiates development but arrests at or before the bud stage. This developmental arrest contributes to the formation of the toothless mouse diastema. It is accompanied by the apoptosis of the rudimentary diastemal buds, which presumably results from the insufficient activity of anti-apoptotic signals such as fibroblast growth factors (FGFs). We have previously shown that the arrest of a rudimentary tooth bud can be rescued by inactivating Spry2, an antagonist of FGF signaling. Here, we studied the role of the epithelial cell death and proliferation in this process by comparing the development of a rudimentary diastemal tooth bud (R(2)) and the first molar in the mandibles of Spry2(-/-) and wild-type (WT) embryos using histological sections, image analysis and 3D reconstructions. In the WT R(2) at embryonic day 13.5, significantly increased apoptosis and decreased proliferation were found compared with the first molar. In contrast, increased levels of FGF signaling in Spry2(-/-) embryos led to significantly decreased apoptosis and increased proliferation in the R(2) bud. Consequently, the R(2) was involved in the formation of a supernumerary tooth primordium. Studies of the revitalization of rudimentary tooth primordia in mutant mice can help to lay the foundation for tooth regeneration by enhancing our knowledge of mechanisms that regulate tooth formation.

• MeSH
• Adaptor Proteins, Signal Transducing MeSH
• Apoptosis * MeSH
• In Situ Hybridization MeSH
• Intracellular Signaling Peptides and Proteins MeSH
• Membrane Proteins genetics   physiology   MeSH
• Morphogenesis MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Cell Proliferation * MeSH
• Protein Serine-Threonine Kinases MeSH
• Tooth growth & development   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Adaptor Proteins, Signal Transducing MeSH
• Intracellular Signaling Peptides and Proteins MeSH
• Membrane Proteins MeSH
• Protein Serine-Threonine Kinases MeSH
• Spry2 protein, mouse MeSH Browser