Tooth Induction


Tooth development is a sequential process governed by reciprocal interactions between ectoderm and neural crest‐derived mesenchyme. Initially, the inductive signal resides in the epithelium, but during subsequent developmental stages, it shifts to the mesenchyme. The complex signalling and cellular cross‐talk generate differentiated cell lineages which will ultimately form the intricate tooth structure, composed of heterogeneous cellular compartments and mineralised matrices, namely enamel, dentin and cementum. The first morphological sign of tooth development is dental lamina, a thickening of the oral epithelium at the sites of future tooth rows. Humans generate two separate dentitions: primary and permanent teeth which are formed from primary dental lamina and its extension (successional dental lamina), respectively. Many signalling pathways involved in tooth development have been identified and characterised. While some molecules demonstrate transient expression during tooth morphogenesis, many signalling pathways are active at all stages of tooth development and regulate tooth induction, morphogenesis and cytodifferentiation.

Key Concepts

  • Tooth development is regulated by a chain of epithelial–mesenchymal interactions that generate unique morphological features which mark different stages of development.
  • The first sign of tooth formation is an epithelial thickening known as the dental lamina. In humans, the initial dental lamina generates primary dentition and extends into a structure called successional lamina from which permanent teeth develop.
  • Budding morphogenesis and crown formation are regulated by signals emanating from the epithelial signalling centres called initiation knots and enamel knots, respectively.
  • Many signalling molecules and receptors are expressed at different stages of tooth development and have been shown to play important roles in the regulation of tooth morphogenesis and in induction of the differentiation of odontoblasts and ameloblasts.
  • Morphogenesis of the replacement and successionally formed teeth is similar to the morphogenesis of the primary teeth and is regulated by the same signalling pathways.

Keywords: tooth; development; induction; signal; dental lamina; initiation knot; enamel knot; stem cells; crown; root

Figure 1. Schematic presentation of the morphology of tooth development. (a) Dental lamina, a thickening of the epithelium in the upper and lower jaw, marks the initiation of teeth. (b) Individual tooth development is marked by the formation of dental placodes within the dental lamina. (c) The budding of the epithelium is driven by the Initiation Knot (IK in (a)) and accompanied by condensation of the neural crest‐derived mesenchymal cells. (d) The primary enamel knot (1°EK) appears in the epithelium as it undergoes folding morphogenesis and develops into the cap stage. Extension of the dental lamina (asterisk) marks the initiation of the secondary, replacement tooth lingually from the primary tooth. (e) The form of the tooth crown is established during the bell stage, and secondary enamel knots appear in the tips of future cusps. (f) Differentiation of the odontoblasts and ameloblasts and deposition of dentin and enamel start in the cusp tips. (g) After completion of crown formation, dentinogenesis continues in the forming roots and the tooth erupts into the oral cavity.
Figure 2. Schematic representation of signalling networks regulating the initial stages of tooth morphogenesis. The signalling tissues and genes specifically expressed in those tissues are marked in black letters, while red letters indicate signalling molecules that regulate the expression of specific transcription factors. Red arrows indicate active signalling, while grey arrows indicate continuing tooth morphogenesis.
Figure 3. Visualisation of enamel knots, signalling centres in the epithelium. (a) Transverse section of a cap stage mouse tooth (embryonic day 14). Cells of the enamel knot stop proliferating as shown by the lack of bromodeoxyuridine (BrdU) incorporation (red). (b) Three‐dimensional view of the enamel knot of the cap stage tooth as visualised by the lack of BrdU incorporation (red) and the expression of Fgf4 (blue). (c) Transverse section of a cap stage mouse tooth (embryonic day 14). Fgf‐4 expression, as visualised by in situ hybridisation (blue), is limited to the enamel knot. (d) Sagittal section of an embryonic day 16 mouse mandible. Fgf4 expression in the secondary enamel knots (sk) of the first molar (m1) at the bell stage and in the primary enamel knot (pk) of the second molar (m2) at the cap stage. de, dental epithelium; dm, dental mesenchyme. Bars, 100 µm. Courtesy of Jukka Jernvall and Päivi Kettunen.
Figure 4. Schematic of root formation. (a) Completion of crown formation and initiation of root formation coincides with disappearance of stem cells (SC) located between the inner (IEE) and outer (OEE) enamel epitheliums of the cervical loop. (b) In the developing root, cervical loops are replaced by a bilayer of IEE and OEE that fragments and forms Hertwig's epithelial root sheet (HERS). Cementum is deposited by cementoblasts differentiating from the dental follicle after the epithelial root sheath disrupts. The periodontal ligament forms and the development of alveolar bone continues.


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Further Reading

Balic A and Thesleff I (2015) Tissue Interactions Regulating Tooth Development and Renewal. Current Topics in Developmental Biology 115: 157–158.

Bei M (2009b) Molecular genetics of tooth development. Current Opinion in Genetics & Development 19 (5): 504–510.

Huang XF and Chai Y (2012) Molecular regulatory mechanism of tooth root development. International Journal of Oral Science 4 (4): 177–181.

Jernvall J and Thesleff I (2012) Tooth shape formation and tooth renewal: evolving with the same signals. Development 139 (3487–97): 2012.

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Li C‐Y, Prochazka J, Goodwin AF and Klein OD (2014) Fibroblast growth factor signaling in mammalian tooth development. Odontology 102: 1–13.

Mikkola ML (2009) Molecular aspects of hypohidrotic ectodermal dysplasia. American Journal of Medical Genetics. Part A 149A (9): 2031–2036.

Nanci A (2013) Ten Cate's Oral Histology: Development, Structure and Function. St Louis, MO: Mosby.

Ruch JV, Lesot H and Begue‐Kirn C (1995) Odontoblast differentiation. International Journal of Developmental Biology 39: 51–68.

Whitlock JA and Richman JM (2013) Biology of tooth replacement in amniotes. International Journal of Oral Science 5 (2): 66–70.

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Balic, Anamaria(Jul 2017) Tooth Induction. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001143.pub3]