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Review
. 2013 Mar-Apr;2(2):165-82.
doi: 10.1002/wdev.63. Epub 2012 May 3.

From molecules to mastication: the development and evolution of teeth

Andrew H Jheon  1 , Kerstin Seidel, Brian Biehs, Ophir D Klein
Affiliations
Review

From molecules to mastication: the development and evolution of teeth

Andrew H Jheon et al. Wiley Interdiscip Rev Dev Biol. 2013 Mar-Apr.

Abstract

Teeth are unique to vertebrates and have played a central role in their evolution. The molecular pathways and morphogenetic processes involved in tooth development have been the focus of intense investigation over the past few decades, and the tooth is an important model system for many areas of research. Developmental biologists have exploited the clear distinction between the epithelium and the underlying mesenchyme during tooth development to elucidate reciprocal epithelial/mesenchymal interactions during organogenesis. The preservation of teeth in the fossil record makes these organs invaluable for the work of paleontologists, anthropologists, and evolutionary biologists. In addition, with the recent identification and characterization of dental stem cells, teeth have become of interest to the field of regenerative medicine. Here, we review the major research areas and studies in the development and evolution of teeth, including morphogenesis, genetics and signaling, evolution of tooth development, and dental stem cells.

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Figures

Figure 1
Figure 1. Cartoon depiction of a first lower molar from a human adult
The crown (part of the tooth covered by enamel) and the root are shown. The tooth and its supporting structure, the periodontium, contain all four mineralized tissues in the body, bone (B), cementum (Ce), dentin (De), and enamel (En). The tooth is attached to the underlying bone via periodontal ligaments (pl) in humans. The pulp chamber (p) houses the blood vessels and nerves (not shown) as well as the putative odontoblast stem cells. The gingiva (G) is the oral mucosa that overlies alveolar bone (B).
Figure 2
Figure 2. Human and mouse dentitions
The maxillary (A, C) and mandibular (B, D) dental arches show the reduced dentitions in adult human (A, B) and mouse (C, D). Both species are derived from a common mammalian ancestor that is thought to have had 6 incisors, 2 canines, 8 premolars, and 6 molars in each dental arch. The third molar or wisdom tooth (M3) is absent in the human specimen. I, incisor; I1, central incisor; I2, lateral incisor; C, canine; PM1, first premolar; PM2, second premolar; M1, first molar, M2, second molar; M3, third molar; D, diastema. Images are courtesy of Dr. Kyle Burke Jones (UCSF).
Figure 3
Figure 3. Tooth development
The various stages of mouse molar (A) and incisor (B) development, and the adult mouse mandible (C) are depicted in sagittal views. The oral epithelium thickens at the placode stage and invaginates into the neural crest-derived mesenchyme. Mesenchymal condensation occurs at the bud stage and the enamel knot, a central signaling area, first appears at the cap stage. The extracellular matrices of dentin and enamel are secreted with the differentiation of ameloblasts and odontoblasts during the bell stage. The matrix will eventually mineralize forming the tooth crown and is followed by tooth eruption. Similar developmental events occur in incisors and molars with notable differences being the presence of a vestibular lamina (VL), as well as the labial and lingual cervical loops (laCL and liCL, respectively), during incisor development, and the presence of secondary enamel knots, the future site of cusps, during molar development.
Figure 4
Figure 4. Simplified evolutionary progression of dentitions and jaws
Point A indicates the origin of pharyngeal teeth in extinct (†) jawless fish. Oral teeth and jaws are thought to have arisen at point B. The pharyngeal teeth were lost in common ancestors to tetrapods at point C. In some extant teleosts such as cichlids, both oral and pharyngeal teeth are present and pharyngeal jaws are thought to have arisen at point D. Adapted from Fraser et al.
Figure 5
Figure 5. Dental morphology of Fgf3 mutant mice and fossil rodents
As Fgf3 dosage is decreased in mice, the mesio-lingual (ML) cusp of the upper first molar is transformed into the ML crest (Fgf3+/−) and is eventually lost (Fgf3−/−), whereas the mesio-distal (MD) crest appears (Fgf3−/−). Comparisons of mutant and wild-type mice with fossil rodents such as Democricetodon, Myocricetodon, and Potswarmus show several features: during the transition from ancestral to derived morphologies, there is a loss of the MD crest, an emergence of the DL cusp, and an emergence of the ML crest that is transformed into the ML cusp in mice. The arrow indicating the relative levels of FGF signaling applies only to the allelic series of Fgf3 mutant mice, as the expression levels of Fgf3 in muroid ancestors is unknown. The following abbreviations are used for orientation: M, mesial; D, distal; V, vestibular; L, lingual. Figure adapted from Charles et al.
Figure 6
Figure 6. The adult mouse incisor
The lower incisor is shown in sagittal view (A–D). (A) The diagram indicates the two stem cell compartments in the lingual (liCL) and labial (laCL) cervical loops. Also shown are the inner enamel epithelium (IEE), from which the transit-amplifying (T-A) cells and ameloblasts (Am) arise, the outer enamel epithelium (OEE) that house the enamel stem cells in the laCL, stellate reticulum (SR), stratum intermedium (SI), odontoblasts (Od), dentin (De), enamel (En), and blood vessels (BV). (B) Adult mice were injected with BrdU for 1.5 h. BrdU-positive cells indicate rapidly proliferating cells in the T-A region. (C–D) Images from incisors of Krt5-tTA; H2B-GFP mice. In the absence of doxycycline (no Dox; C), GFP is present in all the cells expressing Krt5, which includes the OEE, IEE, SR, SI, and Am. In the presence of doxycycline (+ Dox; D) for 8 weeks, H2B-GFP expression was turned off, leading to the retention of GFP in the slowly proliferating label-retaining cells (LRCs) of the OEE. The LRCs are putative dental epithelial stem cells.
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