From molecules to mastication: the development and evolution of teeth

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). 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).

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 and 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.

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 Potwarmus 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. (Reprinted with permission from Ref 132. Copyright 2009 PNAS)

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.

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 six incisors, two canines, eight premolars, and six 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).

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.