Figure 1. Diagram illustrating normal tooth formation.

In the early embryo, the oral cavity is separated from underlying connective tissues by a stratified squamous epithelium. A ridge of epithelium invades connective tissue to form the dental lamina, while individual tooth germs are seen at the ‘Cap Stage’ of tooth development as ‘Dome-shaped’ thickenings in the dental lamina surrounded by condensed mesenchyme. Degeneration of the dental lamina to epithelial remnants isolates the tooth germ from the oral epithelium in the ‘Early Bell Stage’, so named because tooth germ epithelium remodels to a bell-like form, such that the inner surface defines the shape of the tooth crown and encloses condensed mesenchyme of the dental papilla, which is the future dental pulp. The dental follicle comprises condensed mesenchyme immediately surrounding the ‘bell’ epithelium, and bone begins to form surrounding the follicle. In the ‘Late Bell Stage’ of tooth development, inductive signals from the epithelium drive differentiation of dentine forming odontoblasts in the adjacent dental papilla. Progressive layers of dentine encroach on the dental papilla space, while dentine itself acts as a further inductive signal driving inner epithelial cells of the tooth germ to differentiate to enamel forming ameloblasts. Analogous to dentine, layers of enamel are deposited by ameloblasts at the expense of tooth germ epithelium, so that the tooth crown has formed by conclusion of the ‘Late Bell Stage’. Throughout, bone formation continues around the dental follicle, and the tooth germ becomes enclosed within a bony crypt embedded within the jaw. Root development is initiated by downgrowth of epithelial cells at the ‘lip of the bell’ to form an epithelial root sheath. Root sheath epithelial cells instruct dentine formation in the underlying papilla (A), and respond to the newly formed dentine by degenerating into root sheath remnants. Dentine thus becomes exposed to cells of the dental follicle, which respond by cementoblast differentiation (B). Cementoblasts then layer cementum over the exposed dentine, while cementum itself acts as a further inductive signal to cells of the follicle to form the periodontal ligament which anchors cementum to the surrounding bony crypt via dense collagen fibres (D). In this way, the root sheath defines root shape with the furthest extent of root sheath downgrowth defining the root apex, and inductive steps following root sheath degeneration establish the necessary bony attachment of teeth via the periodontal ligament [1]–[3].