Tooth  - Development and Stem Cells

Embryonic Development of the Tooth:

Teeth are hard calcified structures located in the upper and lower jaws in the oral cavity. Mammalian teeth development is initiated in early embryogenesis and is dependent on epithelial-mesenchymal interactions. Teeth form from surface ectoderm and cranial neural crest-derived mesenchyme, in a multi-stage process, which includes initiation, morphogenesis, cytodifferentiaiton and matrix secretion, resulting in tooth eruption.

During the initiation stage, the oral epithelium thickens to form the dental placode at the site of future tooth. The underlying mesenchyme condensates and at the same time, epithelial cells continue proliferating to form the dental bud. As the dental bud continues its growth, it envelopes the underlying condensed mesenchyme, leading to formation of the mesenchymal dental papilla. Dental bud cells differentiate and give rise to the main epithelial signaling center known as enamel knot. Formation of dental papilla and enamel knots are the key events in tooth morphogenesis, which occurs at the transition from the bud to the cap stage. By the end of the cap stage, enamel knots are fully differentiated and functional. Cross-signaling between these two structures enables successful cytodifferentiation and progression through the bell stage. During the bell stage, ameloblasts, originating from the dental epithelium, and odontoblasts, originating from the mesenchymal dental papilla, are fully differentiated. Cytodifferentiation is followed by the secretion step (late bell stage), when ameloblasts and odontoblasts produce enamel and dentin, respectively, the two main matrix components of the tooth, forming a tooth crown. When the crown is formed, the tooth erupts, eliminating the ameloblasts overlying the enamel of the tooth crown. While crown formation is accomplished during embryonic development, tooth root formation occurs in mice molar teeth at postnatal stages and lasts for up to three weeks. During root formation, cementoblasts are formed from the mesenchymal tooth compartment and secrete cementum, which surrounds the forming tooth root.

Structure and Function of the Tooth:

Teeth main function is in mechanical disruption of food in preparation for swallowing. Each species has a unique set of teeth that reflects the species feeding behavior.

Humans develop deciduous (primary) and permanent sets of teeth. Primary teeth erupt at approximately six months of age and include incisor and molar teeth. The permanent set of human teeth includes incisors, canines, pre-molars and molars. The molar is comprised of a crown and a root.

The visible part of the crown is comprised of an outer enamel and inner dentin layer. Enamel is the most mineralized part of the body, where its main mineral component is crystalline calcium phosphate. The mineral composition of the enamel accounts for tooth hardness and brightness. Four main protein groups are involved in the structural organization of dental enamel: amelogenins comprise 90% of enamel proteins, enamelin is the largest protein in the enamel matrix, and ameloblastin and tuftelin, which are important for matrix formation and mineralization. The underlying dentin layer is not as hard and is essential for support of the enamel layer. Dentin is comprised of mineralized connective tissue and a collagenous matrix and forms a chamber filled with the dental pulp that includes stem cells, connective tissue, blood vessels and nerves. The root is the lower part of the tooth embedded in the jaw bone. It is mostly comprised of dentin, which includes pulp channels, and is covered by a layer of cementum, produced by cementoblasts.  The cementum is comprised of hydroxyapatite and a collagenous matrix and serves as a site of attachment for the periodontal ligaments, which provide tooth stability. Mice have only one set of teeth and its development is equivalent to that of human deciduous teeth. The molar and incisor fields are established at the early stages of embryonic development and depend on signaling from the oral epithelium.

Diseases of the Tooth:

Tooth deterioration generally occurs due to bacterial or environmental factors, where the main bacteria-related tooth conditions are dental plaque and caries. Dental plaque is formed by bacteria on the surface of the teeth, which, upon accumulation, undergoes mineralization and for dental calculus, which causes further inflammation of the gums. Caries in the tooth body leads to pain, inflammation and tooth loss, and represent one of the most common diseases throughout the world. In the United States, dental caries is the most common chronic childhood disease.

Developmental tooth abnormalities include several categories:

• Number abnormalities such as total lack of tooth development, adontia, higher than normal number of teeth, hyperdontia, lower than normal number of teeth, hypodontia.
• Size abnormalities such as abnormally small teeth, microdontia, abnormally large teeth, macrodontia.
• Structure abnormalities such as amelognesis imperfecta, when enamel does not form properly or at all, dentinogenesis imperfecta, when dentin does not form properly, dentin dysplasia, when the roots and pulp of teeth may be affected.