Introduction

The process of development of teeth is a very complex process resulting from interactions between the ectoderm of the oral cavity, which gives rise to cells that produce enamel, and the neural crest ectomesenchyme which gives rise to the tooth structures other than enamel. At first, i.e., during the six weeks of intrauterine life, the tooth germ starts growing, and the cells forming the mineralized portion start differentiating. Thereafter, dentin and enamel matrices are laid down by these cells, which later start mineralizing. As the completed tooth erupts into the oral cavity, components of the periodontium, which includes periodontal ligament, cementum, and alveolar bone, start surrounding the root.

Development

There are four stages in the development of the tooth germ.[1][2] These stages include:

1. Bud stage
2. Cap stage
3. Early bell stage
4. Late bell stage

Bud stage: This stage starts in the eighth week of intrauterine life with the emergence of enamel organs. The enamel organs are swellings formed by dental lamina under the influence of mesenchymal cells. From these enamel, organs develop each tooth.

Cap stage: This stage is marked by the growth and expansion of the enamel organ, which results in the formation of a concavity in its inner aspect. The growth continues and at about 12 weeks of intrauterine life i.e., during the late cap stage, inner enamel epithelium forms from the inner cuboidal cells of the enamel organ. The inner enamel epithelium cells are columnar in shape, unlike enamel organ cells, which are cuboidal. This layer defines the shape of the crown and later differentiates into ameloblasts responsible for the formation of enamel. The cells from the outer layer of the enamel organ form the outer enamel epithelium and remain cuboidal. They maintain the enamel organ's shape.

The condensed mesenchymal cells beneath the inner enamel epithelium form the dental papilla, which later gives forms pulp. The enamel organ has a surrounding fibrous capsule known as the dental follicle, which later forms the periodontal ligament.

At 14 weeks of intrauterine life, apart from the inner and outer enamel epithelium, two other layers, namely stratum intermedium, and stellate reticulum, is formed. The stratum intermedium lies over the inner enamel epithelium and consists of 2 or 3 layers of cells. Its functions include transportation of the nutrients to and from the enamel forming cells, the ameloblasts. The stellate reticulum layer lies between the stratum intermedium and the outer enamel epithelium. The cells in this layer are star-shaped, hence the name stellate. Their function is to protect the underlying dental tissues and maintain the shape of the tooth.

Further growth of the inner and the outer enamel epithelium cells forms a cervical loop where the two entities meet and eventually form Hertwig's root sheath, which determines the shape of the root.

Bell stage: At this stage, the dental lamina disintegrates and is ready for the formation of dental hard tissue.

Dentine formation (Dentinogenesis): Cells from the inner enamel epithelium induce the cells at the periphery of the dental papilla to form dentin forming columnar cells i.e., odontoblasts. Initially, the odontoblasts secrete an unmineralized dentin matrix. The dentine matrix that forms before the initiation of mineralization is known as predentine. When the predentin becomes approximately 5 μm thick, mineralization begins within the matrix at random points in the form of spherical zones of hydroxyapatite called calcospherites are formed within the dentine matrix and eventually these calcospherites fuse to form mineralized dentine. The first mineralized layer of dentin is termed mantle dentine, and the remaining bulk is termed as circumpulpal dentine. As the deposition continues, the odontoblast cells retreat in the direction of dental papilla, forming an S-shaped curve. This formation leaves an elongated process known as the odontoblast process, which is later surrounded by the dentinal tubules.

Enamel formation (Amelogenesis): Enamel formation starts immediately after the first layer of dentin is laid down by the odontoblasts. The cells from the inner enamel epithelium differentiate into ameloblasts. These are columnar cells attached to the stratum intermedium via ita base. A pyramidal extension is present at the secretory end of ameloblasts known as Tomes' process through which the enamel matrix is secreted at the amelodentinal junction. Once the enamel matrix is laid down, immediately, the mineralization process begins by secretion of calcium and phosphate ions into the enamel matrix, forming hydroxyapatite crystallites. As more matrixes are secreted and mineralized, the ameloblast cells move away from the amelodentinal junction forming a pattern of crystallites contained within enamel prisms. These prisms are also known as enamel rods as they run from the amelodentinal junction to the enamel surface.

As the enamel matures, the crystallites within the enamel increase in size, and the organic content reduces. Once the enamel formation completes, the ameloblast cell loses the Tomes' process, flattens, and becomes the reduced enamel epithelium. This layer protects the enamel during eruption and eventually become the junctional epithelium.

Root formation: Once the crown formation is completed, root formation starts. The Hertwig's root sheath formed by the downward growth of the inner and outer enamel epithelium grows in the apical direction, encloses the dental papilla, and outlines the shape of the root. The dental follicle forming the periodontal ligament and cementum lies external to this sheath.

Cementum formation (Cementogenesis): After completion of the root, fragmentation of the Hertwig's root sheath occurs. This process enables the cells from the adjacent dental follicle to come into contact with the root dentine. These cells further differentiate to form cementum-forming cells termed as cementoblasts. These cells are single-layered cuboidal cells on the surface of the root dentine. The cementum matrix is secreted by these cells, and later, the process of mineralization starts by deposition of hydroxyapatite crystals. The unmineralized thin layer of cementum lying on the surface is termed as cementoid.

Periodontal ligament formation: Cells of the dental follicle other than cementoblasts differentiate into fibroblasts that secrete collagen. When the formation of cementum starts, these collagen fibers secreted by fibroblasts within the dental follicle orientate themselves into bundles perpendicular to the surface of the root and form the principal fibers of the periodontal ligament. One end of these fibers become embedded in the developing cementum, and the other end in the alveolar bone and these are known as Sharpey's fibers

Molecular Level

Studies at the molecular level have demonstrated that various paracrine signaling molecules mediate the communication between the ectoderm and ectomesenchyme during tooth development. The molecules include members of the transforming growth factor (TGF-), FGF, SHH, and wingless/int1 family of secreted signaling molecules (WNT).  When the epithelial budding starts, a signaling molecule in the tumor necrosis factor termed ectodysplasin appears in the dental placodes. Thereafter, during the transition phase from bud to cap stage, another molecule termed the enamel knot signaling center appears, one for each future cusp of the tooth. These molecules regulate morph differentiation of the tooth crown and also regulate the initiation of the secondary enamel knots responsible for the determination of the future epithelial cusp formations.[3][4] The exit of the enamel knot cells from the cell cycle is mediated by cyclin-dependent kinase inhibitors (p21). Nerve growth factor receptor (NGF-R) is necessary for morphologic and cytodifferentiation in the tooth.[5][6][7]

Additionally, the role of transcription factors including homeobox 9 gene (PAX9), MSX1, MSX2, DLX3, DLX5, DLX6, DLX7, BARX1, PITX2, LHX6, and LHX7 in tooth development have also been implicated.  These transcription factors appear to have an inductive interaction with the growth factors resulting in tooth patterning, formation, and division of the jaws into different regions corresponding to each tooth’s position.[8]

Function

Teeth play a vital role during mastication, phonetics, smiling, and giving shape to the face. The different layers of tooth i.e., enamel, dentin, pulp, and cementum, play different roles—enamel functions to protect the dentin. Dentin provides support to the overlying enamel and transmits impulses from the enamel to the dental pulp. The pulp helps in the formation of dentin and providing nutrients such as albumin, transferrin, tenascin, and other proteoglycans to the dentin. Also, it has a defensive role through the formation of new dentin, creating a barrier between irritants and slows the rate of carious decay. The cementum functions to provide attachment to the collagen fibers present in the periodontal ligament, thus maintaining the integrity of the root and its position. It is also involved in the repair and regeneration of teeth.

Pathophysiology

Any disturbance during the development of the tooth, such as disturbance in the interaction between epithelium and the mesenchyme may lead to anomaly related to number, shape, size, contour, or form. The type of anomaly depends upon the developmental stage affected. Various local and systemic factors such as local trauma, radiation damage, any nutritional deficiency, congenital disease, hormonal influences, or inflammatory process may give rise to these anomalies. The various developmental anomalies include:

Hypodontia: It is a disorder characterized by a lack of one or a few teeth and is more frequently observed in permanent teeth, particularly premolars and incisors.

Oligodontia: It refers to the development of fewer than the normal number of teeth.

Anodontia: It refers to the absence of all the teeth and may affect both primary and permanent teeth. This condition is extremely rare.

Hyperdontia: Is characterized by an increased number of teeth than the regular number of supernumerary teeth. They can occur in primary or permanent dentition. They most commonly occur in the maxillary anterior region between the incisors, in which case they are termed mesiodens. It may also occur distal to the third molar in maxilla or mandible.

Gemination: It is the condition that arises when two teeth develop from the same follicle and attempt to divide, resulting in a single tooth with two incompletely separated crowns or one incompletely separated crown but with a single root and root canal. It is sometimes also referred to as double teeth or dental twinning and is more commonly associated with the maxillary anterior region.[9][10]

Fusion: It is the condition where two teeth develop from two different dental follicles, but during the process of formation, they fuse partially or completely, resulting in a single large tooth or tooth fused completely at crown or root only. The degree of fusion depends on the stage of tooth formation at which fusion occurs. When fusion begins before the calcification stage, complete union occurs, and when it occurs at a late stage, incomplete union occurs. It is more common in the anterior region of the deciduous dentition.[11]

Concrescence: It is the fusion of two teeth at the cementum region only. It may occur either during root formation termed as true/developmental concrescence or after the completion of root formation termed as acquired/inflammatory concrescence. Unlike fusion, concrescence commonly occurs in the posterior region of the maxilla. The union of cementum may vary in degree from one small site to the involvement of the entire root surface.[12]

Dilaceration: It is a bend in the root of the tooth in any direction or deviation from the linear relationship of the crown to its root. The site of bending varies with the position of the tooth affected. In the anterior teeth, the bend presents in the apical third of the tooth, middle third in maxillary first molars, and coronal third in the third molars. Permanent teeth are commonly affected.

Dens invaginatus: It is also referred to as dens in dente or extensive compound odontoma or pregnant women anomaly and is characterized by invagination on the external surface of the tooth crown. It occurs before the calcification begins. The degree of invagination may vary from a short pit in the crown region to a deep invagination extending into the root portion or, in rare cases, even beyond the apex. A maxillary lateral incisor is the most commonly affected tooth. It can be easily identified on the radiograph by the pear-shaped invagination and narrow constriction at the opening.[13]

Dens evaginatus: It refers to an accessory cusp in the form of a tubercle or elevation or protuberance. It is also known as Leong's premolar or evaginatus odontoma or occlusal pearl. It commonly occurs on the occlusal surface of a premolar.  It may also occur in the anterior region, in which case it is referred to as Talon's cusp. The syndromes commonly associated with this anomaly include Rubinstein-Taybi syndrome, Mohr syndrome, Sturge Weber syndrome, and Berardinelli Seip syndrome.[14]

Taurodontism: It is also referred to as bull's teeth and is *characterized by teeth with abnormally large pulp chambers with furcation displaced apically, resulting in larger than normal apical-occlusal height. Molars are the most commonly affected teeth. It frequently correlates with syndromes such as Klinefelter's syndrome, Mohr syndrome, orofacial digital syndrome, and Down syndrome.

Peg laterals: It is commonly seen in the maxillary anterior region affecting the maxillary lateral incisor and is characterized by a tooth that is conical in shape with a taper in the incisal region.

Amelogenesis imperfecta: It is an inherited dental defect of the enamel characterized by abnormally soft and fragile enamel resulting in thin enamel, which can easily wear off or chip off, exposing the underlying dentin and causing yellow to brown discoloration. It affects both primary and permanent dentition.

Clinical Significance

Hypodontia poses cosmetic problems. Supernumerary teeth may lead to disturbances in eruption, crowding, and deviation of the adjacent teeth. In that case, extraction merits consideration. Gemination can also cause esthetic problems as it usually appears in the anterior region of the maxilla. Also, the attempt to divide leaves behind deep grooves on the surface of the geminated tooth, which makes it more susceptible to caries, plaque accumulation, and periodontal problems. It may sometime also interfere in the eruption process of the adjacent tooth.

Fusion may lead to crowding, occlusal disturbances, and esthetic problems. Since the fused teeth have a greater surface area and root mass, resorption may become further delayed, leading to delayed or ectopic eruption of its permanent successor.

Concrescence may give rise to complications such as a fracture of the maxillary tuberosity or floor of the maxillary sinus during the extraction of the teeth. In such cases, sectioning the tooth should precede extraction.

In dilaceration, the bend act as a nidus for bacterial invasion resulting in pulp necrosis and periapical inflammation. It poses difficulty during endodontic, orthodontic, and extraction procedures. Also, it may lead to a longer retention of the primary tooth resulting in delayed eruption or non-eruption of the permanent successor.

Dens invaginatus may act as a channel through which microorganisms enter the tooth making the tooth more susceptible to caries. Dens evaginatus, on the other hand, may fracture or abrade due to forces exerted on it when the tooth comes in occlusion; this may expose the pulp resulting in endodontic complications.

Taurodontism poses an endodontic challenge as it may be difficult to locate the canals. Peg laterals may affect the esthetic requiring prosthetic correction.