12.1. Tooth Formation

Odontogenesis is the process by which tooth form, grow, and erupt in the mouth. For human teeth to have a healthy oral environment, all parts of the tooth must develop during appropriate stages of fetal development. Primary (baby) teeth start to form between the sixth and eighth week of development, and permanent teeth begin to form in the twentieth week. If teeth do not start to develop at or near these times, they will not develop at all, resulting in hypodontia (missing teeth) or anodontia (no teeth).

Overview

Watch the animations at https://www.youtube.com/watch?v=t3hR2YGdqWk or https://www.youtube.com/watch?v=wkriancp4kM for a visual introduction to the subject.

The development of a tooth is likely initiated by a chemical signal within the tissues of the first pharyngeal arch. The tooth germ is an aggregation of cells that eventually forms the tooth. These cells are derived from the ectoderm of the first pharyngeal arch and the ectomesenchyme of the neural crest. The tooth germ is organized into three parts: the enamel organ, the dental papilla and the dental sac or follicle.

The enamel organ is composed of the outer enamel epithelium, inner enamel epithelium, stellate reticulum and stratum intermedium. These cells give rise to ameloblasts, which produce enamel and become a part of the reduced enamel epithelium (REE) after maturation of the enamel. The location where the outer enamel epithelium and inner enamel epithelium join is called the cervical loop. The growth of cervical loop cells into the deeper tissues forms Hertwig Epithelial Root Sheath, which determines the root shape of the tooth. During tooth development there are strong similarities between keratinization and amelogenesis. Keratin is also present in epithelial cells of the tooth germ and a thin film of keratin is present covering the enamel on a recently erupted tooth (Nasmyth's membrane or enamel cuticle).

The dental papilla contains cells that develop into odontoblasts, which are dentin-forming cells. Additionally, the junction between the dental papilla and inner enamel epithelium determines the crown shape of a tooth. Mesenchymal cells within the dental papilla are responsible for formation of tooth pulp.

The dental sac or follicle gives rise to three important cells: cementoblasts, osteoblasts, and fibroblasts. Cementoblasts form the cementum of a tooth. Osteoblasts give rise to the alveolar bone around the roots of teeth. Fibroblasts are involved in developing the periodontal ligament which connects teeth to the alveolar bone.

Stages

Tooth development is commonly divided into the following stages: initiation stage, bud stage, cap stage, bell stage, and maturation. The staging of tooth development is an attempt to categorize changes that take place along a continuum. It has great didatic value but it is not perfect. It can be difficult to assign a stage to a particular developing tooth when it is passing from one stage to the next.

Initiation Stage

At the beginning of tooth development, two stripes of thickened epithelium called vestibular lamina and the dental lamina can be differentiated at the sites were the teeth will form. The epithelium of the dental lamina is connected to the epithelium lining the mouth and it forms several placodes. Each placode contains the thickened dental lamina and some underlining mesenchyme. It acts as a center of chemical signaling that triggers the development of several teeth. Only one tooth buds out directly from a placode, however. The other teeth that it triggers develop from the primed dental lamina.

Bud stage

The bud stage is characterized by the appearance of a tooth bud without a clear arrangement of cells at the location where the tooth will form. This occurs when epithelial cells of the dental lamina proliferate into the underlying ectomesenchyme of the jaw. Typically, this occurs when the fetus is around 8 weeks old. The tooth bud itself is the group of cells at the periphery of the dental lamina.

Ten tooth buds develop on each arch. These correspond to the 10 primary maxillary and mandibular teeth. Each bud is separated from the ectomesenchyme by a basement membrane. Some ectomesenchymal cells congregate deep to the bud and form a cluster of cells.

Cap stage

The cap stage is marked by the differentiation of cells. Some ectomesenchymal cells stop producing matrix and form an aggregation of cells called dental papilla. The epithelial portion of the tooth bud grows around the dental papilla, taking on the appearance of a cap, and becomes the enamel organ covering the dental papilla. The closest surrounding ectomesenchymal cells differentiate forming the dental sac (dental follicle). The enamel organ will eventually produce enamel, the dental papilla will produce dentin and pulp, and the dental sac will produce all the supporting structures of a tooth, the periodontium.

Bell stage

The enamel organ extends further and becomes bell-shaped during this stage. The majority of its cells are called stellate reticulum because of their star-shaped appearance. Cells on the periphery of the enamel organ differentiate into four layers: 1) A layer of cuboidal cells form the periphery of the enamel organ and it is known as the outer enamel epithelium (OEE); 2) Most of the internal volume of the enamel organ is occupied by the stellate epithelium; 3) A layer of columnar cells is found adjacent to the enamel papilla and it is known as the inner enamel epithelium (IEE); 4) Some cells remain between the IEE and the stellate reticulum and are called stratum intermedium.

Other events occur during the bell stage. The dental lamina disintegrates, breaking the epithelial connection between the developing tooth and the epithelium of the oral cavity. The developing tooth is at this point completely surrounded by ectomesenchyme. The two epithelia will not join again until the final eruption of the tooth into the mouth.

The crown of the tooth is shaped during this stage. The chemical signaling that drives the shaping of different tooth types in different tooth buds (ex.: incisors vs. canines) is an area of active research but the mechanism has not yet been fully explained.

Maturation stage

Hard tissues, including enamel and dentin, develop during the crown or maturation stage. In prior stages, all of the IEE cells were dividing to increase the overall size of the tooth bud. At the maturation stage, however, the rate of mitosis is drastically reduced where the cusps of the teeth form. The first mineralized hard tissues form at this location.

The IEE cells change in shape from cuboidal to columnar and become preameloblasts. These cells become polarized as their nuclei move closer to the stratum intermedium and away from the dental papilla.

At the dental papilla, the layer of cells adjacent to the IEE increases in size and differentiates into odontoblasts, which are the cells that form dentin. The odontoblasts secrete an organic matrix named predentin towards the enamel organ. As they do so, they congregate at the center of the dental papilla which becomes surrounded by the secreted matrix. Thus, the layer of dentin grows inward. Cytoplasmic extensions are left behind as the odontoblasts move inward. These form the dentinal tubules, which can be observed in mature teeth.

After dentin formation begins, the cells of the IEE differentiate into ameloblasts and secrete an organic matrix against the dentin. This matrix mineralizes and becomes the initial layer of the tooth's enamel. The continued deposition of enamel pushes the ameloblasts outward. Enamel is therefore deposited in the opposite direction of dentin.

Hard tissue formation

Enamel

Enamel formation is called amelogenesis. It occurs during the maturation stage of tooth development. Amelogenesis itself is divided into three stages: initiation, secretory and maturation stages. Proteins and an organic matrix form a partially mineralized enamel in the secretory stage; the maturation stage completes enamel mineralization.

During the initiation stage, the formation of predentin induces differentiation in the IEE. Its cells elongate and their nuclei migrate away from the ectomesenchyme forming ameloblasts.

In the secretory stage, ameloblasts release a soft matrix containing enamel proteins for structure. The matrix is then mineralized by the enzyme alkaline phosphatase. This phase occurs around the 3rd or 4th month of pregnancy and it marks the first appearance of enamel in the body. Ameloblasts make enamel where the cusps of the teeth will be located.

In the maturation stage, the ameloblasts transport some of the substances used in enamel formation out of the enamel. Their function changes from enamel production, as occurs in the secretory stage, to transportation of substances. Most of the materials transported in this stage are proteins used to complete mineralization, including amelogenins, ameloblastins, enamelins, and tuftelins. By the end of this stage, the enamel has completed its mineralization.

Newly erupted teeth of both dentitions may be covered by Nasmyth's membrane. This membrane consists of the outer layers of the enamel epithelium, the oral epithelium, and the dental cuticle. The later is a layer of keratin placed by the ameloblasts on the outer surface of the newly formed enamel. Nasmyth's membrane easily picks up stain from food debris. It is shortly worn away by mastication and cleaning.

Dentin

Dentin formation, known as dentinogenesis, is the first identifiable feature in the maturation stage of tooth development and it precedes the formation of enamel. As opposed to enamel, dentin can be produced throughout the live of a tooth. Four types of dentin have been identified: mantle dentin, primary dentin, secondary dentin, and tertiary dentin.

Odontoblasts differentiate from cells of the dental papilla. They begin secreting an organic matrix against the enamel organ. The organic matrix contains collagen fibers with large diameters (0.1–0.2 μm in diameter). The secretion of matrix drives the odontoblasts toward the center of the tooth. They leave behind a cellular extension called odontoblast process. This process promotes the secretion of hydroxyapatite crystals and mineralization of the matrix, which is called mantle dentin grows to about 150 μm thickness.

Primary dentin forms through a different process. As odontoblasts mature, they enlarge and become more tightly packed. This reduces the contribution of other materials in the dental papilla to the new matrix. The amount of collagen in the matrix is reduced and the resulting dentin is denser and more mineralized than mantle dentin.

Secondary dentin is formed after root formation is finished and the tooth has erupted. It occurs at a very slow rate, however. The dentin forms faster inside the crown of a tooth. This development continues throughout life and makes the pulp chamber smaller and enclosed in a wider-walled crown in older individuals than in younger ones.

Tertiary dentin is also known as reparative dentin. It involves new, localized and accelerated secretion of dentin. The process is triggered by an external stimulus such as attrition or dental caries.

Cementum

Cementum formation is called cementogenesis and occurs late in the development of teeth. Cementoblasts are the main cells active in cementogenesis. There are two types of cementum: cellular (with cells) and acellular (without cells).

Acellular cementum forms first. The cementoblasts differentiate from follicular cells. They need to contact the cervical edges of the dentin in the enamel organ, but they can only reach there when the tooth is in the maturation stage, after the epithelial cover (Hertwig's Epithelial Root Sheath) of the enamel organ has begun to deteriorate. The cementoblasts secrete fine collagen fibrils along the root surface at right angles before migrating away from the tooth. As the cementoblasts move, more collagen is deposited to lengthen and thicken the bundles of fibers. Other proteins, such as bone sialoprotein and osteocalcin, are also secreted. This forms a cementum matrix rich in proteins and fibers. The fibers deposited along the surface eventually join the forming periodontal ligaments.

Cellular cementum develops after most of the tooth formation is complete and after the tooth starts occluding against a tooth in the opposite arch. This type of cementum forms around the fiber bundles of the periodontal ligaments. The cementoblasts forming cellular cementum become trapped in the cementum they produce. Cellular cementum is usually absent in teeth with one root. In premolars and molars, cellular cementum is found only in the apical 1/3 of the roots.

Human tooth development timeline

All dental follicles are formed before birth. Their development into erupted teeth, however, follows very different time courses depending on dental set (primary or permanent), class (incisor, canine, etc) or arch.

Formation of the periodontium

The supporting structure of a tooth is called periodontium. It consists of the cementum, periodontal ligament, gingiva, and alveolar bone. Only the cementum is part of a tooth. Alveolar bone surrounds the roots of teeth to provide support and creates what is commonly called a "socket". Periodontal ligaments connect the alveolar bone to the cementum, and the gingiva is the surrounding soft tissue visible in the mouth.

Periodontal ligament

Cells from the dental follicle give rise to the periodontal ligament (PDL). Some details of the process vary between deciduous and permanent teeth and among species of animals. Fibroblasts from the dental follicle secrete collagen and bind it to fibers on the surfaces of adjacent bone and cementum. These attachments develop as the tooth erupts into the mouth. The periodontal ligament is the part of the periodontium that attaches the tooth, at the cementum, to the alveolar bone. It contains fibroblasts, epithelial cells, undifferentiated mesenchymal cells, bone cells and cementum cells. It also contains bundles of collagen fibers arranged in various orientations and attachments.

Five types of fibers attach the cementum at one end to the alveolus at the other end:

• 
  Alveolar crest fibers run from the cervical part of the root to the alveolar bone crest;
  

• Horizontal fibers run perpendicular to the long axis of the tooth, attaching the cementum to the alveolus;
  

• Oblique fibers are the most numerous fibers in the periodontal ligament, running obliquely from the cementum into a more coronal point on the bone.
  

• Apical fibers are found radiating from cementum around the apex of the root to the bone, forming base of the socket or alveolus.
  

• Interradicular fibers are found between the roots of multirooted teeth.
  
  

A sixth type of fiber called transseptal extends over the alveolar bone crest and is embedded in the cementum of adjacent teeth. It forms an interdental ligament. These fibers help to keep all the teeth aligned. Transseptal fibers may be considered part of the gingiva because they do not attach to the alveolus.

The occlusion of teeth continually affects the structure of the periodontal ligament. This perpetual maintenance of the periodontal ligament involves the formation of groups of fibers in different orientations, such as horizontal and oblique fibers.

Alveolar bone

As root and cementum formation begin, bone tissue is eroded where space is needed and produced where empty spaces are created. Alveolar osteoblast cells form from the dental follicle. Similar to the formation of primary cementum, collagen fibers are created on the surface nearest the tooth, and they remain there until attaching to periodontal ligaments.

Like any other bone in the human body, alveolar bone is remodeled throughout life. Osteoblasts create bone matrix and osteoclasts erode it, especially if force is placed on a tooth. An area of bone under compressive force tends to locally increase the activity of osteoclasts, resulting in bone resorption. This removal of bone tends to reduce the pressure, mitigating the problem. This is common when movement of teeth is attempted through orthodontic treatment using bands, wires, or appliances. An area of bone receiving tension, on the other hand, tends to locally increase the number of osteoblasts, resulting in bone formation. The addition of bone tissue tends to reduce the tension, again mitigating the problem. Teeth therefore can slowly move along the jaw in order to minimize mechanical stresses and balance them across the dentition.

Gingiva

The connection between the gingiva and the tooth is called the dentogingival junction. Hemidesmosomes form the primary epithelial attachment by anchoring the epithelium to small protein filaments on the enamel, remnants of ameloblast activity.

For details on gingival development, please refer to the chapter dedicated to the gums.

Innervation and vascularization

Nerves and blood vessels that run parallel to each other in the body are frequently formed simultaneously in the same location. This is not the case for nerves and blood vessels of teeth, however.

Nerve fibers start to near the tooth during the cap stage of tooth development and grow toward the dental follicle. Once there, the nerves develop around the tooth bud and enter the dental papilla when dentin formation has begun. Nerves never proliferate into the enamel organ.

Blood vessels grow in the dental follicle and enter the dental papilla in the cap stage. The vascularization increases until the pulp of the tooth is formed. Throughout life, the amount of pulpal tissue in a tooth decreases, and the blood supply to the tooth decreases with age. The enamel organ is devoid of blood vessels because of its epithelial origin, and the acellular tissues of enamel and dentin do not need nutrients from blood.

Tooth eruption

Tooth eruption is when a tooth ruptures the oral epithelium and becomes visible in the mouth. Osteoclasts erode the bone to create a passage for the tooth follicle, while osteoblasts add alveolar bone to the spaces behind the tooth. Tooth loss is called exfoliation, and it is naturally initiated when a primary tooth is due to be replaced by a permanent one.

The mechanism that controls the movement of the tooth during eruption is not yet fully understood. Some ideas that have been disproven over time include that the tooth is pushed upward by: (1) growth of the root; (2) growth of the bone around the tooth; (3) vascular pressure; and (4) a cushioned hammock. The cushioned hammock concept postulated that a ligament below a tooth was responsible for eruption. Later, the proposed "ligament" was determined to be merely an artifact of histological technique. Tooth eruption is currently believed to be based on gradual changes to the attachments of the periodontal ligament.

Although tooth eruption occurs at different times for different people, a general eruption timeline exists. Typically, humans have 20 primary (baby) teeth and 32 permanent teeth. Tooth eruption has three stages. The first, known as deciduous dentition stage, occurs when only primary teeth are visible. Once the first permanent tooth erupts into the mouth, the teeth are in the mixed (or transitional) dentition. After the last primary tooth falls out, the teeth are in the permanent dentition.

The period of primary dentition starts with the eruption of the mandibular central incisors, usually at eight months of age. It lasts until the first permanent molars appear in the mouth, usually when the child is six years old. The primary teeth typically erupt in the following order: (1) central incisor, (2) lateral incisor, (3) first molar, (4) canine, and (5) second molar. In general, four teeth erupt every six months, mandibular teeth erupt before their maxillary equivalents, and teeth erupt sooner in females than males. While the child has a primary dentition, the tooth buds of permanent teeth develop below the primary teeth, close to the palate or tongue.

A mixed dentition is formed by both primary and permanent teeth. This period starts when the first permanent molar appears in the mouth, usually at six years of age, and lasts until the last primary tooth is lost, usually at eleven or twelve years. Permanent teeth in the maxilla erupt in a different order from permanent teeth on the mandible.

Since there are no premolars in the primary dentition, the primary molars are replaced by permanent premolars. If any primary teeth are lost before permanent teeth are ready to replace them, some posterior teeth may drift forward and cause space to be lost in the mouth. This may cause crowding when the permanent teeth erupt.

The permanent dentition stage begins when the last primary tooth is lost, usually at age 11 or 12, and lasts for the rest of a person's life or until all of the teeth are lost (edentulism). During this stage, third molars (also called "wisdom teeth") are frequently extracted because of decay, pain or impactions. The main reasons for tooth loss are decay and periodontal disease.

Nutrition and tooth development

As in other aspects of human growth and development, nutrition has an effect on the developing tooth. Essential nutrients for a healthy tooth include calcium, phosphorus, and vitamins A, C, and D. Calcium and phosphorus are needed to properly form the hydroxyapatite crystals, and their levels in the blood are maintained by Vitamin D. Vitamin A is necessary for skin growth (formation of keratin), and vitamin C for production of collagen.

Fluoride, although not a nutrient, is incorporated into the hydroxyapatite crystal of a developing tooth and bones. Low levels of fluoride incorporation and fluoride in saliva reduce enamel demineralization and decay. Fluoride ingestion can delay eruption of teeth for as much as a year. This delay has been suggested as the reason for the apparent reduction in decay among the youngest children. Excessive fluoride ingestion during tooth development can lead to a permanent condition known as fluorosis with varying levels of severity.

Summary

Teeth start to develop very early during embryonic life. Each tooth develops in its own bud formed by the dental lamina. Ectoderm forms and enamel organ in which ameloblasts for enamel. The ectomesenchyme originates a dental papilla that forms dentin and pulp, and dental follicle which originates the periodontium. Odontoblasts in the pulp secrete the dentin and maintain it through cellular processes that extend into dentinal tubules. The pulp is irrigated by branches of the maxillary and inferior alveolar arteries. It is innervated by sensory fibers of the maxillary and mandibular branches of the trigeminal nerve. The tooth contains pain receptors and the odontoblasts respond to mechanical and thermal disturbance of the fluid in the dentinal tubules. Roots can complete their development years after the crown. Healthy dental formation requires Ca, P and vitamins A, C and D.

Key terms

Periodontium, enamel, dentin, cementum, dental pulp, hydroxyapatite, cementoblast, periodontal ligament, odontoblast, fibroblast, ameloblast, odontogenesis, cementogenesis, dentinogenesis, enamel organ, dental papilla, dental sac, dental follicle, outer enamel epithelium, inner enamel epithelium, stratum intermedium, stellate reticulum, Nasmyth’s membrane, Hertwig epithelial root sheath, initiation stage, bud stage, cap stage, bell stage, maturation stage, alkaline phosphatase, keratin, alveolar bone, osteoclast, osteoblast, bone resorption, dental placode, dental lamina, vestibular lamina, hemisdesmosome, dentogingival junction, tooth eruption, primary teeth, permanent teeth, desciduous teeth, primary dentition, mixed dentition, transitional dentition, permanent dentition, edentulism, fluoride, demineralization, fluorosis, succedaneous tooth.

Figure credits

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Figure 3 by Thesleff, I. and Tummers, M., Tooth organogenesis and regeneration (January 31, 2009), StemBook, ed. The Stem Cell Research Community, StemBook, doi/10.3824/stembook.1.37.1, http://www.stembook.org. - [1] DirectStemBook Figure 2 Histology of important stages of tooth development.Thesleff, I. and Tummers, M., Tooth organogenesis and regeneration (January 31, 2009), StemBook, ed. The Stem Cell Research Community, StemBook, doi/10.3824/stembook.1.37.1, http://www.stembook.org., CC BY 3.0, https://

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Figure 13 by OpenStax College – Anatomy and Physiology. Chapter 23.3 Fig. 4.

Figure 14 by Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below)Bartleby.com: Gray's Anatomy, Plate 1001, Public Domain, https://commons.wikimedia.org/w/index.php?curid=566943

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