right|300px|thumb|Radiograph of lower right (from left to right) third, second, and first molars in different stages of development
thumb|X-ray of teeth of a boy aged 5 years showing left lower primary molar and developing crowns of left lower permanent premolar (below primary molar) and permanent molars
Tooth development or odontogenesis is the complex process by which teeth form from embryonic cells, grow, and erupt into 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 prenatal 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 or anodontia.
A significant amount of research has focused on determining the processes that initiate tooth development. It is widely accepted that there is a factor within the tissues of the first pharyngeal arch that is necessary for the development of teeth. 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. Keratin is also present in epithelial cells of tooth germ and a thin film of keratin is present 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.
NGF-R is present in the condensing ectomesenchymal cells of the dental papilla in the early cap stage tooth germ and plays multiple roles during morphogenetic and cytodifferentiation events in the tooth. There is a relationship between tooth agenesis and absence of the peripheral trigeminal nerve (see Hypodontia).
All stages (bud, cap, bell, crown), growth and morphogenesis of the teeth are regulated by a protein called sonic hedgehog.
Various phenotypic inputs modulate the size of the teeth.
Parathyroid hormone is required for tooth eruption.
Human tooth development timeline
The following tables present the development timeline of human teeth. Times for the initial calcification of primary teeth are for weeks in utero. Abbreviations: wk = weeks; mo = months; yr = years.
<div style="font-size: 90%">
{| class="wikitable" style="margin:1em auto; border-collapse:collapse;padding:3px;text-align:center;" border="BORDER"
!
! colspan=8 style="background:#ffdead;padding:3px" | Maxillary (upper) teeth
|-
! style="width:10em" | Primary teeth
! style="width:5em;"| Central<br/>incisor
! style="width:5em;"| Lateral<br/>incisor
! style="width:5em;"| <br/>Canine
! style="width:5em;"| First<br/>molar
! style="width:5em;"| Second<br/>molar
|-
| style="padding:3px" | Initial calcification
| 14 wk I.U.
| 16 wk I.U.
| 17 wk I.U.
| 15.5 wk I.U.
| 19 wk I.U.
|-
| style="padding:3px" | Crown completed
| 1.5 mo
| 2.5 mo
| 9 mo
| 6 mo
| 11 mo
|-
| style="padding:3px" | Root completed
| 1.5 yr
| 2 yr
| 3.25 yr
| 2.5 yr
| 3 yr
|-
!
! colspan=8 style="background:#ffdead;padding:3px" | Mandibular (lower) teeth
|-
| style="padding:3px" | Initial calcification
| 14 wk I.U.
| 16 wk I.U.
| 17 wk I.U.
| 15.5 wk I.U.
| 18 wk I.U.
|-
| style="padding:3px" | Crown completed
| 2.5 mo
| 3 mo
| 9 mo
| 5.5 mo
| 10 mo
|-
| style="padding:3px" | Root completed
| 1.5 yr
| 1.5 yr
| 3.25 yr
| 2.5 yr
| 3 yr
|}
{| class="wikitable" style="margin:1em auto; border-collapse:collapse;padding:3px;text-align:center" border="BORDER"
!
! colspan=8 style="background:#ffdead;padding:3px" | Maxillary (upper) teeth
|-
! style="width:10em" | Permanent teeth
! style="width:5em;"| Central<br/>incisor
! style="width:5em;"| Lateral<br/>incisor
! style="width:5em;"| <br/>Canine
! style="width:5em;"| First<br/>premolar
! style="width:5em;"| Second<br/>premolar
! style="width:5em;"| First<br/>molar
! style="width:5em;"| Second<br/>molar
! style="width:5em;"| Third<br/>molar
|-
| style="padding:3px" | Initial calcification
| 3–4 mo
| 10–12 mo
| 4–5 mo
| 1.5–1.75 yr
| 2–2.25 yr
| at birth
| 2.5–3 yr
| 7–9 yr
|-
| style="padding:3px" | Crown completed
| 4–5 yr
| 4–5 yr
| 6–7 yr
| 5–6 yr
| 6–7 yr
| 2.5–3 yr
| 7–8 yr
| 12–16 yr
|-
| style="padding:3px" | Root completed
| 10 yr
| 11 yr
| 13–15 yr
| 12–13 yr
| 12–14 yr
| 9–10 yr
| 14–16 yr
| 18–25 yr
|-
!
! colspan=8 style="background:#ffdead;padding:3px" | Mandibular (lower) teeth
|-
| style="padding:3px" | Initial calcification
| 3–4 mo
| 3–4 mo
| 4–5 mo
| 1.5–2 yr
| 2.25–2.5 yr
| at birth
| 2.5–3 yr
| 8–10 yr
|-
| style="padding:3px" | Crown completed
| 4–5 yr
| 4–5 yr
| 6–7 yr
| 5–6 yr
| 6–7 yr
| 2.5–3 yr
| 7–8 yr
| 12–16 yr
|-
| style="padding:3px" | Root completed
| 9 yr
| 10 yr
| 12–14 yr
| 12–13 yr
| 13–14 yr
| 9–10 yr
| 14–15 yr
| 18–25 yr
|}
</div>
Stages
thumb|Histology of important stages of tooth development
alt=Animation of major stages in early tooth development|thumb|Animation of major stages in early tooth development
Tooth development is commonly divided into the following stages: the initiation stage, the bud stage, the cap stage, the bell stage, and finally maturation. The staging of tooth development is an attempt to categorize changes that take place along a continuum; frequently it is difficult to decide what stage should be assigned to a particular developing tooth. This determination is further complicated by the varying appearance of different histologic sections of the same developing tooth, which can appear to be different stages. This is regarded as the initiation stage. The tooth bud itself is the group of cells at the periphery of the dental lamina.
Along with the formation of the dental lamina, 10 round epithelial structures, each referred to as a bud, develop at the distal aspect of the dental lamina of each arch. These correspond to the 10 primary teeth of each dental arch, and they signify the bud stage of tooth development. Each bud is separated from the ectomesenchyme by a basement membrane. Ectomesenchymal cells congregate deep to the bud, forming a cluster of cells, which is the initiation of the condensation of the ectomesenchyme. The remaining ectomesenchymal cells are arranged in a more or less haphazardly uniform fashion.
Cap stage
right|150px|thumb|Histologic slide of tooth in cap stage
The first signs of an arrangement of cells in the tooth bud occur in the cap stage. A small group of ectomesenchymal cells stops producing extracellular substances, which results in an aggregation of these cells called the dental papilla. At this point, the tooth bud grows around the ectomesenchymal aggregation, taking on the appearance of a cap, and becomes the enamel (or dental) organ covering the dental papilla. A condensation of ectomesenchymal cells called the dental sac or follicle surrounds the enamel organ and limits the dental papilla. Eventually, the enamel organ will 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.
In summary, the layers in order of innermost to outermost consist of dentin, enamel (formed by IEE, or 'ameloblasts', as they move outwards/upwards), inner enamel epithelium and stratum intermedium (stratified cells that support the synthetic activity of the inner enamel epithelium) What follows is part of the initial 'enamel organ', the center of which is made up of stellate reticulum cells that serve to protect the enamel organ. This is all encased by the OEE layer.
Other events occur during the bell stage. The dental lamina disintegrates, leaving the developing teeth completely separated from the epithelium of the oral cavity; the two will not join again until the final eruption of the tooth into the mouth. Researchers believe that the odontoblasts would not form if it were not for the changes occurring in the IEE. As the changes to the IEE and the formation of odontoblasts continue from the tips of the cusps, the odontoblasts secrete a substance, an organic matrix, into their immediate surrounding. The organic matrix contains the material needed for dentin formation. As odontoblasts deposit organic matrix termed predentin, they migrate toward the center of the dental papilla. Thus, unlike enamel, dentin starts forming in the surface closest to the outside of the tooth and proceeds inward. Cytoplasmic extensions are left behind as the odontoblasts move inward. The unique, tubular microscopic appearance of dentin is a result of the formation of dentin around these extensions. Generally, enamel formation occurs in two stages: the secretory and maturation stages. Proteins and an organic matrix form a partially mineralized enamel in the secretory stage; the maturation stage completes enamel mineralization.
In the secretory stage, ameloblasts release enamel proteins that contribute to the enamel matrix, which is then partially mineralized by the enzyme alkaline phosphatase. This mineralized phase occurs very early around the 3rd or 4th month of pregnancy. This marks the first appearance of enamel in the body. Ameloblasts make enamel at the location of where the cusps of the teeth are located. Enamel grows outwards, away from the center of the tooth.
In the maturation stage, the ameloblasts transport some of the substances used in enamel formation out of the enamel. Thus, the function of ameloblasts changes from enamel production, as occurs in the secretory stage, to transportation of substances. Most of the materials transported by ameloblasts in this stage are proteins used to complete mineralization. The important proteins involved are amelogenins, ameloblastins, enamelins, and tuftelins. By the end of this stage, the enamel has completed its mineralization.
A residue may form on newly erupted teeth of both dentitions that may leave the teeth extrinsically stained. This green-gray residue, Nasmyth membrane, consists of the fused tissue of the reduced enamel epithelium and oral epithelium, as well as the dental cuticle placed by the ameloblasts on the newly formed outer enamel surface. Nasmyth membrane then easily picks up stain from food debris and is hard to remove except by selective polishing. The child's supervising adults may need reassurance that it is only an extrinsic stain on a child's newly erupted teeth.
Patients with osteopetrosis display enamel abnormalities, suggesting that the a3 gene mutation found in V-ATPases also plays a role in the development of hypomineralized and hypoplastic enamel.
Dentin
Dentin formation, known as dentinogenesis, is the first identifiable feature in the crown stage of tooth development. The formation of dentin must always occur before the formation of enamel. The different stages of dentin formation result in different types of dentin: mantle dentin, primary dentin, secondary dentin, and tertiary dentin.
Odontoblasts, the dentin-forming cells, differentiate from cells of the dental papilla. They begin secreting an organic matrix around the area directly adjacent to the inner enamel epithelium, closest to the area of the future cusp of a tooth. The organic matrix contains collagen fibers with large diameters (0.1–0.2 μm in diameter). The odontoblasts begin to move toward the center of the tooth, forming an extension called the odontoblast process. This development continues throughout life and accounts for the smaller areas of pulp found in older individuals.
left|200px|thumb|Cross-section of tooth at root. Note clear, acellular appearance of cementum.<br/>A: dentin<br/>B: cementum
Cementum
Cementum formation is called cementogenesis and occurs late in the development of teeth. Cementoblasts are the cells responsible for cementogenesis. Two types of cementum form: cellular and acellular.
Acellular cementum forms first. The cementoblasts differentiate from follicular cells, which can only reach the surface of the tooth's root once Hertwig's Epithelial Root Sheath (HERS) 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. Noncollagenous proteins, such as bone sialoprotein and osteocalcin, are also secreted. Acellular cementum contains a secreted matrix of proteins and fibers. As mineralization takes place, the cementoblasts move away from the cementum, and the fibers left along the surface eventually join the forming periodontal ligaments.
Cellular cementum develops after most of the tooth formation is complete and after the tooth occludes (in contact) with a tooth in the opposite arch.
Periodontal ligament
Cells from the dental follicle give rise to the periodontal ligament (PDL). Specific events leading to the formation of the periodontal ligament vary between deciduous (baby) and permanent teeth and among various species of animals. As is the case when movement of teeth is attempted through orthodontics using bands, wires, or appliances, an area of bone under compressive force from a tooth moving toward it has a high osteoclast level, resulting in bone resorption. An area of bone receiving tension from periodontal ligaments attached to a tooth moving away from it has a high number of osteoblasts, resulting in bone formation. Thus, the tooth or teeth are slowly moved along the jaw so as to achieve a dentition that works in harmony. In this way, the width of the space between the alveoli and the root is kept about the same.
Gingiva
The connection between the gingiva and the tooth is called the dentogingival junction. This junction has three epithelial types: gingival, sulcular, and junctional epithelium. These three types form from a mass of epithelial cells known as the epithelial cuff between the tooth and the mouth. Some commonly held theories that have been disproven over time include: (1) the tooth is pushed upward into the mouth by the growth of the tooth's root, (2) the tooth is pushed upward by the growth of the bone around the tooth, (3) the tooth is pushed upward by vascular pressure, and (4) the tooth is pushed upward by the cushioned hammock. The cushioned hammock theory, first proposed by Harry Sicher, was taught widely from the 1930s to the 1950s. This theory postulated that a ligament below a tooth, which Sicher observed under a microscope on a histologic slide, was responsible for eruption. Later, the "ligament" Sicher observed was determined to be merely an artifact created in the process of preparing the slide.
The most widely held current theory is that while several forces might be involved in eruption, the periodontal ligaments provide the main impetus for the process. Theorists hypothesize that the periodontal ligaments promote eruption through the shrinking and cross-linking of their collagen fibers and the contraction of their fibroblasts.
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 of the mouth—a process known as exfoliation—the teeth are in the permanent dentition.
Primary dentition starts on the arrival of the mandibular central incisors, usually at eight months, and lasts until the first permanent molars appear in the mouth, usually at six years. The primary teeth typically erupt in the following order: (1) central incisor, (2) lateral incisor, (3) first molar, (4) canine, and (5) second molar. As a general rule, four teeth erupt for every six months of life, mandibular teeth erupt before maxillary teeth, and teeth erupt sooner in females than males. During primary dentition, the tooth buds of permanent teeth develop below the primary teeth, close to the palate or tongue.
Mixed dentition starts when the first permanent molar appears in the mouth, usually at six years, 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. Maxillary teeth erupt in the following order: (1) first molar (2) central incisor, (3) lateral incisor, (4) first premolar, (5) second premolar, (6) canine, (7) second molar, and (8) third molar. Mandibular teeth erupt in the following order: (1) first molar (2) central incisor, (3) lateral incisor, (4) canine, (5) first premolar, (6) second premolar, (7) second molar, and (8) third molar. 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 and/or misplacement once the permanent teeth erupt, which is usually referred to as malocclusion. Orthodontics may be required in such circumstances for an individual to achieve a straight set of teeth.
The permanent dentition begins when the last primary tooth is lost, usually at 11 to 12 years, 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.
<div style="font-size: 90%;">
{| class="wikitable" style="margin:1em auto; border-collapse:collapse;padding:3px;text-align:center" border="BORDER"
|+Eruption times for primary and permanent teeth
!
! colspan=8 style="background:#ffdead;padding:3px" | Primary teeth
|-
!style="width:10em" | Teeth
! style="width:5em;"| Central<br/>incisor
! style="width:5em;"| Lateral<br/>incisor
! style="width:5em;"| <br/>Canine
! style="width:5em;"| First<br/>premolar
! style="width:5em;"| Second<br/>premolar
! style="width:5em;"| First<br/>molar
! style="width:5em;"| Second<br/>molar
! style="width:5em;"| Third<br/>molar
|-
| style="padding:3px" | Maxillary teeth
| 10 mo
| 11 mo
| 19 mo
| -
| -
| -16 mo
| -29 mo
| -
|-
| style="padding:3px" | Mandibular teeth
| 8 mo
| 13 mo
| 20 mo
| -
| -
| -16 mo
| -27 mo
| -
|-
!
! colspan=8 style="background:#ffdead;padding:3px" | Permanent teeth
|-
!Teeth
!| Central<br/>incisor
!| Lateral<br/>incisor
!| <br/>Canine
!| First<br/>premolar
!| Second<br/>premolar
!| First<br/>molar
!| Second<br/>molar
!| Third<br/>molar
|-
| style="padding:3px" | Maxillary teeth
| 7–8 yr
| 8–9 yr
| 11–12 yr
| 10–11 yr
| 10–12 yr
| 6–7 yr
| 12–13 yr
| 17–21 yr
|-
| style="padding:3px" | Mandibular teeth
| 6–7 yr
| 7–8 yr
| 9–10 yr
| 10–12 yr
| 11–12 yr
| 6–7 yr
| 11–13 yr
| 17–21 yr
|}
</div>
Immediately after the eruption enamel is covered by a specific film: Nasmyth's membrane or 'enamel cuticle', structure of embryological origin is composed of keratin which gives rise to the enamel organ.
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 the formation of keratin, as Vitamin C is for collagen. Fluoride, although not a nutrient, is incorporated into the hydroxyapatite crystal of a developing tooth and bones. The dental theory is the low levels of fluoride incorporation and very mild fluorosis makes the tooth more resistant to demineralization and subsequent decay. In situations where calcium, phosphorus, and vitamin D are deficient, the hard structures of a tooth may be less mineralized. A lack of vitamin A can cause a reduction in the amount of enamel formation.
Fluoride ingestion has been noted to delay eruption of teeth for as much as a year or more from the accepted eruption dates since the initial 1940s fluoridation trials. Researchers theorize that the delay is a manifestation of fluoride's depressing impact on thyroid hormones. The delay in eruption has been suggested as the reason for the apparent difference in decay among the youngest children. Fluoride ingestion during tooth development can lead to a permanent condition known as fluorosis with varying levels of severity, the result of fluoride's interference with the normal osteoblast development.
Undiagnosed and untreated celiac disease often causes dental enamel defects and can be the only manifestation of the disease, in absence of gastrointestinal symptoms or malabsorption signs.
Bisphenol A (BPA) is a hormone-disrupting chemical that has been implicated in having negative effects on human health, including, but not limited to, fetal development. As shown in animal studies which mimic human enamel, the mother's consumption of products with BPA during pregnancy can lead to the child's tooth development being obstructed. Those children are shown to be prone to incisor and first molar hypomineralization, a weakened state of the enamel. Additionally, it is most important for mother's to avoid BPA during pregnancy, but also avoid BPA-use in the child's products up to five months of age.
Developmental disturbances
The absence of third molars is very common, occurring in 20–23% of the population, followed in prevalence by the second premolar and lateral incisor.
Anodontia is a complete lack of tooth development. It is rare, most often occurring in a condition called hypohidrotic ectodermal dysplasia.
Hypodontia is a lack of some tooth development (not including third molars). It is one of the most common developmental abnormalities, affecting 3.5–8.0% of the population. Hypodontia is often associated with the absence of a dental lamina, which is vulnerable to environmental forces like infection and chemotherapy medications. It is also associated with many syndromes, such as Down syndrome and Crouzon syndrome.
Hyperdontia is the development of extraneous teeth. It occurs in 1–3% of Caucasians and is more frequent in Asians. About 86% of these cases involve a single extra tooth in the mouth, most commonly found in the maxilla, where the incisors are located. Hyperdontia is believed to be associated with an excess of dental lamina.
Dilaceration is an abnormal bend found on a tooth, and is nearly always associated with trauma that moves the developing tooth bud. As a tooth is forming, a force can move the tooth from its original position, leaving the rest of the tooth to form at an abnormal angle. Cysts or tumors adjacent to a tooth bud are forces known to cause dilaceration, as are primary (baby) teeth pushed upward by trauma into the gingiva where it moves the tooth bud of the permanent tooth.
Enamel hypoplasia or hypomineralization is a defect of the teeth caused by a disturbance in the formation of the organic enamel matrix, clinically visible as enamel defects. It may be caused by nutritional factors,
Some systemic conditions may cause delayed tooth development, such as nutritional factors, endocrine disorders (hypothyroidism, hypopituitarism, hypoparathyroidism, pseudohypoparathyroidism), undiagnosed and untreated celiac disease, anemia, prematurity, low birth weight, renal failure, heavy metal intoxication or tobacco smoke, among others. Teeth affected by regional odontodysplasia nevAmelogenesis imperfecta is an autosomal dominant disease characterized by a defect in dental enamel formation. Teeth are often free of enamel, small, misshapen, and tinted brown. The cause of these deformities is due to a mutation in enamel in expression. Dental patients with this disease should be especially cautious and visit their dentist frequently.
Natal and neonatal teeth are an anomaly that involves teeth erupting in a newborn infant's mouth earlier than usual. The incidence ranges from 1:2,000 to 1:3,500 births. Natal teeth are more frequent, approximately three times more common than neonatal teeth. Some authors reported a higher prevalence in females than males. The most common location is the mandibular region of the central incisors. Natal teeth and neonatal teeth are associated with genetics, developmental abnormalities and certain recognized syndromes. Additional names for this condition include precocious dentition, baby teeth, and milk teeth.
See also
- Polyphyodont
- Tooth regeneration
- Animal tooth development
References
Additional references
- The American Academy of Periodontology. "Oral Health Information for the Public". Retrieved April 10, 2014.
- The American Dental Association. . Retrieved April 10, 2014.
- The American Dental Hygiene Association. "Nutritional Factors in Tooth Development" . Retrieved December 10, 2005.
- The American Dental Hygiene Association. "Table II. Effects of nutrient deficiencies on tooth development" . Retrieved December 10, 2005.
- Ash, Major M. and Stanley J. Nelson. Wheeler's Dental Anatomy, Physiology, and Occlusion. 8th edition. 2003. .
- Buchheim, Jason. "A Quick Course in Ichthyology". Page accessed January 7, 2006.
- Cate, A.R. Ten. Oral Histology: development, structure, and function. 5th ed. 1998. .
- Caceci, Thomas. Veterinary Histology with subtitle "Digestive System: Oral Cavity". Retrieved December 15, 2005.
- Frandson, R.D. & T.L. Spurgeon, 1992. Anatomy and Physiology of Farm Animals. 5th edition. Philadelphia, Lea & Febiger. .
- Harris, Edward F. Craniofacial Growth and Development. In the section entitled "Tooth Eruption." 2002.
- Health Hawaii. . Retrieved December 12, 2005.
- Johnson, Clarke. "Biology of the Human Dentition". 1998.
- Kahn, Michael A. Basic Oral and Maxillofacial Pathology. Volume 1. 2001.
- Monthly Microscopy Explorations "Exploration of the Month: January 1998".
- Neville, B.W., Douglas Damm, Carl Allen, Jerry Bouquot. Oral & Maxillofacial Pathology. 2nd edition. 2002. .
- Riolo, Michael L. and James K. Avery. Essentials for Orthodontic Practice. 1st edition. 2003. .
- Ross, Michael H., Gordon I. Kaye, and Wojciech Pawlina. Histology: a text and atlas. 4th edition. 2003. .
- Summitt, James B., J. William Robbins, and Richard S. Schwartz. Fundamentals of Operative Dentistry: A Contemporary Approach. 2nd edition. Carol Stream, Illinois, Quintessence Publishing Co, Inc. 2001. .
- University of Southern California School of Dentistry. "The Bell Stage: Image 26". Retrieved December 11, 2005.
- . . Retrieved December 11, 2005.
- University of Texas Medical Branch. "Lab Exercises: Tooth development"
- Williams, Michael E. "Jaws: The early years" . 1992. Page accessed January 7, 2006.
- WebMd. "Dental Health: Your Child's Teeth". Retrieved December 12, 2005.
External links
- Database on the expression of different genes in the developing tooth.