human tooth development human tooth development 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. radiograph of lower right (from left to right) third, second, and first molars in different stages of development. 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. 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. overview histologic slide showing a tooth bud. a: enamel organ b: dental papilla c: dental follicle the tooth germ is an aggregation of cells that eventually forms a 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 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. 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 entities: 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 developing the periodontal ligament which connect teeth to the alveolar bone through cementum. 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. maxillary (upper) teeth primary teeth centralincisor lateralincisor canine firstmolar secondmolar initial calcification 14 wk i.u. 16 wk i.u. 17 wk i.u. 15.5 wk i.u. 19 wk i.u. crown completed 1.5 mo 2.5 mo 9 mo 6 mo 11 mo root completed 1.5 yr 2 yr 3.25 yr 2.5 yr 3 yr mandibular (lower) teeth initial calcification 14 wk i.u. 16 wk i.u. 17 wk i.u. 15.5 wk i.u. 18 wk i.u. crown completed 2.5 mo 3 mo 9 mo 5.5 mo 10 mo root completed 1.5 yr 1.5 yr 3.25 yr 2.5 yr 3 yr maxillary (upper) teeth permanent teeth centralincisor lateralincisor canine firstpremolar secondpremolar firstmolar secondmolar thirdmolar 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 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 root completed 10 yr 11 yr 13–15 yr 12–13 yr 12–14 yr 9–10 yr 14–16 yr 18–25 yr mandibular (lower) teeth 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 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 root completed 9 yr 10 yr 12–14 yr 12–13 yr 13–14 yr 9–10 yr 14–15 yr 18–25 yr stages histology of important stages of tooth development 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. initiation stage one of the earliest signs in the formation of a tooth that can be seen microscopically is the distinction between the vestibular lamina and the dental lamina. it occurs in the sixth to seventh week of the embryonic life. the dental lamina connects the developing tooth bud to the epithelial layer of the mouth for a significant time. this is regarded as the initiation stage. bud stage the bud stage is characterized by the appearance of a tooth bud without a clear arrangement of cells. the stage technically begins once epithelial cells proliferate into the 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. 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 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. histologic slide of tooth in early bell stage. note cell organization. bell stage the bell stage is known for the histodifferentiation and morphodifferentiation that takes place. the dental organ is bell-shaped during this stage, and the majority of its cells are called stellate reticulum because of their star-shaped appearance. the bell stage is divided into the early bell stage and the late bell stage. cells on the periphery of the enamel organ separate into four important layers. cuboidal cells on the periphery of the dental organ are known as outer enamel epithelium (oee). the columnar cells of the enamel organ adjacent to the enamel papilla are known as inner enamel epithelium (iee). the cells between the iee and the stellate reticulum form a layer known as the stratum intermedium. the rim of the enamel organ where the outer and inner enamel epithelium join is called the cervical loop. 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. histologic slide of tooth in late bell stage. note disintegration of dental lamina at top. the crown of the tooth, which is influenced by the shape of the inner enamel epithelium, also takes shape during this stage. throughout the mouth, all teeth undergo this same process; it is still uncertain why teeth form various crown shapes—for instance, incisors versus canines. there are two dominant hypotheses. the "field model" proposes there are components for each type of tooth shape found in the ectomesenchyme during tooth development. the components for particular types of teeth, such as incisors, are localized in one area and dissipate rapidly in different parts of the mouth. thus, for example, the "incisor field" has factors that develop teeth into incisor shape, and this field is concentrated in the central incisor area, but decreases rapidly in the canine area. the other dominant hypothesis, the "clone model", proposes that the epithelium programs a group of ectomesenchymal cells to generate teeth of particular shapes. this group of cells, called a clone, coaxes the dental lamina into tooth development, causing a tooth bud to form. growth of the dental lamina continues in an area called the "progress zone". once the progress zone travels a certain distance from the first tooth bud, a second tooth bud will start to develop. these two models are not necessarily mutually exclusive, nor does widely accepted dental science consider them to be so: it is postulated that both models influence tooth development at different times. other structures that may appear in a developing tooth in this stage are enamel knots, enamel cords, and enamel niche. histologic slide of developing hard tissues. ameloblasts are forming enamel, while odontoblasts are forming dentin. advanced bell stage hard tissues, including enamel and dentin, develop during the next stage of tooth development. this stage is called the crown, or maturation stage, by some researchers. important cellular changes occur at this time. in prior stages, all of the iee cells were dividing to increase the overall size of the tooth bud, but rapid dividing, called mitosis, stops during the crown stage at the location where the cusps of the teeth form. the first mineralized hard tissues form at this location. at the same time, the iee cells change in shape from cuboidal to columnar and become preameloblasts. the nuclei of these cells move closer to the stratum intermedium and away from the dental papilla as they become polarized. histologic slide of tooth. note the tubular appearance of dentin. a: enamel b: dentin the adjacent layer of cells in the dental papilla suddenly increases in size and differentiates into odontoblasts, which are the cells that form dentin. 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