Synthesis of teeth

The word "Odontogenesis" comes from Ancient Greek language as two combined sources as follows :

1- Prefix : "odonto", means "tooth". In Greek words, "odous" (ὀδούς). It is used in English biological and medical terminology as refering to teeth.

2- Suffix : "genesis", means origin, birth, producing. In Greek words, "genesis" (γένεσις). It is used in English biological and medical terminology as refering to organic synthesis, formation from the first stages.  

• Epithelial cells.

The oral epithelium, from which enamel organ rises, this epithelium has cells that differentiate later into ameloblasts which are responsible for producing enamel, the outer layer of the tooth crown.

• Mesenchymal cells.

They form dental papilla and dental follicle. Dental papilla gives rise to dental pulp and dentin while dental follicle gives rise to periodontium. These cells, dental mesenchymal stem cells (DMSCs) in particular, are known for being pivotal for tissue regeneration and can differentiate into various cell types involved in tooth formation.

• Signaling molecules.

The orchestarting elements of odontogenesis process, acting as the messengers for regulating cell proliferation, differentiation and apoptosis in the developing tooth. They are presented as signaling pathways including Wnt, Hedgehog (Hh), Fibroblasts growth factors (FGFs), Bone morphogenetic proteins (BMPs) and Notch, with each pathway serving a specific aspect of tooth formation.

In order to form a fully developed tooth, 6 main stages take place respectively as follows, with each of them being characterized by distinct but overlapping morphological changes and cellular differentiations.

1- Initiation 

2- Bud

3- Cap

4- Bell

5- Apposition 

5- Maturation

Information resources

• Concluded from Google knowledge graph, the scientific content released by scientific web platforms including Sciencedirect, Masarykova univerzita, NIH, Nature, Company of Biologists Journals, Mustansiriya University, SpringerLink, and others.
• Last edition by Gemini searching tools aid on 7 September 2025, for the previous resources based content; Delaying mention of Epithelial Rests of Malassez later in the research as it's a feature appears after tooth development, not among first stages, and statement that stages of the process include 6 main stages instead of previous content 5 stages based on previous resources.

According to the writings of Sarah McKarnon and Laura Gartshore, by the side of TeachMe Anatomy platform, in updation of May 20, 2024; initiation stage begins at 6th week in utero by the ectomesenchymal cells which are thought to be derived from neural crest cell population, accumulating below oral epithelium. 

Oral epithelium then proliferates down to ectomesenchyme to form primary epithelial band. During the 7th week in utero, PEB starts to differentiate into vestibular lamina that forms oral vestibule, and dental lamina that forms teeth. Later Gemini updates on 8 September 2025 specify initiation correct timing to be from 6th to 7th week. 

According to Gemini resources collected by writer for updation of 10 September 2025, the bud stage of tooth development begins around the 8th week of intrauterine life. It is marked by the localized growth of the dental lamina, an ectodermal band, which produces ten rounded or ovoid epithelial swellings in each jaw. These swellings are the first evidence of the enamel organ, the future tooth.

During this stage, a key event is the active proliferation and condensation of the ectomesenchyme, which is the tissue surrounding the epithelial bud. This condensation, which is derived from neural crest cells, begins to differentiate into two important structures: the dental papilla, located directly beneath the epithelial bud, and the dental sac, which encloses the entire developing structure. While these components are not yet clearly separated, their formation is crucial for the continued development of the tooth germ in the later cap and bell stages.

The previous paragraph was a corrected paragraph for the conclusion of writers reading the publishing of Mustansiriyah University, its scientific content release among web, by lecturer Noor Natik, Odontogenesis second stage topic, and National Library of Medicine scientific web platform; Bud stage starts the initiation of tooth germ development in the 8th week of intrauterine life when growth cells rise from dental lamina and proliferate as round or ovoid swellings at ten different points in each jaw (upper & lower), these swellings present enamel organs (buds) primordials. During which, proliferation of dental lamina epithelium has poorly morphodifferentiated and histodifferentiated condensation, and is faster than that of adjacent ectomesenchymal cells. Bud has more RNA, higher oxidative enzyme activity, and lower glycogen content than other overlying oral epithelium. By looking at histological features and changes of bud stage, we find that enamel organ is marked by central polygonal and peripherally located low columnar cells, separated from the adjacent ectomesenchyme by basement membrane. Tooth bud and its surrounding ectomesenchyme undergo mitosis leading to ectomesenchymal condensation due to the increased mitotic activity and migration of neural crest cells into the area. The ectomesenchymal consendation immediately subjacent to enamel organ is called dental papilla while the ectomesenchymal consendation surrounding bud and dental papilla is called dental sac, and they both become more well defined as enamel organ grows into cap and bell shapes.

A review for previous conclusion among investigations of Gemini for 10 September 2025 updation; states the following brief correction points :  

• The bud stage starts around the 8th week for the 20 baby teeth, not all teeth.
• The surrounding ectomesenchymal cells (future dental papilla) grow faster than the epithelial cells forming the bud.
• The formation of the dental papilla and dental sac is due to increased local cell division, not just the migration of neural crest cells.
• The dental papilla and sac are only starting to form in the bud stage and don't become clearly defined until the later cap stage.

A brief conclusion for the publishing of Mustansiriyah University, its scientific content release among web, by lecturer Noor Natik stating that The cap stage marks a significant progression in tooth morphogenesis, characterized by the invagination of the deeper surface of the enamel organ, forming a distinctive cap-shaped structure. This stage initiates the histodifferentiation of the enamel organ into the outer dental epithelium and the inner dental epithelium, which will later contribute to tooth formation. Within the central portion of the enamel organ, a greater distinction of cells becomes apparent. As the stage progresses, the intercellular spaces between these cells widen due to the accumulation of glycosaminoglycans, creating a star-shaped appearance for the cells, which remain connected by desmosomes. This resulting tissue is known as the stellate reticulum, although its full development occurs in the subsequent bell stage. While the cells of the outer enamel epithelium remain cuboidal, the inner enamel epithelial cells undergo a transformation, becoming more columnar. This change is accompanied by an increase in RNA content, as well as hydrolytic and oxidative enzyme activity, preparing them for future amelogenesis. Concurrently, the adjacent ectomesenchymal cells continue to proliferate, surrounding the enamel organ and forming what will become the dental papilla and dental follicle.

The early development stages put light on three fundamental transitory structures that may be observed, each with a unique, temporary role as follows :-

1- Enamel Knot which is a localized, non-proliferative mass of cells in the center of the inner dental epithelium. Initially thought to outline the future cusp pattern, recent research suggests it functions as a crucial signaling center during tooth development. The cells of the enamel knot produce signaling molecules, such as bone morphogenetic proteins and fibroblast growth factor, before the structure disappears.

2- Enamel Cord which is an extension of the enamel knot that arises as a vertical strand in the early bell stage. It is termed the enamel septum if it extends from the enamel knot to the outer enamel epithelium.

3- Enamel Niche which is an apparent histological structure caused by the sheet-like nature of the dental lamina, which creates a concavity filled with connective tissue. This arrangement can give the false impression that the tooth germ has a double attachment to the oral epithelium.

Dr. Mohamed Morgan overview conclusion on 18 September 2025 about the previous content ending with cap stage article states approval for the released scientific information with consideration for the following brief statement points.

• According to (Ten Cate’s Oral Histology, 9th ed.; Nanci 2017), the primary teeth erupt during infancy while permanent teeth develop into adolescence and early adulthood.
• According to (Nanci 2017; Ten Cate’s Oral Histology), ameloblasts secret enamel organ which is described as highly mineralized tissue covering the crown.
• According to (Ten Cate; Mitsiadis & Graf, Frontiers in Physiology 2009), dental follicle gives rise to specific elements of periodontium including cementum, periodontial ligament and alveolar bone.
• According to (Ten Cate’s Oral Histology, 9th ed.; Avery’s Oral Development & Histology, 4th ed.; Thesleff, Development 2003), initiation stage begins around week 6th - 7th in utero and establishes the earliest epithelial–mesenchymal interactions necessary for tooth formation.
• According to Dr. Morgan knowledge background, bud stage starts for the 20 primary teeth, not all permanent teeth.

Writer's conclusion on 20 September 2025, according to Nanci A (2019) Oral histology: development, structure and  function. 14th Ed Rio de Janeiro: Elsevier, states that this stage is presented by enamel organ when having a bell-like appearance and surrounding dental papilla which in turn becomes dental pulp from this moment on. 

Writer's conclusion according to Faculty of Dentistry Baghdad University scientific release among web for oral histology, lecturer Nada AL-Ghaban, the majority of enamel organ cells during this stage are called stellate reticulum because of their star-shaped appearance. Bell stage is divided into early and late stages, during which tooth crown assumes its final shape since hard tissue cells including ameloblasts and odontoblasts acquire their distinctive phenotypes. This stage is characterized by enamel organ consisting of 4 distinctive cell layers; stellate reticulum SR presenting the majority of enamel organ cells, outer enamel epithelium OEE (cuboidal cells) lying on the periphery of enamel organ, inner enamel epithelium IEE (columnar cells) lying adjacent to dental papilla, and stratum intermedium SI lying between IEE and SR.

Early stage events

- IEE : consists of a single layer of cells that differentiate into columnar cells (ameloblasts), they are attached together laterally by junctional complexes and to SI by desmosomes, and are separated from dental papilla by 1-2 µm cell free zone. These cells are rich in RNA which explains its role in inducing underlying ectomesenchymal cells of the dental papilla to differentiate into odontoblasts then they differentiate into ameloblasts. After crown completion, IEE with OEE together form a structure from cervical loop called Hertwig's epithelial root sheath that guides the formation of tooth root.

- SI : Appears in early bell stage as several layers of flattened cells (squamous cells) between IEE and SR. These cells are closely attached to each other by desmosomes and gab junctions, and characterized by a high degree of alkaline phosphatase enzyme which explains their role in mineralization of enamel during amelogenesis and transporting minerals to and from IEE that differentiates later into ameloblasts.

- SR : They are marked by the star shape which is due to their prominent nuclei and many branching processes. They have alkaline phosphatase, numerous tonofilaments, and low amounts of RNA, glycogen, endoplasmic reticulum and mitochondria. Between them, there are desmosomes and gap junctions with intercellular spaces being fluid filled due to the osmotic effect arising from high concentration of glycos-aminoglycans. Their function is presented in a mechanical protection for the underlying IEE and inducing hydrostatic pressure equilibrium with dental papilla for allowing proliferation pattern of IEE to shape the crown.

Dr. Mohamed Morgan 

Bachelor of Oral and Dental Surgery (B.D.S) Arab Academy for Science, Technology, and Maritime Transport (College of Dentistry).

Membership of the Faculty of Dental Surgery (Royal College of Surgons of England, The United Kingdom) MFDS, RCSE.

Contact info/ MohammedRM_2001@outlook.com

Flow Online Release.

Writer/ Ahmed Mohamed, founder.

Last updated on the 13th of October 2025.