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Tooth Development: The Remarkable Timing of Events, Molecular and Cellular Interactions
Mar 1, 2017

At around five weeks of development, two U-shaped areas of bands of cells form in the human embryo’s developing mouth. These primary epithelial bands form precisely in the positions of the future upper and lower jaws. Each of these bands then subdivide by proliferating and growing into the underlying tissue (called the mesenchyme). The first of these subdivisions forms the zone where the teeth will form (the dental lamina), while the second, which forms in front of the dental lamina, will form the future vestibule of the mouth (the vestibular lamina).

At this time, within these bands, plate-like structures called placodes, mark the positions of future teeth. Proliferation of cells in these areas continue to grow into the underlying mesenchymal tissue while other cells called ectomesynchymal cells begin to assemble around these swellings of cells.

This sets the stage for the development of the teeth. The process can now be divided into the bud, cap, and bell stages. These three stages only describe the shape of the developing tooth during each stage. An innumerable amount of genes and proteins are involved during each of these stages, some of which are yet to be discovered. During these stages, cells transform into other cells by interacting with each other and by various complex molecular signaling pathways.

An astonishing feature during development, not unique to tooth development, is the predetermination of the fate of every one of these countless cells.

The question of what initiates tooth development , and what determines the positions of the teeth in the developing oral cavity, continues to be a compelling one for researchers. As early as the eleventh day of gestation, signs of initiation emerge. To date, over ninety different genes and numerous other signaling molecules, including transcription factors from various cellular families, have been discovered and implicated in the initiation of tooth development. The intricate and complex interactions that occur during these processes are far from being fully understood.

The bud stage: Also referred to as the ectomesenchymal condensation stage, it is characterized by the invasion of epithelium into the surrounding cells (the ectomesenchyme). Proliferation of cells during this stage increases cellular thickness in the region, hence forming a bud-like structure. There are no significant cellular changes during this stage; however there is much activity surrounding the developing tooth during the transition between the bud and cap stages. Nerve fibers begin to enter the dental follicle, which later enter the dental pulp.

The cap stage: The passage from bud to cap stage is marked by the change in cellular form or shape (morphodifferentiation). These cellular changes are also determined and regulated by numerous signals and the expression of specific genes. The differences that occur at this stage also determine the tooth type that will be formed (incisor, canine, or molar).

The tooth bud continues to grow and pulls the dental lamina as it grows. It now appears like a bulge which rests on a conglomerate of ectomesenchymal cells, hence taking the shape of a cap positioned on a ‘head’ of ectomesenchyme.

At this stage, the future structures of the tooth can be distinguished. The ectomesenchymal portion, now called the dental papilla, will give rise to the dentine and pulp (the blood and nerve supply) of the tooth. The portion on the outside of the dental lamina and the cap (called the dental follicle) will give rise to the future supporting structures of the tooth (the bony socket and periodontal ligament). The cells making up this cap, which includes a lining of cells and the cells inside this lining, are called the enamel organ, and will give rise to the tooth enamel. This triad of structures is collectively termed the tooth germ (i.e., a collection of cells that will form the tooth).

During the latter part of the cap stage, cells begin to transform by altering their functions. The core of the enamel organ forms star shaped cells (the stellate, or star-like, reticulum). This occurs by a process whereby cells produce and discharge a hydrophilic protein which in turn increases water content between cells, thus separating them while they maintain links with each other, giving them the starry appearance.

Around this time a structure called the enamel knot arrives. It is thought to be the coordinating center for tooth cusp shape. It appears and disappears at different stages of development.

In the midst of the cellular changes taking place, clusters of blood vessels begin to penetrate the dental papilla, precisely in the positions of the future roots. It is thought that the blood vessels and nerves also play a role in the initiation of tooth development.

The bell stage: As the growth of the tooth germ proceeds, the inner portion deepens and it begins to bear resemblance to a bell. It is in the course of this stage that the tooth takes on its final shape (its crown form). In addition, the cells which will be responsible for the formation of the tooth’s enamel and dentine form at this stage.

The cells which make up the enamel organ begin to change their form, including their shape and size, while their function changes according to the role they are destined to perform. The cells interact with each other in an astonishingly coordinated way as they induce one cell to differentiate into another at precise stages of formation. Two distinct layers of cells form in this way, which are then separated by an intermediate layer. The outer layer of cells begins to manufacture and secrete the organic components which will later form mature mineralized enamel (ameloblasts), while the inner cellular layer will begin to manufacture and secrete substances which will be the building blocks for the formation of mature dentine (odontoblasts). At the point where the inner and outer cell layers meet at the edge of the bell, the cells continue to proliferate up to the time that the crown size is completed. Once this is complete, the cells then generate the cellular constituents for tooth root development.

By the end of bell stage, the developing tooth is separated from its original attachment to the surface of the developing oral cavity, and is now housed in its own developing crypt.

During the latter part of this stage, an offshoot of tissue forms on the tongue and palate facing the side of the developing tooth. These offshoots are the tooth buds of the future permanent teeth.

The subsequent maturation and mineralization of the tooth’s enamel and dentine are separate areas of study which are indeed as complex and intricate as one can imagine.

This exceedingly complex, orchestrated work of art, albeit simplified for the reader, must occur in harmony with the growth of other structures including the face, tongue, and jaws. The subsequent events that must take place for the appearance of the teeth is yet another area to be studied. This process is exquisitely timed with respect to development and function.

When considered how complicated all of this is, and how perfectly it functions, one can’t help but be awed.


  • Antonio Nanci; Ten Cate’s Oral Histology, Development, Structure and Function.8th Edition, 2013.
  • Beverly Kramer &John Allan; The Fundamentals of Human Embryology, Student Manual (2nd Edition), 2010.