Issue 116 / March - April 2017
Tooth Development: The Remarkable Timing of Events, Molecular and Cellular Interactions
Masud Mahmud Bhaila
At around five weeks of development, two U-shaped areas of
bands of cells form in the human embryoâ€™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
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
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
An astonishing feature during development, not unique to
tooth development, is the predetermination of the fate of every one of these
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.
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.
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 â€˜headâ€™
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.
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 toothâ€™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 toothâ€™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
When considered how complicated all of this is, and how
perfectly it functions, one canâ€™t help but be awed.
Antonio Nanci; Ten Cateâ€™s Oral Histology, Development,
Structure and Function.8th Edition, 2013.
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&John Allan; The Fundamentals of Human Embryology, Student Manual (2nd