• 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 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

    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
    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
    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
    : 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.

    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

    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.


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