
Teeth have a dual origin:
◦ Ectodermal;
◦ Mesodermal:
◦ Ectomesenchymal.
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Combine tissue type (neural crest cells +
mesenchyme) is called ectomesenchyme.
In tooth development, an interaction occurs
between oral ectoderm and ectomesenchyme to
initiate the process.
Cellular interactions, between
epithelium+ectomesenchyme:
Formation of dentine, enamel and cementum as
well as crown;
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Morphogenesis is stimulated by molecular
signals that control:
◦ Cell growth;
◦ Migration;
◦ Cell fate and differentiation.
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For every developmental event a complex and
intricate cascade of gene expression take place
to direct the cells to the right place and onto the
proper differentiation pathway;
Many of these pathways all result from epithelialmesenchymal interactions in which essentially
the same molecular mediators are implicated.
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First process to occur during embryogenesis;
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Interaction between developing embryonic cells.
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May also be called morphodifferentiation;
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Development of form and specific tissues;

Results from migration of embryonic cells and inductive
interactions between these cells.
Patterning
Specification of the
embryo through
segmentation;
 Patterning is both a
spatial and temporal event
as exemplified by regional
development of incisors,
canines, premolars, and
molars, which occurs at
different times and involves
the classical processes of
induction, competence, and
differentiation.

Differentiation

Process of specialization
of embryonic cells.

Growth deep within a tissue of organ;

As opposed to appositional growth – growth at
the periphery through the addition of additional
cell layers;
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Initiation;
Proliferation;
Histodifferentiation;
Morphodifferentiation;
Apposition;
Maturation;
Eruption.
An intriguing question is
how dental development is
initiated?
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The newly formed stomadeum is lined by a
primitive two- or three-cell-thick layered
epithelium covering an embryonic connective
tissue that, because neural crest cells have
migrated in it, is termed ectomesenchyme;
The ectomesenchyme consists of a few
spindle-shaped cells separated by a
gelatinous ground substance.
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Formation of primary epithelial thickening,
dental lamina, tooth bud & the cap, bell stage
cannot take place in absence of dentally
active ectomesenchyme which becomes
concentrated in regions of presumptive tooth
development;
Inner epithelium of enamel organ induces
ectomesenchyme of dental papilla to become
orientated towards the intervening basal
lamina and differentiate into odontoblasts.
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Thickening of the
epithelium.
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Primary epithelial band;
Vestibular lamina;
Dental lamina.
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A continuous band of thickened epithelium
forms around the mouth in the presumptive
upper and lower jaws;
This bands are roughly horseshoe shaped and
correspond in position of the future dental
arches of the jaws;
Each band of epithelium quickly gives rise to
two subdivisions:
◦ The vestibular lamina and
◦ The dental lamina just behind it.
Upper epithelial
band
tongue
lower epithelial
band
Upper and lower
epithelial bands
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The formation of these thickened epithelial
bands is the result not so much of increased
proliferative activity within the epeithelium as
of a change in orientation of the mitotic
spindle and clevage plane of dividing cells.
Sagittal section through the head of an embryo.
A. Primary epithelial bands; B. The same structure at higher magnification; C
The change in plane of clevage.
Upper epithelial
band
Lower
Epithelial
band
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The first subdivision of the primary epithelial
band is vestibular lamina;
The vestibule forms as a result of the
proliferation of the vestibular lamina into
ectomesenchyme;
Its cells rapidly enlarge and then degenerate
to form a cleft that becomes the vestibule
between the cheek and tooth-bearing area.
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The other subdivision of the primary
epithelial band is dental lamina;
Dental lamina is located orally to the
vestibular lamina;
Within the dental lamina, continued and
localized proliferative activity leads to the
formation of a series of epithelial outgrowths
into the ectomesenchyme at sites
corresponding to the positions of the future
deciduous teeth.
Dental lamina
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
Vestibular
lamina
Vestibular
proliferation leads
to the formation
of the vestibular
lamina;
Oral proliferation
leads to the
formation of the
dental lamina.
tongue
Vestibular
lamina
Dental
lamina
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Begin localized proliferations;
◦ Early in the medial part - incisors;
◦ Then in the lateral part - canines and molars;
In the upper and lower dental lamina are
formed 10 proliferations;
The process is called “the formation of
tooth bud”
This is the beginning of the tooth
development;
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Teeth develop from two typs of cells:
◦ Oral epithelial cells;
◦ Mesenchymal cells from the dental papilla;
◦ Neural crest cells – ectomesenchymal cells;
Epithelial cells are flat on the surface of the
epithelium and cylindrical immediately
above to the basal lamina;
The underlying ectomesenchymal cells
accumulate around the epithelial
autgrowths.
Flat cells
Cylindrical cells
The controlling signals (BMP-7) in place of the thickened epithelium

The proliferation is:
◦ Multiplication of cells;
◦ Increases the amount of tooth bud;

The proliferation is observed:
◦ In the epithelium;
◦ In the ectomesenchym.

Certain cells of the
basal layer begin to
proliferate at a
more rapid rate
then do the
adjacent cells.
These proliferating
cells contain the
entire growth
potential of the
teeth .
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Dental bud;
Dental cap;
Dental bell.
These terms are discriptive of the morphology but
we have to describe the significant fuctional
changes that occur during development, such as
morphogenesis and histodifferentiation;
Because development is a continuous process,
clear distinction brtween the transition stages is
not possible.
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1. Dental bud;
2. Oral epithelium;
3. Ectomesenchyme.

Histological appearance of different cells
with:
◦ Different form;
◦ Different size;
◦ Different function;
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Than are formed different layers of cells :
◦ In the epithelium;
◦ In the ectomesenchym.
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The differentiated cells shall be arranged
under different layers;
Each layer acquires a separate function;
Each layer takes part in creating the
structures of the tooth, in determining the
shape and size of the tooth.
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Enamel organ - epithelial;
Dental papilla:
◦ Мesenchymal;
◦ Ectomesenchymal;
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Dental follicle:
◦ Мesenchymal;
◦ Ectomesenchymal.
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Proliferation of
epithelial cells;
Mitotic cell
division;
Increasing the
cells number;
Increasing the
size of the cells;
Still no cells
differentiation.
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The bud stage is represented by the first
epithelial incursion into the ectomesenchyme
of the jaw;
The epithelial cells show little if any change in
shape or function;
The supporting ectomesenchymal cells are
packed closely and around the epithelial bud.
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Stem cells involved
in the formation of
the tooth bud;
This is pluripotent
cell capable to
become virtually
any cell.
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At this stage there
is no cell
differentiation;
There is only cell
division and cell
mitotic activity;
The cells are
identical in shape
and size.
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The tooth bud now is
a ball of cells;
The tooth bud grows
rapidly in volume.
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The transition from bud to cap marks the
onset of morphological differences between
tooth germs that give rise to different types
of teeth;
As the epithelial bud continues to proliferate
into the ectomesenchyme, cellular density
increases immediately adjacent to the
epithelial outgrowth;
This process referred to as a condensation of
the ectomesenchyme, results from a local
grouping of cells that have failed to produce
extracellular substance and have thus not
separated from each other.
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As the tooth bud grows larger, it drags along
with it part of the dental lamina;
So from that point on the developing tooth is
tethered to the dental lamina by an extension
called gubernaculum dentis or lateral lamina.
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Separated from ectomesenchyme
factors (red) stimulated epithelial
cells (blue), which in turn cause
the release of others in the
ectomesenchyme (pink);
Immediately the bone
morphogenetic protein (green)
inhibits the further release of
epithelial factors (blue);
This is the starting signal for the
cells differentiation.
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It is the beginning of cellular differentiation;
Differentiated cells are arranged in layers;
The formative elements of the tooth are
already visible:
◦ The epithelial outgrowth, which resemble a cap
sitting on a ball of condensed ectomesenchyme,
is referred as the enamel organ (it will form the
enamel of the tooth);
◦ The ball of condensed ectomesenchymal cells,
called dental papilla, forms the dentin and pulp;
◦ The condensed ectomesenchyme limiting the
dental papilla and encapsulating the enamel
organ – the dental follicle or sac – give rise to the
supporting tissues of the tooth.

Because the enamel
organ sits over the
dental papilla like a
cap, this stage of the
tooth development is
known as the cap
stage.
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The cells that covering the enamel organ are outer dental
(or enamel) epithelium;
The cells, which are covering the recess of the enamel
organ are inner dental epithelium;
The center of the enamel organ is termed the stella
reticulum:
◦ The cells in the center of the enamel organ synthesize
and secrete glycosaminoglycans into the extracellular
compartment between the epithelial cells;
◦ Glycosaminoglycans are hydrophilic and so pull water
into the enamel organ;
◦ The increasing amount of fluid increases the volume of
the extracellular compartement of the enamel organ,
and the central cells are forced apart;
◦ Because they retain connections with each other
through their desmosomal contact, they become star
shaped.

You can see three
separate cell layers :
◦ Outer epithelium – a single
row of cuboidal cells;
◦ Inner epithelium - cuboid
cells adjacent to dental
papilla;
◦ Stellate reticulum -star
shaped cells.They are the
largest volume with large
intercellular spaces.
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Enamel knots – are cluster
of nondividing epithelial
cells;
Enamel cord – enamel
knot is extends between
the inner and outer
epithelia as the enamel
cord;
Enamel niche - spaces
between the epithelium of
the dental lamina and
outer enamel epithelium.

1. Dental lamina
2. Dental follicle
3. Outer enamel
epithelium;
4. Stellate reticulum;
5. Inner enamel
epithelium;
6. Dental papilla;
7. Enamel cord - epithelial
proliferation, which
seemed to divide enamel
organ into two parts;
8. Enamel
9. Blood vessels;
10. Enamel niche;
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11. Permanent tooth bud
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Enamel knots are clusters of nondividing
epithelial cells;
The current view is that the enamel knot
represents an organizational center, which
orchestrates morphogenesis.
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Blue dots are the
boundary between
epithelial and
ectomesenchyme cells;
Red circles and arrows
indicate enamel knot the command center.
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The primary enamel knot is
under the influence of betacatenin;
The progression of a bud in
the cap is done under
mesenchymal incentives that
activate cells from the tip of
the tooth bud to form
enamel knot. This is the
epithelial signaling center.
The enamel knot is an
important regulator of tooth
shape;
Induction of the enamel knot
is required for the transition
from bud to cap;
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Enamel knot is cluster
of nondividing
epithelial cells.
If the enamel knot be
removed, the tooth is
not developing.
Enamel knot - the expression of growth factors

Each tooth germ has a single primary enamel
knot and enamel cord at the cap stage, and
as these disappear, secondary enamel knots
appear at the tip of the future cusps in
molars.
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Localized group of cells in the enamel organ;
Enamel cord be located under the outer
enamel epithelium;
It directs and binds to enamel knot;
The function of the enamel cord is obviously
associated with the enamel knot.
Enamel cord
Enamel
knot

This structure is
created by the plane
of section cutting
through a curved
lateral lamina so
that mesenchyme
appears to be
surrounded by
dental epithelium.
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
Continued growth of the tooth germ leads to
the next stage – bell stage, so called because
the enamel organ comes to resemble a bell as
the undersurface of the epithelial cap
deepens;
During this stage, the tooth crown assumes
its final shape (morphodifferentiation);
The cells that will be making the hard tissues
of the crown (ameloblasts and odontoblasts)
acquire their distinctive phenotype
(histodifferentiation).
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At the periphery of the enamel organ the cells
assume a low cuboidal shape and form the
outer dental epithelium;
The cells bordering on the dental papilla
assume a short columnar shape – inner dental
epithelium;
The star-shaped cells forms stellate
reticulum;
In the bell stage, some epithelial cells
between the inner dental epithelium and the
stellate reticulum differentiate into a layer
called the stratum intermedium.
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Represents enlargement of the overall size of the tooth germ and
deepening of its under surface;
Cells at the center secrete an acid mucopolysaccharide into the
extracellular space between the epithelial cells covering the germ,
(drawing in of the water cause enlargement of germ);
A zone of stretched but interconnected cells (stellate reticulum)
produced at center of the germ;
Epithelial cells:
◦ Next to the papilla develop into an enamel-producing layer of
cells (inner dental epithelium);
◦ Along leading edge of germ form the outer dental epithelium
(dental cuticle).
◦ The transition zone between outer and inner dental epithelia
forms the cervical loop.
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
This layer cover enamel organ;
The cells are cuboidal shape;
They are connected to dental lamina;
The function of this cell layer is to transport
products from dental follicle to enamel
organ and to limit the growth impulses of
enamel organ.
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In the early bell stage they have short
columnar shape;
The cells become tall and columnar;
The cells are located directly above the
basement membrane, which separates them
from the cells of the dental papilla;
They have highly developed intracellular
organelles;
At this stage they receive nutrients from the
dental papilla;
Cell nucleus is large and positioned above
the basement membrane.
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
These cells are called "pre ameloblasts”
The functions are:
◦ They are differentiated for protein synthesis;
◦ They are preparing for secretory function;
◦ They stimulate the underlying ectomesenchyme
of the dental papilla;
◦ They produce and secrete the enamel;
◦ They determine the shape of the dental crown.
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
The star-shaped cells are conected to each
other, to the cells of the outer dental
epithelium, and to the stratum intermedium
by attachment plaques known as
desmosomes;
Their cytoplasm contains all of the usual
organelles, but these are distributed sparsely;
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
This layer provides a space for the
development of enamel;
It transports nutrients and incentives for the
ameloblasts;
In the wide intercellular space they stored the
nutrients and water;
There takes place transformation of the
different substances.
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The cells of stratum intermedium are
connected to each other and to the cells of
the stellate reticulum and inner epithelium
also by desmosomes;
There are openings between the cells;
These cells can to be further differentiate into
the cells of the neighboring layers;
This is the reason this layer is called the
germinative layer.
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
First, the dental lamina (and lateral lamina)
joining the tooth germ to the oral epithelium
breaks up into discret islands of epithelial
cells, thus separating the developing tooth
from the oral epithelium;
Second, the inner dental epithelium
completes its folding, making it possible to
recognize the shape of the future crown
pattern of the tooth.
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
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Fragmentation of the dental lamina results in
the formation of discrete clusters of epithelial
cells that normally degenerate, but some may
persist and are given the name of epithelial
pearls;
These may form small cysts (eruption cysts)
and delayed eruption;
May give rise to odontoma;
Or may be activated to form supernumerary
teeth.



The region where the inner and outer dental
epithelium meet at the rim of the enamel
organ is known as the zone of reflexion or
“cervical loop”;
This point is where the cells continue to
divide until the tooth crown attains its full
size and which, after crown formation, gives
rise to epithelial component of root
formation;
Later epithelial cells of the cervical loop
proliferate to form a double layer of cells
known as Hertwig`s epithelial root sheath.
Cervical
loops
Cervical loop



Hertwig's epithelial root sheath (frequently
abbreviated as "HERS") is a proliferation of
epithelial cells located at the cervical loop of
the enamel organ in a developing tooth.
Hertwig's epithelial root sheath initiates the
formation of dentin in the root of a tooth by
causing the differentiation of odontoblasts
from the dental papilla.
The root sheath will further dictate whether
the tooth will have single or multiple roots.
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

It stimulates the ectomesenchyme of the
dental papilla to differentiation;
It simulates the ectomesenchyme of the
dental follicle to differentiation;
It contains information on the number, size
and shape of the dental root.
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

So far, only the initial development of the decidious
(or primary) dentition has been described;
The permanent dentition also arise from the dental
lamina;
The tooth germs that gives rise to the permanent
incisors, canines, and premolars form as a result of
further proliferative activity within the dental
lamina at its deepest extremity;
This increased activity leads to the formation of
another tooth bud on the lingual aspect of the
deciduous tooth germ, which remains dormant for
some time;



They have not deciduous predecessors, so
their tooth germs do not originate in the
same way;
The dental lamina burrows posteriorly
beneath the lining epithelium of the oral
mucosa into the ectomesenchyme;
This backward extention successively form
the tooth germs of the first, second , and
third molars.
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
The cessation of mitotic division within cells of the
inner dental epithelium determinise the shape of a
tooth;
When the tooth germ is growing rapidly during the
cap to bell stage, cell division occurs throughout
the inner dental epithelium;
Division ceases at a particular point because the
cells are beginning to differentiate and assume
their eventual function of producing enamel;
The point at which inner epithelial cell
differentiation first occurs represents the site of
future cusp development, or the growth center.
The zone of cell devision is indicated by the brekened area in
the inner dental epithelium, and the zone where cells have
differentiated by the white area.


The determination of specific tooth types at
their correct positions in the jaws is referred
to as patterning of the dentition;
Two hypothetical models have been proposed
to explain how these different shapes are
determined, and evidence exist tu support
both:
◦ The first is the field model;
◦ The second is the clone model.

The field model proposes that the factors
responsible for tooth shape reside within the
ectomesenchyme in distinct but graded field
for each tooth family;



There is a "incisal field" responsible for dental
shape of the incisors;
It is concentrated in the central incisal area;
The stimulation strongly reduced at the end
of the field.
Presumptive
incisor mesenchyme
Incisal field
Molar
field

The clone model proposes that each tooth
class is derived from a clone of
ectomesenchymal cells programmed by
epithelium to produce teeth of a given
pattern;
Clone theory
A. The molar clon has induced the dental lamina to begin tooth
development. At its posterior border the clone and dental lamina grow
posteriorly by means of progress zona.
B. B. When a clone reaches the critical size, a tooth bud is initiated at its
center. A zone of inhibition surrounds the tooth bud.
C. The next tooth bud is not initiated until the progress zone of the clone
has escaped its influence.

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


The dental papilla is separated from the enamel
organ by a basement membrane;
The cells of the dental papilla appear as
undifferentiated ectomesenchymal cells, having an
uncomplicated structures with all the usual
organelles;
Blood vessels appear early in the dental papilla,
initially in the central region along with nerve fibers
associated with these vessels;
The vessels bring nutrition to the rapidly growing
organ;
As the papilla grows, smaller vessels are also seen
in the periphery of the area, bringing nutrition to
the elongating odontoblasts and ameloblasts.
Dental
papille

The ectomesenchyme of the dental papilla
forms:
◦ Preodontoblasts in the early bell stage;
◦ Odontoblasts in the late bell stage;
◦ The papilla cells are believed to be significant in
furthering enamel organ bud formation into the cap
and bell stage;
◦ This cell density is maintained as the enamel organ
grows.

Dental papilla gives rise to the dentin and
dental pulp;
-The dental follicle is distinguished clearly
from the dental papilla in that many more
collagen fibrils occupy the extracellular
spaces between the follicular fibroblasts;
-These generally are oriented circulary
around the dental organ and dental papilla;
-Clusters of blood vessels are found
ramifying around the tooth germ in the
dental follicle adjasent to the outer dental
epithelium
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Dental follicle is dental sac with its enclosed
developing tooth.
It gives rise to three important entities:
cementoblasts, osteoblasts, and fibroblasts.
Cementoblasts form the cementum;
Osteoblasts form alveolar bone;
Fibroblasts form periodontal ligaments which
connect teeth to the alveolar bone;
The dental follicle is formed partly from cells
at the base of the dental papilla that flatten
and migrate to enclose the whole of tooth
germ.
Dental
follicle



Dental follicle brings nutrition to the
enamel organ and dental papilla;
It limits their growth impulses;
After stimulation of the Herwig’s epithelial
root sheath dental follicle forms cement,
periodontium and alveolar bone.

Enamel organ:
◦ Forms enamel;
◦ Furthered dental papilla and dental follicle;

Dental papilla:
◦ Forms dentin and dental pulp;

Dental follicle:
◦ Forms cement, periodontium and alveolar bone.