CELL TISSUE INTERACTIONS

It is clear from the existence of regulation and the differing differentiation pathways of cells in
the early embryo, that interactions take place between the cells of the developing embryo.
These interactions provide the developmental integration and fine control to achieve tissue
specific morphogenesis.
Primary induction or interaction occurring early in
development, leading to emergence of three germ layers .

Secondary induction also known as epithelial-mesenchymal

interaction, controls cellular proliferation and differentiation.
In adult life for maintenance of normal functional heterogeity
of the tissues and organs.

TYPES OF INTERACTION

PERMISSIVE INTERACTION
INSTRUCTIVE INTERACTION
They occur later in
Early interactions guiding
development. No specific
uncommitted cells changes
instruction or signal will limit
the cell type of the
the developmental options of
responding tissue, ie. the
the responding tissue, ie there
population becomes
is no restriction .
restricted.
A signal is necessary for
maintaining cell division and
differentiation.
Wessells (1977) proposed four general principles in instructive interaction
In the presence of tissue A, responding tissue B develops in a certain way.
In the absence of tissue A, responding tissue B develops in that way.
In the absence of tissue A, but in the presence of tissue C , tissue B does not develop in
that way.
In the presence of tissue A, a tissue D, which would normally develop differently, is
changed to develop like B.

In early embryo ,interactions

occur only if particular regions
such as organizers or signaling
centres are present.Later as it
matures, interactions occur
between adjacent cell
populations; ie epithelium
&mesenchyme and even later
between adjacent
differentiating tissues.

The distinctly
compartmentalized boundaries
of epithelium and mesenchyme
which would not normally
come in contact ,when apposed
together result in a
differentiation.

These independent
compartments whose origin,
function , morphology and
other biological properties are
so different interact with each
other for developmental
co-existence.

organs

Mesenchyme- Loosely
associated cells
surrounded by a
extracellular matrix
.They are Mesodermal in
origin.

Epithelium- layers of cells

closely adjoined by
specialized membrane
structures. cells are
Ectodermal in origin and
forms lining surface of all

EPITHELIAL MESENCHYMAL
INTERACTION

There are a specific subset of embryonic tissue

interaction involving epithelium and mesenchyme.
They provide a mechanism for co ordinating and
fine tuning the development for example
mitotic rate,differentiative ability etc of two
tissues which are key for successful morphogenesis.
During the development of gut, the epithelium is the source,
which gives an inductive signal via growth factors to the
mesenchyme which responds to the stimulus . Epithelial cells
produce enzymes associated with the relevant species and it
influences the underlying mesenchyme and confer its
morphogenetic properties.
A similar effect my be seen in the early stages of formation of
the base of the skull, where the neuroepithelium by placing
specific molecules in the basal lamina, can halt the migration
of subjacent mesenchymal cells and initiate their
differentiation along chondrogenic pathway.
Thus there temporally reciprocal sigalling
between epithelium and mesenchyme,
with time RECIPROCAL INTERACTIONS

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Epithelial mesenchyme
interaction in
odontogenesis

The mammalian tooth development was experimentally used by embryologists as a useful model
since it seems to comply well with the general principles of tissue interactions .
The ectomesenchymal cells and stomatodeal epithelial cells gradually acquire higher levels of
differentiation and end up as secretory odontoblasts and ameloblasts, it is SEQUENTIAL and
RECIPROCAL in nature.

Stages in
tooth
development

It was established that both epithelium and mesenchyme are required for tooth development
to occur by separating the tissues using trypsin and recombining them to bring about
odontogenesis .
Tooth development is induced by EPITHELIUM around embryonic day 10.
Transplantation experiments carried out on autografts , proved for the first time that
enamel organ was responsible for the differentiation of odontoblasts.
Any CNC cell population can support tooth development which
when recombined with oral ectoderm. Thus the major effect of
oral ectoderm is to limit tooth to mouth

HOW DO THESE SIGNALS

COMMUNICATE.?

1st hypothesis

A chemical substance produced by cell diffuses across the n

arrow intervening space between to be taken up and cause
induction in the other cell layer.

A porous membrane(pore size0.6um) was placed in between separated late bell stage
epithelium and mesenchyme.It was recombined and cultured.
As molecules could easily diffuse even through a pore size <0.2um,the absence of
differentiation argues against 1st hypothesis.
2nd hypothesis
Induction is triggered by direct cell-to-cell contact
but was ruled out since this mechanism could not be proved in vivo.

 3rd hypothesis
This suggested the presence of an extracellular matrix, which is a thin layer situated between
epithelium and mesenchyme. This hypothesis is the most accepted one as :1.
2.

Lathyrogens (drugs that inhibit cross linking of collagen)when added to tissue culture,
tooth differentiation was inhibited.
Isolated pieces of ECM produced histological signs of differentiation in IEE cells.

Extracellular matrix was thus thought to be

responsible for causing induction in EMI.
Extra cellular matrix itself is a product of epith
Ilial and mesechymal cells.
(Vaino et al,1994)

There are varoius results obtained on the basis of certain

experiments carried out in accordance with the importance
of extracellular matrix in induction process.
Firstly ,
inhibits
lathyrogens + tissue culture
cross
linking of collagen

interrupts the
differentiation of tooth germ.
.

Secondly , isolated pieces of extracellular matrix will

produce histological signs of differentiation in internal
enamel epithelial cells of the enamel organ.

A considerable number of genes and growth fators are

expressed during each stages of tooth development .

For example

Bone morphogenic proteins ,nerve

factors Fibroblats gf ,sonic hedge hog
stages of
and transforming factors

Epidermal growth factors

development

different
development

bell stage of

Enamel organ or dental

papilae???
There are various experiments conducted to differentiate the
importance of enamel organ and dental papillae
A) In induction of histogenisis and morphogenesis , in both
the terms the result indicated that in the cap stage of tooth
development the principal organizer is the dental lamina .
Culturing dental papilae mesenchyme
normal tooth
development
With epithe;ium from developing foot pad
Enamel organ of a tooth is cultured with
development
mesenchyme from developing foot pad

no tooth

B) In determining the shape of tooth experiments involve

separating and recombining enamel organ and papilla at
the cap stage

Incisor enamel organ+

tooth
molar papilla

Molar enamel organ +

tooth
incisor papilla

molariform

incisiform

Studies have been conducted to differtiate on the

recombination of mammalian epithelium and mesenchyme
in different combinations before the signs of tooth
development occur.
Neural crest materials are only obtained from developing
brain cells (sources of future dental papillae N.C.) on
combining with oral or limb epithelium. Premigratory neural
crest will form tooth only on assoiciation with oral
epithelium.
Experiments conducted to prove field theory
( Local environment provide signals important for initiation
and development of teeth)
Developing first mandibular dental lamina
and the surrounding mesenchyme,( at the cap stage)
cultured in a totally different site away from the
jaws ---continues to develop normally and the
remaining second and third molars also develop

Experiments conducted to prove -- clone theory

(series of related structures can form by budding from a single
precursor)
the differences between the individual structure results from the
increasing age of the tooth budding region as it grows distally from
the tooth .thus it proves that the successful of tooth development
depends on complex reciprocal interaction b/w the dental epithelium
and underlying mesenchyme .
initially ,
1st brachial arch epithelium
neural crest
ectomesenchyme
(instructive capacity)
Later,
(transferred)
Bioactive
molecules
mesenchyme
epithelium of non first
(helping factors)
arch
Transcription
origin tooth germ of
factors
appropriate
Growth factors
tissues and shape
cytokinines

There are certain biological mechanisms that help in

determining the development of tooth formation.
The activation of non hox homeobox genes is of crucial
importance at this time .they contain DNA binding proteins
that regulate gene transcription thus controlling
development of tooth structure .
The homeobox plays an important role in production of
molecules for morphogenesis such as growth factors,
factors controlling cell division ,cell adhesion etc. the
importance can be diagrammatically expressed in the
following way:

The evidence to support the importance of such molecules

in initiating the tooth development can be seen in
transgenic mice where an absence of the homeobox gene,
Msx-1 results in tooth development being arrested in bud
stage .the early mesenchyme isolated from the overlying
epithelium can still continue to develop in tissue culture if
molecules such as BMPs and FGFs are added to the
medium.

In addition to the development of tooth at correct site its

important for tooth to develop with the correct shape too.
(Such incisors in the front and molars at the back.)

DETERMINATYION OF SHAPE

In some animals

Hetrodont:a
ll teeth of
different
shape

Homodont :all
tooth of same
shape

Incisiform:dental
pappilae of an incisor
tooth germ+dental
organ of a molar
tooth germ dental
organ shapes incisor

Caniniform

Molariform:molar
dental pappilae
can cause a dental
organ to become
molariform

CROWN PATTERN OF TOOTH

During Bell stage
internal dental

fluid filled sac with the

epithelium as a partition

across its middle

Stellate reticulam cells

are seperated from

each other by ground

substances