ODONTOGENESIS

PRIYANKA. SHETTY

CONTENTS

INTRODUCTION

NEURAL CREST

PRIMARY EPITHELIAL BAND

DENTAL LAMINA

VESTIBULAR LAMINA

EPITHELIAL-MESENCHYMAL INTERACTIONS

GENES EXPRESSED DURING TOOTH DEVELOPMENT

STAGES IN DEV OF TOOTH

ROOT FORMATION

FORMATION OF SUPPORTING TISSUES

CLINICAL IMPLICATIONS

CONCLUSION

RECENT ADVANCES

In human,20 primary and 32 permanent teeth develop from the interaction of

oral epithelial cells and underlying mesenchymal cells.

Each developing tooth grows as an anatomically distinct unit, but the basic

developmental process is similar for all teeth.

INTRODUCTION:

NEURAL CREST

Group of cells-separated from neuroectoderm-capacity to migrate&

differentiate extensively within embryo.

Structures-spinal sensory ganglia, sympathetic neurons, Schwann cells,

pigment cells& meninges.

Avian embryo-crest of neural folds-name

Mammalian embryo-lateral aspect of neural plate.

H&N-imp role.

Differentiate-most of the CT.

CT elsewhere-mesoderm: ‘mesenchyme’.

Head- ‘ectomesenchyme’-origin from neuroectoderm.

Proper migration-essential- dvp of face& teeth.

All the tissues of teeth & supporting app (exc enamel)- dvp

directly from NC.

Depletion prevents proper dvp.

The primitive oral cavity or stomadeum is lined by stratified squamous epithelium called the ORAL ECTODERM.

The oral ectoderm contacts the endoderm of the foregut to form the buccopharyngeal membrane.

At about 27 th day of gestation this membrane ruptures and the primitive oral cavity establishes a connection with the foregut.

Most of the connective tissue cells underlying the oral ectoderm are neural crest or ectomesenchymal in orgin.

These cells are thought to instruct or induce the overlying ectoderm to start tooth development,which begins in anterior portion of what will be future maxilla and mandible and proceeds posteriorly.

PRIMARY EPITHELIAL BAND After 37 days of development, a continuous band of

thickened epithelium forms Roughly horse shoeshaped Each band of epithelium called primary epithelial band gives

rise to DENTAL LAMINA which forms first VESTIBULAR LAMINA A key feature of initiation of tooth development is formation of localized thickenings or placodes within primary epithelial bands.

DENTAL LAMINA:

o o

6 weeks old basal cells of oral ectoderm proliferates

This leads to the formation of DENTAL LAMINA which is a band of epithelium that has invaded the underlying ectomesenchyme along each of horse shoe shaped future dental arches.

Dental lamina primodium for the ectodermal portion of deciduous teeth

A-DENTAL LAMINAB-VESTIBULAR LAMINA

Permanent molars arise from distal extension of dental lamina.Development of first permanent molar is initiated at 4th month in utero.2nd molar at first year after birth3rd molar at 4th or 5th years

The successors of decidous teeth lingual extension of the free end of dental lamina successional lamina and develops from 5th month in utero to tenth month of age

FATE OF DENTAL LAMINA

Total activity of dental lamina period of 5 yrs degenerate . D L may be still active in 3rd molar region after it has disappeared elsewhere.

Remnants persist as epithelial pearls or islands within the jaw as well as in gingiva (Epithelial rests of serre/ Cell rests of Serre)Proliferate odontogenic tumours or cysts

VESTIBULAR LAMINA•Buccal ext of Pri epi band•VESTIBULAR LAMINA OR LIP FURROW BAND.

•Proliferation of vestibular lamina into the ectomesenchyme soon after formation of dental lamina VESTIBULE

•V shaped

•Separates the cheek and lip from tooth bearing areas

EPITHELIAL MESENCHYMAL INTERACTION

GENES EXPRESSED DURING TOOTH DEVELOPMENT

Barx Bar H1 homologue in vertebrates(TF)

Bmp Bone morphogenic proteins(SP)

Dlx Distaless homologue in vertebrae(TF)

Fgf Fibroblast growth factor(SP)

Gli Glioma-associated oncogene homologue.

Hgf Hepatic growth factor(SP)

Lef Lymphoid enhances binding factor(TF)

Lhx Lim-homeobox domain gene(TF)

Msx Msh-like genes in vertebrae(TF)

Otlx Otx-related homeobox gene(TF).

Pax Paired box homeotic gene(TF).

Pitx Transcription factor named for its expression in the pituitary gland

Ptc Patched cell-surface cell-surface receptor for sonic hedgehog(Shh).

Shh Sonic hedgehog(SP).

Slit Homologue to dorsophila slit protein(SP).

Smo Smoothed PTC coreceptor for Shh.

Wnt Wingless homologue in vertebrates.(SP)

TF –transcription factor SP-secretory proteins

INITIATION OF TOOTH DEVELOPMENT

TOOTH PATTERNING

REGIONALISATION OF DENTAL ECTODERM

Initiation of tooth development:

Odontogenesis is first initiated by factors resident in the 1st

arch epithelium influencing ectomesenchyme but with time

this potential is assumed by ectomesenchyme

1. lhx-6 & lhx-7 and lim-homeobox domain gene (transcription factor):

Earliest mesnchymal markers which initiate tooth development. Induced by fgf-8 present in epithelium of 1st brachial arch.

2. pax-9

Tooth initiation & Tooth germ location Induced by fgf-8 & down regulated by BMP2 and BMP4(seen where fgf-8 not

seen).

3. Gli gene

4. Lef-1

1st expressed in dental epithelial thickenings and during bud formation shifts to being expressed in condensing mesenchyme.

5.Shh-have a role in stimulating epithelial cell proliferation.

6. Dlx-1 ,Dlx-2

Regionalisation of dental ectoderm:

Shh is expressed where dental ectoderm is formed.

Wnt is expressed throughout in oral cavity except for presumptive

dental ectoderm where shh is expressed

TOOTH TYPE PATTERNING:Determination of specific tooth types at their

correct positions in the jaws.

In heterodonts, 3 families of shapes:

oIncisiform

oCaniniform

oMolariform

HYPOTHESIS

Odontogenic homeobox code model of dental patterning(Field theory)

Clone theory

ODONTOGENIC HOMEOBOX CODE MODEL (FIELD MODEL) OF DENTAL PATTERNING:

The factors related to tooth shape

reside within the ectomenchyme

in distinct graded and overlapping

fields for each tooth family

CLONE THEORYEach tooth is derived from a clone of ectomesenchymal cells programmed by

epithelium to produce teeth of given pattern.

A The molar clone ectomesenchyme has induced the dental lamina to begin tooth development. The clone and dental lamina progress posteriorly

B When a clone reaches the critical size, a tooth bud is initiated at its center.

C The next tooth bud is not initiated until the progress zone of the clone escapes the influence of a zone of inhibition surrounding the tooth bud

DEVELOPMENTAL STAGES

Continuous process.

Different morphologic ‘stages’-descriptive purposes.

Different sizes& shapes; similar stages of dvp.

Named after shape of EO:

Bud

Cap

Bell

STAGES OF TOOTH DEVELOPMENT

Morphologic StagesDental laminaBud stageCap stageBell stage- earlyBell stage- advancedFormation of enamel and dentin matrix

Physiologic process Initiation Proliferation

Morphodifferentiation Apposition

• Histodifferentiation

TOOTH DEVELOPMENT

A-BUD STAGE

B-CAP STAGE

C-BELL STAGE

D,E-DENTINOGENESIS AND

AMELOGENESIS

F-CROWN FORMATION

G-ROOT FORMATION AND

ERUPTION

H-FUNCTION

TOOTH GERM

Includes all the formative tissues for the entire tooth and its supporting structures.

Three main components:-

Enamel organ - ectodermal component that gives rise to enamel.

Dental papilla - ectomesenchymal component that gives rise to dentin and pulp.

Dental follicle or dental sac - ectomesenchymal component giving rise to

cementum, periodontal ligament, and part of the alveolar socket

BUD STAGE Enamel organ differentiate into round or ovoid swelling

called tooth bud. Enamel organ at this stage consists of: 1.Peripherally located low columnar cells. 2.Centrally located polygonal cells

Epithelium of dental lamina is separated from underlying mesenchyme by a

basement membrane.

Ectomesenchymal condensation occurs in relation to enamel organ.

Ectomesenchymal condensation just below enamel organ is known as dental

papilla. It forms future dentin & pulp.

Ectomesenchymal condensation that surrounds tooth bud & dental papilla is

known as dental sac. It forms future cementum & periodontal ligament

MOLECULAR BASIS:

Msx gene expression induces ectomesnchymal condensation .

BMP4

Induces ectomesenchymal condensation .

Induces Msx.

Induces BMP2 & Shh which helps in

transition from Bud to Cap stage.

CAP STAGE Unequal growths in different parts of the tooth bud leads to cap stage

Shallow invagination on the deep surface of the bud.

Resembles a cap sitting on a ball of condensed ectomesenchyme .

Outer enamel epith

Stellate reticulum

Dental sac

Dental papilla

Inner enamel epith

Dental lamina

OUTER AND INNER ENAMEL EPITHELIUM

The peripheral cells of the cap stage: outer enamel epithelium.

The cells in the concavity of cap becomes tall,columnar : inner enamel

epithelium.

The outer enamel epithelium is separated from the dental sac

Inner enamel epithelium from dental papilla by a delicate basement membrane

Hemidesmosomes

STELLATE RETICULUM

Bw IEE& OEE- polygonal cells- synthesize& secrete GAGs into extracellular

component bw epi.cells.

GAGs-hydrophilic-osmotic pressure-drag water into EO.

Increasing amount of fluid-increases-volume of extracellular compartment.

Central cells-forced apart.

Retain connection with each other through cytoplasmic extensions&

desmosomal attachments: star shaped.

Gives central area cushion-like consistency.

Shock absorber.

Protects delicate enamel-forming cells.

DENTAL PAPILLA Under proliferating epithelium of enamel organ ectomesenchyme

proliferates condenses to form the dental papilla formative organ of

dentin and the primodium of the pulp.

The dental papilla shows active budding of capillaries and mitotic figures

DENTAL SAC

Marginal condensation in the ectomesenchyme surrounding the enamel organ

and dental papilla.

Zone a dense and fibrous layer develops : primitive dental sac.

Cells of dental sac : cementum and periodontal ligament.

TRANSITORY STRUCTURES ENAMEL KNOT

ENAMEL KNOT

They are clusters of non dividng epithelial cells visible in sections of molar cap

stage tooth germ.

Vertical enamel knot : enamel cord

Enamel cord extends to meet OEE : Enamel septum

Each tooth germ has single primary enamel knot at the cap stage and as these

disappears

Secondary enamel knots appear at the tips of future cusps in molars.

ENAMEL CORD & ENAMEL NAVEL

A small depression at the point of meeting- ‘enamel navel’.

Transient structures; disappear before enamel formation.

Function of enamel knot& cord may be- reservoir of dividing cells for the

growing EO.

Fgf-4 & Slit-1: best markers; both primary& sec. knots.

Exact physical role-not yet established.

Current view-E.knot-organization centre- orchestrates cuspal

morphogenesis.

ENAMEL NICHE

Apparent structure in histologic sections

created because the dental lamina is a sheet :

contains a concavity filled with connective

tissue.

Impression that the tooth germ has double

attachment to oral epithelium by 2 separate

strands.

BELL STAGE As the invagination of epithelium deepens and its

margins continue to grow, the enamel organ

assumes a bell stage

EARLY BELL STAGE

Inner enamel epithelium

Outer enamel epithelium

Stratum Intermedium

Stellate reticulum

Cervical loop or zone of

reflexion

Dental Papilla

Dental Sac

INNER ENAMEL EPITHELIUM Single layer of cells-differentiate prior to amelogenesis

into tall columnar cells- ‘ameloblasts’.

4-5 µm in diameter; 40µm high.

Contains nucleus away from basement membrane.

Nucleus/cytoplasmic ratio is high.

high glycogen content.

Cytoplasm contains free ribosomes ,a few RER ,some

mitochondria & few scattered tonofilaments.

Attached to one other by junctional complexes

laterally& to SI by desmosomes.

STRATUM INTERMEDIUM A few layers of squamous cells b/w IEE& OEE.

Closely packed-desmosomes& gap jn.

Desmosomal jn bw SR& IEE.

Cells-well developed cytoplasmic organelles, acid mucopolysaccharides&

glycogen deposits: high mitotic activity.

High activity of alk.ph.

Responsible for enamel formation

STELLATE RETICULUM

Expands further-increased extracellular fluid.

Desmosomal jns-bw-SR,SI& OEE.

Before enamel formation- SR collapses.

Reduces distance bw ameloblasts& nutrient capillaries near OEE.

Then, cells-hardly distinguishable from SI.

This change begins-height of cusp, progresses cervically.

OUTER ENAMEL EPITHELIUM Flatten to a low cuboidal form, centrally

placed nuclei

At the end of bell stage-laid in folds.

Bw folds-DS forms papillae-contain

capillary loops- nutritional supply to

avascular enamel organ

Compensate for loss of nutritional supply

from DP - caused due to form of mineralized

dentin. .

DENTAL PAPILLA Enclosed in the invaginated portion of EO.

Before IEE bigins to produce enamel, peripheral cells of DP- odontoblasts-

organizing influence of EO.

First they assume cuboidal form, then columnar; specific potential for dentin

production.

BM-separating EO& DP- ‘membrana preformativa’

Dental Sac:

Consists of undifferentiated mesenchymal cells & circularly arranged collagen fibrils

around enamel organ & dental papilla.

Collagen fibrils are more in dental sac than dental papilla.

Ramifying nerves & vessels are also seen.

Dvp of root DS differentiate into perio fibres that gets embedded in dvp cementum n alv

bone

Cervical loop or zone of reflexion :

Its region where the inner and outer enamel epithelia meet at the rim of the enamel organ

This is the point where cells continue to divide until tooth attains its full size & which after

crown formation gives rise to epithelial component of root formation.

Dental sac Outer enamel epi Ameloblasts Stellate reticulum Stratum intermedium Odontoblasts Dental papilla Cervial loop

ADVANCED BELL STAGE Characterized by commencement of mineralization & root formation.

Boundary bw IEE& odontoblasts- future DEJ.

Formation of dentin occurs first as a layer along future DEJ.

Begins at cusp tips, proceeds cervically& apically.

After 1st layer of dentin- ameloblasts- enamel- cusp area.

Proceeds coronally& cer

Cervical portion of enamel gives vically, from DEJ towards surface. rise to

HERS.

Outlines future root; responsible for shape, length, size& no. of roots.

BREAK OF DL& CROWN PATTERN DETERMINATION

2 imp events occur in the bell stage:

1 . Dental lamina joining tooth germ to OE fragments, eventually- separates

developing tooth from OE.

Fragmentation-> discrete clusters of epithelial cells- normally degenerate.

Some may persist- epithelial pearls (formerly- glands of Serres)

2. IEE completes its folding, making it possible to recognize the shape of

future crown pattern.

Folding occurs not from growth pressures within DP.

Results from intrinsic growth caused by differential rates of mitotic

divisions within cells of IEE.

Stellate reticulum

Enamel Dentin

OEE

odontoblasts

AMELOGENESIS The cells responsible for amelogenesis are ameloblasts.

LIFE CYCLE OF AMELOBLASTS

Presecretory stage Morphogenic stage

Organizing stage

Secretory stage Formative stage

Post-secretory stage Maturative stage

Protective stage

Desmolytic stage

MORPHOGENIC STAGE

The function of ameloblasts :determination of shape of the tooth.

The IEE interacts with the underlying connective tissue and through

differential growth helps to establish DEJ and thereby determine shape of the

tooth.

The ameloblasts at this stage are low columnar, centrally placed nucleus.

Cytoplasmic organelles are not abundant,the centrioles and golgi apparatus are

at apical part of cytoplasm and mitochondria is evenly distributed through out

the cytoplasm.

ORGANIZING STAGE/DIFFERENTIATION STAGE

The ameloblasts exert organizing influence on dental papilla cells and help in

their differentiation to odontoblasts.

Ameloblasts increase in length about 40 microns and has abundant

cytoplasmic organelles for protein synthesis

Reverse polarity is seen.

It’s a preparation to secretion because organelles are moved to secretory end of

cell which is at the basal region.

The cells also develop intercellular junctions at proximal and distal ends called

proximal and distal terminal bars.

During the terminal phase : dentin formation begins and basal lamina

supporting the ameloblasts layer disintergrates.

Ameloblasts attain secretory function only after a layer of dentin is formed.

This interdependence b/w ameloblasts and odontoblasts is called

RECIPROCAL INDUCTION

FORMATIVE/SECRETORY STAGE

In this stage ameloblasts performs functin of secretion of enamel matrix and partial

mineralisation.

Here they synthesise enamel proteins

In initial stages ameloblasts have flat basal region.

As the enamel matrix is deposited, the ameloblasts move away from dentin side

but a part of distal end of ameloblasts gets trapped in its own matrix and this

conical trapped portion is called tomes process.

After Tomes process is formed ,the secretion of enamel takes place from 2

different sites and is responsible for the rod structure of enamel.

MATURATIVE STAGE

Ameloblasts : helps in the mineralization and maturation of enamel.

Introduce the inorganic material necessary for maturation and also removes

proteins and water to provide space for minerals.

Show morphologic alterations.

Ameloblasts are ruffle ended when they are reabsorbing proteins and water.

Shows slight reduction in height and decrease in volume and organelles content.

The basal plasma membrane of ruffle ended ameloblasts shows a brush border with

many foldings while that of smooth ended ameloblasts is smooth.

The cytoplasm of ameloblasts also has vacoules which contains material resembling

enamel matrix indicating absorptive function of these cells.

Excess synthetic organelles are removed and the remaining organelles are shifted

to the distal end of the cells.

PROTECTIVE STAGE

After the enamel formation is completed the basal plasma membrane of

ameloblasts looses the brush border and become smooth.

They secrete protein : to the surface of newly formed enamel.

Dev hemidesmosomal attachments to these basal lamina structure which help in

holding these firmly to the tooth surface.

Columnar ameloblasts shorten to cuboidal and along with the other collasped

layers of enamel organ forms 2-3 layered stratified epithelium which is termed as

REE.

This reduced enamel epithelium covers the newly formed enamel and protects : till

tooth erupts into the oral cavity .

Helps establishing the dentino gingival junction.

DESMOLYTIC STAGE

In this stage the REE secretes collagenase enzyme which destroys the connective

tissue between oral mucosa & erupting tooth. This facilitates eruption process.

During this stage the REE proliferates and fuses with the oral epithelium to form a

solid plug of epithelial cells.

The central cells of this degenerate to form a canal through which the tooth erupts.

Amelogenesis , the process of formation of enamel involves 2 steps : Matrix

deposition & Mineralization.

ENAMEL MATRIX DEPOSITION:

Enamel formation begins :tips and the incisal edges progresses outwards and cervical.

As matrix deposition progresses ameloblasts move outward away from the matrix.

In the early stages of amelogenesis the enamel matrix consists of 20-30% of proteins and

this protein gradually decreases

Ameloblasts synthesise and secrete enamel matrix which is composed of enamel proteins.

Amelogenin and non amelogenin.

Enamel matrix also contains sulphated glyco conjugates.

After a little thickness of enamel matrix is deposited ameloblasts develop a conical

process at the base which is called Tome’s process.

Enamel secretion takes place through two sites in Tome’s process

1. Interod growth region

2. Rod growth region

Tome’s process is responsible for the rod structure of enamel

MINERALIZATION OF ENAMEL MATRIX

In Immediate partial mineralization.

25-35% of total mineral content is deposited in matrix.

It begins at DEJ where the tuftelin , ameloblastin/enamel proteins are deposited on

layer of dentin.

The initial enamel crystallizes to form a ribbon of minerals perpendicular to

DEJ and the process continues till the entire thickness of enamel matrix secreted.

After nucleation , the ameloblasts deposit matrix rich in amelogenin..

Maturation

Massive reabsorption of matrix protein and water takes place by ameloblasts and

there is rapid growth of crystallites.

Initially amelogenin proteins are absorbed onto specific crystal faces , thus

controlling their growth.

The amelogenin proteins are removed from mineralizing front by proteolytic

cleavage mediated by proteinase enzyme and is reabsorbed by endocytic action of

ameloblasts to bring about crystal growth.

The maturation process starts at DEJ and progresses to the surface similarly it

proceeds from cusp/incisal tip to cervical region.

DENTINOGENESISDentin is formed by cells called odontoblasts that differentiates from

ectomesenchymal cells of dental papille following an organizing influence

that emanates from inner enamel epithelium.

ODONTOBLAST DIFFERENTIATION

The dental papilla cells : small and undifferentiated , a central nucleus and a

few other organelles.

Separated from the inner enamel epithelium by an acellular zone that

contains some fine collagen fibrils

The ectomesenchymal cells adjoining

acellular zone rapidly enlarge and elongate

preodontoblasts first and then

odontoblasts , as their cytoplasm increases

in volume to contain increasing amount of

protein synthesisng organelles.

The acellular zone between the dental

papilla and IEE gradually is eliminated as

odontoblasts differentiate and increase in

size and occupy this zone.

These cells are highly polarised with their

nuclei positioned away from the IEE.

FORMATION OF MANTLE DENTIN

Formation of organic matrix. Odontoblasts differentiate in the preexisting

ground substance of dental papilla and 1st dentin collagen synthesised by

them is deposited in this ground substance.

Von korffs fibres appear. They are type 3 associated collagen fibres.

As odontoblasts increase in size, they produce smaller type 1 collagen

fibrils that orient themselves parallel to the future DEJ.

A layer of mantle predentin appears.

The plasma mem of odontoblasts adjacent to IEE extends stubby process into

extracellular matrix which penetrate and interpose itself b/w cells of IEE to form

enamel spindle.

As odontoblasts forms these process, it also buds off a number of small mem bound

vesicles known as matrix vesicles

The odontoblasts then develops a cell process odontoblast process, which is left

behind in the forming dentin matrix ,as the odontoblast moves away towards the pulp.

The mineral phase first appears within the matrix vesicles as single crystals

seeded by phospholipids present in the vesicle membrane.

The crystals grow and rupture spread as a cluster of crystallites that fuse with

adjacent clusters to form a continuous layer of mineralized matrix .

The deposition of mineral layer lags behind the formation of the organic matrix so

that a layer called predentin is found between the odontoblasts and mineralization

front.

Following mineral seeding , non

collagenous matrix proteins produced

by odontoblasts come into play to

regulate mineral deposition

In this way coronal mantle dentin is

formed in a layer approximately 15-20

micrometer thick onto which primary

dentin is added.

FORMATION OF ROOT DENTIN

The epithelial cells of Hertwig’s root sheath initial differentiation of odontoblasts

that form root dentin.

SECONDARY AND TERTIARY DENTINOGENESIS

Secondary dentin is deposited after root formation is completed and is formed by

the same odontoblasts that formed primary dentin.

Tertiary dentin is deposited at specific site in response to injury by damaged

odontoblasts/replacement cells from pulp.

ROOT FORMATION Begins after enamel& dentin formation has

reached future CEJ.

Enamel organ-imp role-HERS- molds shape of

root& initiates radicular dentin formation.

Cells of IEE& OEE- proliferate as double

layered sheath from cervical loop.

Devoid of SI& SR.

HERS-extends around pulp, bw pulp& DF.

Rim of this HERS- ‘epithelial diaphragm’-

encloses primary apical foramen.

Cells of IEE- remain short, do not form

enamel.

But, induce differentiation of odontoblasts at

periphery of pulp, facing HERS.

Odontoblasts- eventually- dentin.

Degeneration of HERS and formation of cell rests of malassez

Differentiation of cementoblasts from dental sac

Cementum formation

Orientation of periodontal ligament

In case of multirooted teeth, there is

differential growth of epithelial diaphragm

in the form of tongue like extensions which

grow towards each other & fuse causing

division of trunk into two or three roots.

FATE OF HERS

After fragmentation: cells drift away;

positioned in PDL.

Conventional sections-discrete clusters

or islands of epi.cells: ‘cell rests of

Malassez’.

FORMATION OF SUPPORTING TISSUES

The supporting tissues of the tooth form from the dental follicle.

As root sheath fragments ectomesenchymal cells of the dental follicle penetrate

b/w the epithelial fenestrations and become apposed to the newly formed

dentin of the root.

Cells differentiate into cementoblasts.

The cells of periodontal ligament and fibre bundles also differentiate from

dental follicle.

HISTOPHYSIOLOGY

A no. of physiologic growth processes.

Overlap.

Many are continuous through morphologic stages.

Each process-predominate in one stage than other.

Ex.: histodifferentiation characterizes bell stage.

Dental lamina Initiation

Bud stage

Cap stage

Bell stage (early)

Bell stage (advanced) Morphodifferentiation

Formation of enamel

& dentin matrix

Proliferation

Histodifferentiation

Apposition

PHYSIOLOGIC PROCESS

INITIATION

Dental lamina & tooth buds- potential for tooth formation.

Specific cells within DL-potential to form EO of certain teeth by

responding to factors.

Different teeth-initiated at different times.

Requires ectomesenchymal-epithelial interactions.

CLINICAL IMPLICATION:

A lack of initiation results in absence of either single tooth or multiple teeth.

Most frequently the permanent upper lateral incisor ,third molar, and lower second

premolars.

Abnormal initiation may result in development of single or multiple supernumerary

teeth

Genes: Lhx-6 & 7

Fgf-8

Pax-9

Sonic hedgehog

Activin-A

Barx

Bmp

Dlx

Gli

Hgf

Lef

Lhx

Msx

Oflx

Ptc

Pitx

Slit

Smo

wnt

PROLIFERATION

Enhanced proliferative activity bud, cap & bell.

Proliferative growth causes regular changes in size & proportion of

growing tooth germ.

Tooth germ already has potential to become more highly developed.

Genes:o Bmp2,4o Dlx 1-3o EGR 1o FGFso Lef1 o Msx 1& 2o Notch 1 -3o Pax9o RAR-α,β,γo RXR-α,β,γo Syndecano Tenascin TGF-βs

HISTODIFFERENTIATION

Succeeds proliferative phase.

Formative cells-definite morphologic as well as functional changes.

Acquire their functional assignment.

Cells become restricted in their functions.

Differentiate; give up capability of multiplying.

This phase-reaches highest development in bell stage, just preceding formation

of enamel& dentin.

Organizing influence of IEE on mesenchyme- evident in bell stage.

Causes differentiation of adj DP cells-odontoblasts.

With formation of dentin: IEE -> ameloblasts; form enamel opposite to dentin.

Enamel does not form in the absence of dentin.

Dentin formation precedes & essential for enamel formation.

Differentiation of epithelial cells precedes & is essential for differentiation

of odontoblasts.

Clinical implications:

In vitamin A deficiency ameloblasts fail to differentiate ,as a result of which

adjacent mesenchyme fails to differentiate & a atypical dentin known as

osteodentin is formed

Defective histodifferentiation of ameloblasts lead to Amelogenesis Imperfecta

Defective histodifferentiation of odontoblasts results in Dentiinogenesis

imperfecta.

MORPHODIFFERENTIATION Morphologic pattern or basic form & relative size-established-differential growth.

Therefore, morphodifferentiation-impossible without proliferation.

Advanced bell stage - imp stage of morphodiff, in the crown, outlining future DEJ.

DEJ& DCJ- different & characteristic for each type of tooth.

Act as a blueprint pattern.

Enamel, dentin & cementum-in conformity with this pattern.

Therefore- responsible for form& size.

Ex.: size& form of cuspal portion of 1st permanent M- established at birth, before

formation of hard tissues begin.

Genes:

Bmp4

Collagens

Dlxl-3

Lef 1

Msxl

Msx2

Notch1 -3

Pax9

RAR

RXR

Tuftelin

Clinical implications:

Endocrinal disturbances can affect tooth shape only during

this stage.

In hypopitutarism small clinical crown is often mistaken for a

small anatomic crown

Disturbances in morphodifferentiation

Supernumerary cusp or tooth

Twinning

Suppression of parts may occur

Peg or malformed tooth

APPOSITION Deposition of matrix of hard dental structures.

Appositional growth- layer-like deposition of extracellular matrix.

This type of growth is therefore additive.

Fulfillment of plans outlined at histo& morphodiff.

Regular& rhythmic deposition of extra cellular matrix.

Periods of activity& rest- alternatively at definite intervals.

Clinical implications:

Genetic & environmental factors may disturb the normal synthesis & secretion of

organic matrix of enamel leading to condition called enamel hypoplasia.

If organic matter is defective, then enamel or dentin is said to be hypocalcified or

hypomineralised.

Conclusion

Teeth are serially homologous structures, which allow the localization and

quantification of the effects of specific gene mutations. It is possible to determine the

phase of odontogenesis affected by these conditions. These features make tooth

development an important system, to understand the intricate molecular mechanisms

that regulate development.

RECENT ADVANCES:

Ectodysplasin, a recently identified signal molecule in the tumor necrosis factor (TNF) family,

and its receptor Edar mediate signalling between ectodermal compartments in tooth germs. The

genes regulated by the different signals include transcription factors and signal receptors that

regulate the competence of the cells to respond to the next signals, as well as new signals that act

reciprocally and thereby continue the communication between cells and tissues (reviewed by 

Jernvall and Thesleff, 2000; Thesleff and Mikkola, 2002).

The transcription factor c-Myb is involved in the control of cell proliferation, survival and

differentiatiON The expression of c-Myb in both species was strong in the odontoblasts and

ameloblasts at the stage of dentin and enamel production suggesting a possible novel role of c-

Myb during tooth mineralization

Eva Matalova, et al,. Expression and characterization of c-Myb in prenatal odontogenesis

Develop. Growth Differ. (2011) 53, 793–803

Msx1 and Pax9 interact synergistically throughout lower incisor development and affect

multiple signaling pathways that influence incisor size and symmetry and that a combined

reduction of PAX9 and MSX1 gene dosage in humans may increase the risk for orofacial

clefting and oligodontia. Mitsushiro Nakatomi, Xiu-Ping Wang,Darren Key, Jennifer J. Lund

,Annick Turbe-Doan,et al, Genetic interactions between Pax9 and Msx1 regulate lip

development and several stages of tooth morphogenesis Developmental Biology

Volume 340, Issue 2, 15 April 2010, Pages 438–449

Zn affects biological events especially in tooth development, with recent progress uncovering

the roles of the Zn transporter Zip13 in mammalian health and diseases Toshiyuki Fukada, 

Yoshinobu Asada, Kenji Mishima, Shinji Shimoda, Ichiro Saito Slc39a13/Zip13: A Crucial

Zinc Transporter Involved in Tooth Development and Inherited Disorders Journal of

Oral Biosciences Volume 57, Issue 1, Pages 1-44 (February 2015)

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