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Development of tooth

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• The primitive oral cavity, or stomodeum, is lined by stratified squamous epithelium called the oral ectoderm

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

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• Membrane ruptures at about 27^th day of gestation.
• Most of the connective tissue cells underlying the oral ectoderm are of neural crest or ectomesenchyme in origin.

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• 2- 3 weeks after the rupture of buccopharyngeal membrane (about 6 weeks), certain areas of basal cells of oral ectoderm proliferate rapidly, leading to the formation of primary epithelial band

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• Continuous plate of odontogenic epithelium roughly horse shoe shaped corresponds in position to the future dental arches of upper and lower jaws.

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At about 7^th week, they quickly divide into

• Dental Lamina
• Vestibular lamina

Coronal section through the anterior portion of developing head A- the positions of vestibular and dental lamina B- the 2 lamina at higher magnification

Sagittal section through the head of an embryo A . The thickened epithelium of primary epithelial band . B- the same at high magnification C- Schematic representation of the change in plane of cleavage during formation of the band and subsequently of the dental lamina

Dental lamina

Differential proliferation at 10 specific regions of dental lamina of upper and lower dental arches gives rise to ectodermal component of deciduous teeth in each arch.

The dental lamina begins to function at 6^th prenatal week and continues to 5^th year of birth (3^rd molar)

The primordium for ectodermal portion of the deciduous teeth.

• Later permanent successors develop from the lingual extensions called Successional Lamina.
• Permanent molars develop from the distal extension of dental lamina called Accessional Lamina

permanent 1^st molar : 4^th month IU

permanent 2^nd molar : 1yr after birth

permanent 3^rd molar : 4 or 5 yrs

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Fate of dental lamina

• Cell rests of Serres
• Seen in the connective tissue of gingiva or in the jaw bones

Average period of activity – 5yrs .

It may still be active in 3^rd molar region after it has disappeared elsewhere.

Odontogenic cysts and tumours

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Vestibular lamina

• Labial and buccal to the dental lamina in each dental arch, another epithelial thickening develops independently
• Vestibular Lamina also termed as lip furrow band
• Subsequently hollows and form the oral vestibule between the alveolar portion of the jaws and the lips and cheeks.

Developmental stages

Bud Stage

Cap stage

As the tooth bud continues to proliferate, it does not grow uniformly. Unequal growth of different parts of the tooth bud leads to the cap stage

Outer enamel epithelium(OEE) –peripheral cuboidal cells covering convexity of cap

Inner enamel epithelium (IEE) –tall columnar cells in the concavity of the cap

OEE separated from dental sac and IEE from dental papilla by a delicate basement membrane

• Stellate reticulum : are polygonal cells located in the centre of the epithelial enamel organ between IEE and OEE
• These cells synthesize and secrete glycosaminoglycan's into the extracellular compartment between the cells . Being hydrophilic water gets pulled into the enamel organ.
• Cells gets forced apart but they retain their connection through desmosomal contact – Star shaped
• Hence called Stellate Reticulum

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At the same time a vertical extension of the enamel knot, called the Enamel Cord occurs.

When the enamel cord extends to meet the outer enamel epithelium – Enamel Septum – dividing the stellate reticulum into 2 parts

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Outer enamel epithelium at the point of meeting shows a small depression – Enamel Navel

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Enamel niche: apparent structure in histologic section.

A section through it creates an impression that tooth germ has a double attachment to oral epithelium

Cells in the center of enamel organ are densely packed and form Enamel Knot. The knot project in part towards the dental papilla

• These are temporary structures that disappear before enamel formation begins.
• Enamel knot and cord act as reservoir of dividing cells for the growing enamel organ.
• Enamel knot acts as a signalling centre – many important growth factors are expressed by the cells of enamel knot – play an important part in determining the shape of the tooth.

• Dental papilla : under the organising influence of the proliferating epithelium of enamel organ, the ectomesenchyme partially enclosed by the invaginated portion of the IEE proliferates and condenses to form the dental papilla- formative organ of dentin and primordium of pulp.
• Dental sac/follicle : marginal condensation of the ectomesenchyme surrounding the enamel organ and dental papilla that becomes denser and more fibrous - primitive dental sac

Enamel organ of cap stage

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1) Inner enamel ep

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2) Outer enamel ep

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3) Cervical loop

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4) Stellate reticulum

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5) Enamel knot

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6) Enamel cord

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7) Enamel navel

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transient structure

during cap stage

http://www.iob.uio.no/studier/undervisning/histologi/index.php

Enamel Organ of Cap Stage

Bell Stage

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• As the invagination of epithelium deepens, enamel organ assumes a bell shape
• Dental lamina that was providing attachment to the oral ectoderm undergoes degeneration and enamel organ looses its connection to the oral ectoderm.
• Crown shape is determined in this stage. The determination of crown shape is under the control of genes and their signalling molecules
• Histodifferentiation and morphodifferentiation takes place in this stage

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IEE

• Short columnar shape with centrally placed nucleus and cytoplasm contains free ribosomes, few RER, mitochondria, tonofilaments and Golgi apparatus situated towards the stratum intermedium.

Stratum intermedium

• Some epithelial cells between IEE and Stellate reticulum differentiate into a layer called Stratum intermedium.
• Exceptionally high Alkaline Phosphatase activity
• IEE and Stratum intermedium work synergistically as a single functional unit in the formation of enamel.

Stellate reticulum

• The stellate reticulum expands further, mainly by an increase in the amount of intercellular fluid.
• Before enamel formation begins, the stellate reticulum collapses, reducing the distance between the centrally situated ameloblasts and the nutrient capillaries near the outer enamel epithelium.
• Its cells then are hardly distinguishable from those of the stratum intermedium. This change begins at the height of the cusp or the incisal edge and progresses cervically

Advanced Bell Stage

• At the sites of the future cusp tips, where a layer of dentin will first appear, mitotic activity ceases, and the short columnar cells of the inner enamel epithelium elongate and reverse polarity, becoming taller with their nuclei aligned adjacent to the stratum intermedium and the Golgi complex facing the dental papilla.
• IEE reverses polarity - apical portions of ameloblasts now face the papilla.
• As these morphologic changes occur in the cells of the inner enamel epithelium, changes also occur within the adjacent dental papilla. The undifferentiated ectomesenchymal cells increase rapidly in size and ultimately differentiate into odontoblasts, the dentin-forming cells. This increase in size of the papillary cells eliminates the acellular zone between the dental papilla and the inner enamel epithelium.

Hard Tissue Formation

Outer enamel epithelium

• The cells of the outer enamel epithelium flatten to a low cuboidal form with high nuclear/cytoplasmic ratio. Cytoplasm contains few ribosomes, RER, mitochondria and few tonofiaments. Junctional complexes join adjacent cells.
• At the end of the bell stage, the formerly smooth surface of the outer enamel epithelium is laid in folds. Between the folds the adjacent mesenchyme of the dental sac forms papillae that contain capillary loops and thus provide a rich nutritional supply for the intense metabolic activity of the avascular enamel organ.
• This would adequately compensate the loss of nutritional supply from dental papilla owing to the formation of mineralized dentin.

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Dental lamina

• The dental lamina is seen to extend lingually and is termed successional dental lamina as it gives rise to enamel organs of permanent successors of deciduous teeth (permanent incisors, canines and premolars)
• The enamel organs of deciduous teeth in the bell stage show successional lamina and their permanent successor teeth in the bud stage

Dental papilla

• The dental papilla is enclosed in the invaginated portion of the enamel organ. It is separated from the enamel organ by a basal lamina from which a mass of fine aperiodic fibrils extends into the an acellular zone. These fibres corresponds to the lamina fibro reticularis of the basal lamina and there the 1^st secreted enamel proteins accumulate.
• The dental papilla is referred to as the pulp when the 1^st calcified matrix appears at the cuspal tip of the bell stage

• The dental papilla ultimately gives rise to dental pulp, once the dentin formation begins at the cuspal tip of the bell stage tooth germ.
• The basement membrane that separates the enamel organ and the dental papilla just prior to dentin formation is called the membrana preformativa.

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Dental sac

• Distinguished by – more collagen fibrils in extracellular spaces.
• Fibres are arranged circularly around dental organ and dental papilla.
• With the development of the root, the fibers of the dental sac differentiate into the periodontal fibers that become embedded in the developing cementum and alveolar bone.

Nerve and Vascular Supply

Blood vessels are seen in dental follicle . They extend into dental papilla .the vessels entering the papilla are clustered into groups that coincide with the position where roots will form.

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Enamel organ is avascular, though heavy concentration of vessels in the follicle exists adjacent to the OEE

Pioneer nerve fibres approach the tooth during the bud-to-cap stage. Their target is the dental follicle , nerve fibres ramify and form a rich plexus around the tooth germ in that structure

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The innervation of developing teeth is concerned with the sensory innervation of the future periodontal ligament and pulp.

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At no time do nerve fibres enter the enamel organ.

• The odontoblasts, as they differentiate, begin to elaborate the organic matrix of dentin, which ultimately mineralizes. As the organic matrix is deposited, the odontoblasts move toward the centre of the dental papilla, leaving behind a cytoplasmic extension around which dentin is formed. In this way the tubular character of dentin is established.
• Just before the first layer of dentin forms (mantle dentin), differentiating inner enamel epithelium cells (ameloblasts) secrete some enamel proteins, which do not accumulate as a layer. These first proteins, together with other molecules (including growth factors), may play a role in the epithelial-mesenchymal signalling that leads to the terminal differentiation of odontoblasts, possibly by interacting with components of the basal lamina that separates them.
• The enamel-forming cells, the ameloblasts, move away from the dentin, leaving behind an ever-increasing thickness of enamel.

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For these events to take place normally, differentiating odontoblasts must receive signals from differentiating ameloblasts (inner enamel epithelium), and vice versa— an example of Reciprocal Induction.

Source of nutrition

• blood vessels located in the dental papilla and vessels situated along the periphery of the OEE
• When the dentin is formed, it cuts off the papillary source of nutrients, causing a drastic reduction in the amount of nutrients reaching the enamel organ. This reduction occurs when the cells of the inner enamel epithelium are about to actively secrete enamel, and thus the demand for nutrients increases. The demand is satisfied by an apparent collapse of the stellate reticulum and invagination of the outer enamel epithelium by blood vessels lying outside.

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Root Formation

• Begins after enamel and dentin formation has reached the future cementoenamel junction.
• The cervical portion of the enamel organ gives rise to the Epithelial Root Sheath Of Hertwig. The Hertwig’s epithelial root sheath (HERS) outlines the future root and is thus responsible for the shape, length, size, and number of roots

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• HERS molds the shape of the roots and initiate radicular dentin formation
• HERS consists of only IEE and OEE
• The OEE & IEE bend at the future CEJ into a horizontal plane to form Epithelial Diaphragm narrowing the wide cervical opening

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A-Radicular pulp cavity; B- Dentin; C- Dental sac; D-Point at which epithelial root sheath begins to disintegrate; E- Epithelial diaphragm

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• The proliferation of the cells of the epithelial diaphragm is accompanied by the proliferation of the cells of the connective tissues of the pulp, adjacent to the diaphragm
• Differentiation of odontoblasts and formation of dentin follows lengthening of root sheath
• Connective tissue of the dental sac surrounding the root sheath proliferates & invades the continuous double epithelial layer dividing it into network of epithelial strands
• Connective tissue cells come into contact with outer surface of dentin & differentiate into cementoblasts

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In the last stages of the root development, the proliferation of the epithelium in the diaphragm lags behind that of the pulpal connective tissue

The wide apical foramen is reduced first to the width of the diaphragmatic opening itself & later is further narrowed by apposition of dentin & cementum to the apex of the root

• Differential growth of the epithelial diaphragm in the multirooted teeth causes the division of root trunk into 2 or 3 roots

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• Expansion of cervical opening occurs in such a way that long tongue like extensions of the horizontal diaphragm develop

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• Before division of the root trunk occurs, free ends of the horizontal epithelial flaps grow towards each other & fuse

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• The single cervical opening is divided into 2 or 3 openings

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• On the pulpal surface of the dividing epithelial bridges, dentin formation starts

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• On the periphery of each opening, root development follows in the same way as described for single rooted teeth

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Tooth Eruption

Soon after formation of the root is initiated, the tooth begins to erupt.

Formation of supporting tissues

CEMENTUM

As the root sheath fragments, ectomesenchymal cells of the dental follicle

penetrate between the epithelial fenestrations and become apposed to the newly formed dentin of the root & differentiate into cementoblasts

ALVEOLAR BONE

Recent evidence indicates that the bone in which the ligament fiber bundles are embedded also is formed by cells that differentiate from the dental follicle

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PERIODONTAL LIGAMENT

The cells of the periodontal ligament and the fiber bundles also differentiate from the dental follicle

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Summary of tooth development

HISTOPHYSIOLOGY

• Number of physiological growth processes participate in the progressive development of teeth
• Overlap considerably

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INITIATION

• initiation induction requires ectomesenchymal epithelial interaction
• Mechanism of such interaction is not clearly understood

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PROLIFERATION

• Enhanced proliferative activity results in bud ,cap and bell stages of enamel organ
• Causes regular changes in the size and proportion of growing tooth germ

HISTODIFFERENTIATION

• Formative cells of tooth germ undergo definite morphologic as well as functional changes
• Cells give up their capacity to multiply and differentiate- Bell stage

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• Organizing influence of IEE on mesenchyme is evident & cause differentiation of adjacent cells of dental papilla into odontoblasts

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• With dentin formation cells of IEE differentiate into ameloblast and enamel matrix is formed

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MORPHODIFFERENTIATION

• Basic form and relative size of future tooth is established
• Advanced bell stage
• Outlining future dentinoenamel junction
• DEJ and dentinocemental junction act as blue print in conformity with which enamel, dentin and cementum are deposited

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APPOSITION

• Deposition of the matrix of the hard dental structures
• Regular and rhythmic deposition of the extra cellular matrix

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MORPHOLOGICAL

1. Dental lamina
2. Bud stage
3. Cap stage
4. Early bell stage
5. Advanced bell stage
6. Formation of enamel and dentin

matrix

PHYSIOLOGICAL

Initiation

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Proliferation

Histodifferentiation

Morphodifferentiation

Apposition

CLINICAL CONSIDERATIONS

DEFECT IN INITIATION

ANODONTIA

FUSION/GEMINATION

OLIGODONTIA

SUPERNUMERARY TEETH

ABNORMAL LOCATION – DERMOID CYST OR TERATOMA OF OVARY

DEFECTS IN HISTODIFFERENTIATION

DENTINIGENESIS IMPERFECTA

ATYPICAL DENTIN FORMATION – DENTIN DYSPLASIA

DEFECTS IN MORPHODIFFERENTIATION

TALON CUSP (SUPERNUMERARY CUSP)

HUTCHINSONS INCISOR

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MACRODONTIA

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SUPERNUMERARY ROOTS

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DENS IN DENTE

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PEG LATERALS

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DEFECTS IN APPOSITION

ENAMEL HYPOPLASIA

INTRINSIC STAINING

CONCRESCENCE

HYPODONTIA

Few known mutations

• MSX-1 and PAX-9 : Oligodontia
• REIG gene (mouse ortholog is PITX-2 OR Otlx-2) : Reiger’s syndrome

ECTOPIC TOOTH FORMATION

Ectopic expression of Lef-1 in the oral epithelium

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Msx-1,Msx-2,Alx-3-anterior regions of first arch

Dlx-1,Dlx-2,Barx-1- posterior regions of arch

Msx-1,Msx-2,Dlx-2 – overlap in canine region

CONCLUSION

• Tooth development is a complex process controlled by a number of epithelial ectomesenchymal interactions involving various genes and proteins

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• So it is important for us to have a clear knowledge of different stages of tooth development so as to predict the role of various external and internal agents that could potentially produce malformations and prevent them from occurring.

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• Many developmental questions are still unanswered

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Thank you!