for dental students

2. Introduction
Embryonic origin of dental tissue
Primary epithelial band
 Initiation – Dental lamina
- Fate od dental lamina
– Vestibular Lamina
– Clinical Aspects
Proliferation – Bud stage
– Cap stage
– Clinical Aspects
 Histodifferentiation/ – Early bell stage
Morphogenesis
Advanced bell stage – Clinical Aspects
Apposition – Clinical Aspects

3. Crown maturation
Root formation – Root sheath
- Single root
- Multiple root
- Clinical Aspects
Development of supporting structures
Development of primary and permanent teeth
 Successional and accessional tooth development
 Establishment of oral and aboral axis
 Control of tooth germ position
 Patterning of dentition
Conclusion

4. Introduction
• In human beings, 20 deciduous and 32 permanent teeth develop from the
interaction between the oral epithelium cells and the underlying mesenchymal cells.
• The basic developmental process is similar for all teeth but each evolving tooth
develops as an anatomically distinct unit.
• Teeth are unique and unusual organs in many respects.
• In humans they are nonessential, but in all other animal species they are
absolutely required for survival.
• In addition, their preservation in the fossil record makes them indispensable for
understanding mammalian and in particular human evolution.

5. • Thus the tooth organ represents an advantageous system in which to study not only
its own development but also developmental pathways, in general.
• The five major conserved signaling pathways that intervene in these events are
(1) bone morphogenetic protein (BMP),
(2) fibroblast growth factor, (FgF),
(3) sonic hedgehog (Shh),
(4) Wingless-related integration site (Wnt),
(5) Ectodysplasin A (Eda).

6. GROWTH FACTORS
These were primarily important for signaling of various developmental steps.
The behaviour of another cell in its vicinity or an autocrine affect would be
initiated by one cell through signaling of these growth factors molecules per se.
Thus, these signaling molecules were vital in development.
MAJOR GROWTH FACTOR PRESENT IN TOOTH DEVELOPMENT
Fibroblast Growth Factor (FGF)
Epidermal Growth Factor (EGF)
Transforming Growth Factor (TGF)
Bone Morphogenetic Protein (BMP) – Member of TGF-β
Platelet Derived Growth Factor (PDGF)

7. Fibroblast Growth Factor
 FGF belongs to a large family of heparin binding proteins that were
known to mediate the growth and differentiation of cells from a wide
variety of developmental origins.
 At the time of odontogenic initiation this expression becomes restricted to
the area of the presumptive dental epithelium and persists until the
beginning of bud stage.
 An important role by this factor was found in the differentiation of
ameloblasts as FGF4 and FGF9 were revealed in the inner enamel
epithelium .
 Various evidences relevant to role of FGF have greater significance in
understanding the value of its presence in tooth development

8. Epidermal Growth Factor
 EGF is very important for signaling and synergistic effect of different
factors.
 It has got a vivid role in development of an embryo and highly
essential for interaction between key players of development .
 EGF signaling would be responsible for activation of major tissues like
submandibular glands and further studies in this direction could hold
better results .
 Another suggestion was that EGF and EGFR has specific values in
development. Evidences pointed to the fact that EGF would be co-
relating and important factor in development

9. Transforming Growth factor
 TGF and its receptor Edar were involved in multiple signaling systems
during developmental regulative mechanisms .
 Another idea was that TGF-β and Shh signaling from Hertwig's
epithelial root sheath induces the differentiation of root progenitor cells
and thereby has a direct control in modulating and transforming the
formation of odontoblasts.
 Several studies had evidences for contribution of this factor in
development .
 It was also established that during tooth morphogenesis, TGF-β
signaling controls odontoblast maturation and dentin formation .

10. Bone Morphogenetic Proteins
 Large family of dimeric proteins within the TGF beta super family of
cytokines consist of BMPs.
 Wide range of signaling functions that mediate tissue interactions during
development were mediated through this factor.
 For example, the expression pattern of BMP-4 shifts from the epithelium
to condensing dental mesenchyme at the same time when the inductive
potential for odontogenesis shifts from epithelium to mesenchyme.
 It has a vital significance in modulating TGF signaling between tissues
that lead to differentiation of odontoblasts.
 Evidences revealed that BMP had enormous significance in governing
future teeth characteristics

11. Genetic factors
 The size, shape and structure of teeth and also position of teeth were
determined by genes present in the region.
 Majority of the genes were central regulations of development that are
associated with interactions between cells.
 The pathway includes genes encoding the actual signals, their receptors and
mediators of signaling pathways and transcription factors.
 These genes primarily were associated with major interactions and process
involved in development and maturation of teeth namely Msx gene, Pax
gene, Shh gene, Wnt/ beta – Catenin signaling, Cbfa-1 gene

12. Muscle Segment Homeobox
 This homeobox gene was the first gene demonstrated which was essential
for development of tooth in mice.
 The significance of the gene was recognized in the fact that Msx1 creates
modulation to cap stage through various stages of ectomesenchyme
proliferation and condensation .
 Mice defects for Msx 1 and 2 results in failure of epithelial mesenchymal
interactions and defects like anodontia or hypodontia and cleft palate occur.

13. Muscle Segment Homeobox
 In humans, the cap stage of primary tooth in development has expression
of Msx-1 restricted to the dental papilla mesenchyme .
 It was suggested that they regulate dental mesenchyme proliferation The
anomalous expression of Msx-2 was reserved to mesenchyme of tooth
forming sites

14. Pax Gene
 This paired homeobox gene is a nine-member family and plays a key role
during embryogenesis and the significant contribution of this multifaceted
gene was unveiled during its expression in some stem cells and mature cells
of adult.
 It also functions as transcription factor present in mesenchyme.
 Zhao M et al., investigated the presence of Pax in dental mesenchyme and
during arrest of tooth development .

15. Pax Gene
 Bhatt S et al., has studied upon the anchor laid by this special gene in
governing the signals needed for neural crest differentiation and further
maturation .
 Paixao-Cortes VR et al., extensively examined the potential and presence
in various processes and its structure .
 Several studies by authors investigated the pivotal axis laid down by this
gene in tooth formation and thus agenesis was given supreme importance

16. Sonic Hedgehog
 It was expressed in molar tooth germ and in enamel knot. It spreads
along inner enamel epithelium and implies expression of gene in enamel
knot, a signaling centre.
 Shh pathway was one of the vital cog in embryonic development.
 Evaluative evidences clinched that Shh signaling and variants
supplement the nuances of the development process by implicating that
they predominantly determines the growth of facial structures especially
palate which was further depending upon epithelial mesenchymal
interactions .

17. Sonic Hedgehog
 Relation between FGF and Shh signaling was studied for better realization
of the pathway . Further, this was substantiated by Yu JC et al., and Li Z et
al., attributing to the nature and presence of the gene in various steps of
development .
 The signaling was found to be a sequential process mediated by epithelial-
mesenchymal interactions

18. Wnt/ beta – Catenin Signaling Pathway
 In a recent study, the data suggested that the Wnt signaling
was present throughout dental epithelium and mesenchyme
during tooth development, confirming its role in overall process .
 They were strongly indicated in odontoblast differentiation.
 Another viewpoint was that this pathway was the front runner in
tooth initiation, and this was highly essential for later processes
and regulates other factors during development

19. Core Binding Factor Subunit Alpha-1 gene
 Master gene for tooth development and also required for
odontoblasts differentiation.
 It is now called Runt-related transcription factor 2 (Runx-2).
 The gene encodes a transcription factor for osteoblast and
odontoblast differentiation, including cementoblasts’ differentiation
and proliferation.
 Much significance has been attached to their presence expressed
during tooth root development .
 The expression might be different in dental follicle from which
cementum was derived to the level in dental papilla

20. Role of Extracellular Molecules (Ecm)
 ECM was present in interactions in the morphogenesis and differentiation of
developing tooth including budding of oral epithelium and condensation of
neural crest cells around the bud.
 In the developing tooth, the epithelial basement membrane contains several
types of collagen and also laminin and fibronectin.
 It was also imperative to understand that ECM may give rise to signaling
events with the help of growth-factor-like receptors that were present in
laminin, tenascin and others .

21. Role of Extracellular Molecules (Ecm)
 The interactions mediated by the basement membrane were regulated by
the differentiation of mesenchymal cells into odontoblasts .
 The structural components of ECM and components affect cellular structure.
 Also, they were involved in regulation of interactions.
 The first extra cellular matrix molecule to appear during embryonic
development is basement membrane.
 Their function includes mediation of signals for sustained and proper
development.
 By binding to specific matrix receptors on the cell surface, the extracellular
matrix molecules exert their effects on the cells and structural components.

22. Embryonic origin of dental tissue
• The basic histology of mammalian tooth development demonstrates that this process
derives from two principal cell types within the early jaws, epithelium and neural
crest-derived ectomesenchyme.
• The epithelium is ultimately derived from the epiblast of the early embryo, and
mammalian fate mapping studies have suggested that this component of the
developing tooth is derived from ectoderm; however, in other species such as fish
and reptiles teeth can develop within the pharynx from endoderm.
a b

23. c d
• Neural crest cells disperse from the dorsal surface of the neural tube and migrate
extensively throughout the embryo, giving rise to a wide variety of differentiated cell
types.
• Cranial neural crest-derived ectomesenchyme contributes to the formation of
condensed dental mesenchyme at the initial bud stage and subsequently to
formation of the dental papilla and follicle in the developing tooth germ.
• Genetic fate mapping studies have demonstrated a cranial neural crest origin for
odontoblasts, dentin matrix, pulp tissue, cementum, and the periodontal ligament of
mature teeth.

24. TOOTH DEVELOPMENT

25. • At certain points along the dental lamina each representing the location of
one of the 10 mandibular & 10 maxillary teeth, ectodermal cells multiply rapidly &
little knobs that grow into the underlying mesenchyme.
• Each of these little down growths from the dental lamina represents the beginning of
the enamel organ of the tooth bud of a deciduous tooth.
• First to appear are those of anterior mandibular region.
• As the cell proliferation occurs each enamel organ takes a shape that resembles a
cap.

26. • Thus the tooth germ consists of ectodermal component- the enamel organ, the
Ectomesenchymal components- the dental papilla & the dental follicle.
• The enamel is formed from the enamel organ,
the dentin and the pulp from the dental papilla and
the supporting tissues namely the cementum,
periodontal ligament & the alveolar bone from the
dental follicle.

27. Primary Epithelial Band
• The oral ectoderm is neural crest or ectomesenchyme in origin.
• It is lined by stratified squamous epithelium.
• The initial oral cavity develops after the rupture of the buccopharyngeal
membrane at the fourth week of intrauterine life.
Schematic
representation of
the early oral
cavity showing the
internal surface of
the upper and
lower jaws and
illustrating the
position of the
primary.

28. • The primary epithelial band forms as a result of a change in orientation of the plane of
the dividing cells

29. • The formation of these thickened epithelial bands is the result not so much of increased
proliferative activity within the epithelium as it is a change in orientation of the mitotic
spindle and cleavage plane of dividing cells.

30. Dental lamina
• At the sixth week of gestation period, certain areas of basal cells of the oral ectoderm
proliferate more rapidly than the adjacent cells. The primary epithelial band forms two
subdivisions called the dental lamina and the vestibular lamina.
• The dental lamina is a band of epithelium that has
invaded the underlying ectomesenchyme
along both the horseshoe-shaped
future dental arches.
The primary epithelial band
divides into two processes,
the vestibular lamina and the
dental lamina (embryo sixth week,
CR length 10 mm)

31. • Formation and growth of placodes is believed to involve the transcription factor p63,
tumor necrosis factor (TNF), and ectodysplasin (Eda), among others.
• Defects in these pathways lead to ectodermal dysplasia's characterized by missing
teeth (oligodontia) and misshapen teeth.
• On the other hand, over activation of the Eda receptor
leads to extra teeth with aberrant morphology.
• Inhibition of Wnt signaling by overexpressing the Wnt inhibitor Dkk1 prevents the
formation of tooth placodes and the initiation of teeth fails, pointing to Wnt as the
most upstream signal and the inducer of tooth initiation.

32. • On the anterior aspect of the down-growing dental lamina, continued and localized
proliferative activity leads to the formation of a series of epithelial outgrowths into
the mesenchyme at sites corresponding to the positions of the future deciduous
teeth.
• Ectomesenchymal cells accumulate around these outgrowths.
• From this point, tooth development proceeds in three stages: the bud, cap, and bell.
• These terms are descriptive of the morphology of the developing tooth germ but do
not describe the significant functional changes that occur during development, such
as morphogenesis and histodifferentiation.

33. Fate of Dental Lamina
• After initiation of tooth development, the dental lamina degenerates.
• Total functional activity period of the dental lamina is around five years.
• Sometimes it takes more than five years, when the initiation of tooth development is
delayed.
• After functional activity, the remnants of the dental lamina may persist in the jaw or
gingiva in the form of islands or epithelial pearls.
• These are known as cell rest of Serres.

34. CLINICAL
CONSIDERATIONS

35. ANODONTIA
•Anodontia, also called anodontia vera, is a
rare genetic disorder characterized by the
congenital absence of
all primary or permanent teeth
It is of following types
1. Complete anodontia/ total anodontia
2. Partial anodontia/ sub-Total anodontia
Forms
1. True anodontia
2. Psuedo anodontia
3. False anodontia
COMPLETE
PARTIAL

36. SUPERNUMERARY TEETH
Hyperdontia is the condition of having supernumerary teeth, or
teeth which appear in addition to the regular number of teeth
Supernumerary teeth can be classified by shape and by
position. The shapes include:
• Supplemental(where the tooth has a normal shape for
the teeth in that series);
• Tuberculate (also called "barrel shaped");
• Conical (also called "peg shaped");
• Compound odontome (multiple small tooth-like
forms);
• Complex odontome (a disorganized mass of dental
tissue)
When classified by position, a supernumerary tooth may be
referred to as a mesiodens, a paramolar, or a distomolar.

37. Vestibular lamina
• Facial (labial and buccal) to dental lamina another thick band of epithelium develops
in the maxillary and mandibular dental arches.
• It is called as the vestibular lamina or the lip furrow band.
• It develops somewhat later and independently.

38. • If a coronal section through the developing head region of an embryo at 6 weeks of
development is examined, no vestibule or sulcus can be seen between the cheek and tooth-
bearing areas.
• The vestibule forms as a result of the proliferation of the vestibular lamina into the
ectomesenchyme soon after formation of the dental lamina.
• The cells of the vestibular lamina rapidly enlarge and then degenerate to form a cleft that
becomes the vestibule between the cheek and the tooth-bearing area.

39. DEVELOPMENTAL STAGES

40. • These enamel organs represent the tooth bud of deciduous dentition.
• First these enamel organs develop in the mandibular anterior region.
• These enamel organs increase in size, as the cells continue to proliferate.
• They take the shape of a cap with their outer surface towards the oral cavity.
Inside the depression of the enamel organ, that is, inside the cap, the
ectomesenchyme cells increase in number.

41. MORPHOLOGICAL
1. Dental lamina Initiation
2. Bud stage Proliferation
3. Cap stage
4. Early bell stage Histodifferentiation
5. Advanced bell stage Morphodifferentiation
6. Formation of enamel and dentin matrix Apposition
PHYSIOLOGICAL

42. BUD STAGE /
PROLIFERATION
• The epithelium of the tooth bud forms the enamel.
• The epithelial cells do not show any change in shape and
function.
• The supporting ectomesenchymal cells are densely packed
under the lining epithelium and around the epithelial bud.
• The enamel organ of bud stage contains two types of cells.
1. Polygonal cells, which are centrally situated
2. Low columnar cells, which are peripherally situated.

43. • The ectomesenchyme of the enamel portion of the
enamel organ is divided as a result of the increased
mitotic activity.
• The centrally situated cells rapidly divide and grow and
are condensed and form the dental papilla.
• Tooth pulp and dentin are formed from dental papilla.
• The ectomesenchyme that surrounds the tooth bud and
dental papilla forms the dental sac.
• Cementum and periodontal ligament are formed from the
dental sac.

44. CAP STAGE / PROLIFERATION
• The epithelial bud continues to proliferate into the ectomesenchyme.
• Immediately adjacent to the epithelial ingrowth, the cellular density increases.
• This process is known as the condensation of the ectomesenchyme.
• When the embryo is 20 weeks old (180 millimeters), deciduous dentition is at various
stages of development.

45. OUTER & INNER ENAMEL EPITHELIUM
• The cells of the outer enamel epithelium are
cuboidal and cover the convexity of the cap
whereas the cells of the inner enamel
epithelium are tall, columnar and cover the
concavity of the cap.
• Basement membrane separates the inner
enamel epithelium from the dental papilla
and outer enamel epithelium from the dental
sac. Hemi desmosomes anchor the cells to
the basal lamina.

47. STELLATE RETICULUM
• Polygonal cells located between the outer and the inner enamel
epithelium, begin to separate due to water being drawn into the enamel
organ from the surrounding dental papilla
• As a result the polygonal cells become star shaped but maintain contact
with each other by their cytoplasmic process
• As the star shaped cells form a cellular network, they are called the stellate
reticulum

48. • The cells in the center of the enamel organ are densely packed and
form the enamel knot.
• This knot projects toward the underlying dental papilla.

49. • At the same time a vertical extension of the enamel knot, called the enamel cord
occurs

50. • The function of enamel knot & cord
may act as a reservoir of the dividing
cells for the growing enamel organ.
• The enamel knot act as a signaling
centers as many important growth
factors are expressed by the cells of
the enamel knot & thus play an
important role in determining the
shape of the tooth.
• The Ectomesenchymal condensation
i.e the dental papilla & the dental sac
are pronounced during this stage of
dental development.
Cap stage of tooth germ development. The tooth bud of
a deciduous tooth showing invagination of dental papilla
(3) on the inferior aspect of enamel organ (2) giving rise
to cap shape to the tooth germ. Successional lamina (4)
with very early primordium of permanent tooth is
growing posterior to the dental follicle (7). (5) Dental
lamina, (6) Dental sac, 1= Alveolar bone. (H & E x 20).

51. DENTAL PAPILLA
• On the inside of the cap, the Ectomesenchymal cells increase in number.
• The tissue appears more dense than the surrounding mesenchyme and
represents the beginning of the dental papilla.
B = Dental Papilla

52. DENTAL SAC/ DENTAL FOLLICLE
• Surrounding the combined enamel organ or dental papilla, the third part
of the tooth bud forms.
• It is known as dental sac/follicle and it consists of ectomesenchymal cells
and fibres that surrounds the dental papilla and the enamel organ.
C= Dental sac

53. BELL STAGE / HISTODIFFERENTIATION AND
MORPHODIFFERENTIATION
• Due to continued uneven growth of the enamel
organ it acquires a bell shape.
• In bell stage crown shape is determined.
• It was thought that the shape of the crown is due
to pressure exerted by the growing dental papilla
cells on the inner enamel epithelium.
• This pressure however was shown to be
opposed equally by the pressure exerted by fluid
present in the stellate reticulum.
• The folding of enamel organ to cause different
crown shapes is shown to be due to different
rates of mitosis & difference in cell differentiation
time

54. a. Inner enamel epithelium
b. Stratum intermedium
c. Stellate reticulum
d. Outer enamel epithelium
• The development of teeth occurs in various
developmental stages.
• Anterior teeth are at a more advanced stage than
posterior teeth, as anterior teeth erupt earlier the
development of teeth occurs in various
developmental stages.
• Anterior teeth are at a more advanced stage than
posterior teeth, as anterior teeth erupt earlier

55. INNER ENAMEL EPITHELIUM
• The inner enamel epithelium consists of a single
layer of cells that differentiate prior to
amelogenesis into tall columnar cells called
ameloblasts.
• These elongated cells are attached to one another
by junctional complexes laterally & to cells in the
stratum intermedium by desmosomes.
• The cells of the inner enamel epithelium exert a
strong influence on the underlying
mesenchymal cells of the dental papilla, which
later differentiate into odontoblasts.

56. STRATUM INTERMEDIUM
• A few layers of squamous cells form the stratum
intermedium , between the inner enamel
epithelium & the stellate reticulum
• These cells are closely attached by desmosomes
& gap junctions
• This layer seems to be essential to enamel
formation

57. STELLATE RETICULUM
• The stellate reticulum expands further due
to continued accumulation of intra-cellular
fluid
• These star shaped cells, having a large
processes anastomose with those of
adjacent cells
• As the enamel formation starts., the
Stellate reticulum collapses to a narrow
zone thereby reducing the distance
between the outer & inner enamel
epithelium

58. OUTER ENAMEL EPITHELIUM
• The cells of the outer enamel epithelium flatten to
form low cuboidal cells
• The outer enamel epithelium is thrown into folds
which are rich in capillary network, this provides a
source of nutrition for the enamel organ
• Before the inner enamel epithelium begins to
produce enamel. Peripheral cells of the dental
papilla differentiate into odontoblasts
• These cuboidal cells later assumes a columnar
form & produce dentin

59. DENTAL LAMINA
• Dental lamina is seem to extend lingually
and is termed successional dental lamina
as it gives rise to enamel organs of
permanent successors of deciduous teeth
• The enamel organs of deciduous teeth in
the bell stage show successional lamina &
their permanent successor teeth in the bud
stage

60. DENTAL PAPILLA
• The dental papilla is covered by the enamel organ.
• The mesenchymal peripheral cells of the papilla
differentiate into specialized cells called odontoblasts,
which produce dentin.
• First, they are cuboidal-shaped and are then
elongated to become columnar in shape and produce
a thin layer of predentin.
• Thereafter, the inner enamel epithelium produces
enamel.

61. DENTAL SAC
• The dental sac exhibits a circular arrangement of fibres &
resembles a capsule around the enamel organ
• The fibres of the dental sac form the periodontal ligament
fibres that span between the root & the bone
• The junction between the inner enamel epithelium &
odontoblasts outlines the future dentino-enamel junction

62. CLINICAL
CONSIDERATIONS

63. DENTINOGENESIS IMPERFECTA
• Dentinogenesis imperfecta (hereditary
Opalescent Dentin) is a genetic disorder of tooth
development.
• This condition causes teeth to be discolored (most
often a blue-gray or yellow-brown color) and
translucent. Teeth are also weaker than normal,
making them prone to rapid wear, breakage, and
loss.
• These problems can affect both primary (baby)
teeth and permanent teeth.
• This condition is inherited in an autosomal
dominant pattern, which means one copy of the
altered gene in each cell is sufficient to cause the
disorder.

64. ADVANCED BELL STAGE
• Characterized by the commencement of
mineralization & root formation.
• The boundary between the inner enamel
epithelium & odontoblasts outline the
future dentinenamel junction.
• Formation of dentin occurs first as a layer
along the future dentinoenamel junction in
the region of future cusps & proceeds
pulpally & apically.
• After the first layer of dentin is formed, the
ameloblasts lay down enamel over the dentin
in the future incisal & cuspal areas.

65. • The enamel formation then proceeds
coronally & cervically in all the regions from
the dentinoenamel junction toward the
surface.
• The cervical portion of enamel organ gives
rise to Hertwig Epithelial Root Sheath (HERS)
• This HERS outlines the future root & thus
responsible for the size, shape, length &
number of roots.

66. CLINICAL
CONSIDERATIONS

67. HUTCHINSON’SINCISOR
MULBERRY MOLARS

68. FUSION
• The phenomenon of tooth fusion
arises through union of two normally
separated tooth germs, and
depending upon the stage of
development of the teeth at the time
of union, it may be either complete or
incomplete.
• However, fusion can also be the union of
a normal tooth bud to a supernumerary
tooth germ. In these cases, the number
of teeth is fewer if the anomalous tooth is
counted as one tooth.

69. GEMINATION
Gemination arises when two
teeth develop from one tooth
bud and, as a result, the
patient has an extra tooth

70. FORMATION OF ENAMEL & DENTIN MATIX
( APPOSITION)
• Apposition is the deposition of the matrix of the hard enamel structures.
• Appositional growth of the enamel & dentin is a layer like deposition of
an extracellular matrix. This type of growth is therefore additive.
• Appositional growth is characterised by regular & rhythmic deposition of the
extracellular matrix, which is of itself incapable of further growth.

71. CLINICAL
CONSIDERATIONS

72. ENAMEL HYPOPLASIA
Enamel hypoplasia is the defect of the
teeth in which the tooth enamel is hard but
thin and deficient in amount This is
caused by defective enamel matrix
formation with a deficiency in the
cementing substance

73. AMELOGENESIS IMPERFECTA
• Amelogenesis imperfecta presents with
abnormal formation of the enamel or external
layer of teeth. Enamel is composed mostly of
mineral, that is formed and regulated by the
proteins in it. Amelogenesis imperfecta is due to
the malfunction of the proteins in the enamel:
ameloblastin, enamelin, tuftelin, amelogenin
• People afflicted with amelogenesis imperfecta
have teeth with abnormal color: yellow, brown or
grey. The teeth have a higher risk for dental
cavities and are hypersensitive to temperature
changes. This disorder can afflict many number
of teeth.

74. Dens- In- Dente ( DENS
INVAGINATUS)
• Represents a defect of tooth in which a focal
area on the tooth surface is folded or
invaginated pulpally to a variable extent
• Defect in generally localized to a single tooth
& interestingly maxillary lateral incisors are
more commonly affected
• Bilateral involvement is often seen &
sometimes defect can involve multiple teeth
involving the supernumeraries
• In case of pulp involvement with or without
apical pathology, endodontic treatment should
be attempted. However in more severe form
extraction should be done

75. DENS EVAGINATUS
• Dens evaginatus is a condition found in teeth
where the outer surface appears to form an
extra bump or cusp.
• Premolars are more likely to be affected than
any other tooth. This may be seen more
frequently in Asians
• The pulp of the tooth may extend into the dens
evaginatus.
• There is a risk of the dens evaginatus
chipping off in normal function
• Hence this condition requires monitoring as the
tooth can lose its blood and nerve supply as a
result and may need root canal treatment.

76. TALON CUSP
• A talon cusp, also known as an "eagle's
talon", is an extra cusp on an anterior tooth.
• Of all cases, 55% occur on the permanent
maxillary lateral incisor, and 33% occur on
the permanent maxillary central incisor.
They are found rarely in primary teeth
• Whenever the lingual pits are present
restorative treatments should be done to
prevent caries
• When talon cusp interferes with normal
occlusion preventive care should be taken
by performing endodontic treatment

77. • Future crown patterning also occurs in the bell stage, by folding of the inner dental
epithelium.
• Cessation of mitotic activity within the inner dental epithelium determines
the shape of a tooth.
Crown Pattern Determination

79. ROOT FORMATION
SINGLE ROOT

80. MULTIPLE ROOT

81. CLINICAL
CONSIDERATIONS

82. DILACERATION
• Dilaceration refers to an angulation or a sharp
bend or curve anywhere along the root portion
of a tooth
• Condition probably occurs subsequent to trauma
or any other defect of development which alters
the angulation of the tooth germ during root
formation
• Can easily be detected by radiographs
• Care should be taken during extraction since
these teeth are more prone to fracture

83. CONCRESCENCE
Concrescence is a condition of teeth where the
cementum overlying the roots of at least two teeth
join together. The cause can sometimes be attributed
to trauma or crowding of teeth.
Radiographic diagnosis is mandatory before
attempting tooth extraction

84. DEVELOPMENT OF PRIMARY AND PERMANENT TEETH

85. DEVELOPMENT OF SUPPORTING STRUCTURES
PERIODONTAL LIGAMENT

86. ALVEOLAR PROCESS

88. Establishment of Oral–Aboral Axis
LIM-homeobox (Lhx) genes constitute tothat group of gene clusters which are dispersed
outside the homeobox gene clusters and they are transcriptional regulators controlling
pattern formation. Lhx-6 and Lhx-7 have been localized during embryogenesis at high
levels.
Bothare identically distributed in theectomesenchyme and inthemesenchymeadjacentto the
epithelialthickeningswhichconstitutethedentalprimordium.

89.  The expression of Fgf-8 establishes the anteroposterior axis of the first
branchial arch and was shown restricted to the first arch.
 Fgf-8 has been attributed to be regulating the expression of Lhx-6 and Lhx-7
genes.
 The restricted expression of goosecoid (Gsc) to establish expression in aboral
mesenchyme involves the repression by Lhx-6/Lhx-7 expressing cells.
 Although, the mechanism that restricts the oral mesenchyme is independent of
Gsc expression, the most probable factor that decides this would be the
distance from the source of Fgf-8.

90.  This opens up a cascade of molecular interactions that leads to the
establishment of oral–aboral axis and tooth development

91. Control of Tooth Germ Position
Fgf-8 has been proposed to act antagonistically with Bmp-4 to specify
the sites of tooth initiation and the former has been localized in the oral
ectoderm
 It is also shown that mesenchymal Bmp-2 and epithelial Bmp-4 antagonize the
induction of mesenchymal Pax-9 (paired box homeotic gene-9) by Fgf-8, a
member of Pax family, which helps to establish the position of prospective
tooth mesenchyme.
 Both Bmp-4 and Fgf-8 exhibit close interactions with each other

92. Bmp-4 and Fgf-8 are possibly regulated by transcription factors like
Prx-1 and Prx-2
 Another potential regulator of Fgf-8 is Pitx-2 whose epithelial
expression prefigures the location of teeth.
 Pitx-2 has been shown to be required for the progression beyond
epithelial thickening or bud stage.
 Thus Pitx-2 seems to regulate Fgf-8 in a positive feedback
mechanism while Bmp-4 in a negative feedback loops

93.  Lef-1 (Lymphoid enhancer factor) belongs to the family of T-cell factor
proteins.
 They are transcription factors that associate with beta catenin and
activate Wnt responsive target genes.
 Lef-1 is initially detected in the dental epithelial thickenings but later
during the bud stage shifts into the mesenchyme.
 Lef-1 is identified as a functional link that connects the intraepithelial Wnt
signal with epithelial to mesenchymal Fgf signaling.
 The requirement of Lef-1 in the dental epithelium earlier to bud formation
is to be considered since ectopic expression of Lef-1 in the oral
epithelium results in ectopic tooth formation.
Functional redundancy and their complexities

94. How the dentition is patterned
• In the mammalian dentition the teeth form a series of homologous structures whose
differences along the jaw axis can be described in terms of changes in shape and
size.
• Based upon the analysis of adult dentition, two classic theories have been proposed
to account for the developmental mechanisms responsible for patterning this axis.
THE FIELD THEORY
states that the
ectomesenchyme is only
programed to form teeth
of one family, but it is
acted upon by the local
factors which modify the
shape subsequently.
THE CLADE THEORY
or clone theory proposes
that the
ectomesenchyme is
initially programed into
different clones that form
the different families of
teeth.

95. The stream of neural crest cells that migrate into the first branchial arch is derived
from the neuroectoderm of the midbrain and the first two rhombomeres of the
hindbrain
Segment specific combinatorial
homeobox (Hox) gene expression
specifies the identity of each
rhombomere, thus the migrating
neural crest cells are expected to
carry their Hox code along with
them into the branchial arches.

96. A subfamily of the homeobox genes has been recognized within the first
branchial arch that shows spatial and temporal patterns of expression.
They include Msx genes and Dlx genes.
Msx-1, Msx-2 and Alx-3 are located in
the ectomesenchyme in horse shaped
fields in the anterior regions
(presumptive incisor region) of the first
arch.
Dlx-1, Dlx-2 and Barx-1 in the
proximal/posterior regions
(presumptive molar region) of the
arch.
Msx-1, Msx-2 and Dlx-2 are seen overlapping in the canine region.

97. Stomodeal thickening stage –
Dental lamina stage
.
Bmp-4 which appeared to inhibit tooth
development at early stages turns out to be
an inducer of molecules required for tooth
development at the stage of epithelial
thickening.
The genetic model thus proposed for the early tooth development consists of two
independent Msx-1 dependent pathways which are triggered by epithelial Fgf-8
and Bmp-4.

98. Stomodeal thickening stage – Dental
lamina stage
.
The cascade places Fgf-8 upstream of Msx-1 because of the presence of the
former in the epithelium.
Fgf-3 is placed downstream of Msx-1, since Fgf-3 expression is not observed in
Msx-1 mutant models and Bmp-4 is not able to induce its expression in the
mesenchyme

99. In situ hybridization experiments show that epithelial
Fgf-8 and mesenchymal Msx-1 and Bmp-4 expression is
preserved in Dlx double mutant upper molar
mesenchyme.
Conversely, in Msx-1 mutants, at the initiation stage, epithelial Fgf-3 and
mesenchymalDlx-1 and Dlx-2 expression are absent.
Also, Bmp-4 is not induced in the mesenchyme by Fgfs.
This shows that epithelial Bmp-4 can only induce Bmp-4 in the mesenchyme in
Msx-1 dependent manner.

100. Since Fgf-8 induces Fgf-3 in the mesenchyme at the transition of lamina–bud
stage which also coincides with the transfer of odontogenic potential from
epithelium to mesenchyme, Fgf’s may additionally be a component of signaling
cascade mediating epithelial mesenchymal interactions.
Moreover, Bmp-4 and Fgf-8 are able
to induce both Msx-1 and Dlx-2
expression in the dental mesenchyme
while Dlx-1 expression is induced by
Fgf-8. These results suggest that Msx
and Dlx might act parallel at the dental
lamina stage

101. Bud stage
At this stage, in contrast to what was proposed in
the lamina stage earlier,
 Dlx-2 is placed downstream of mesenchymal
Bmp-4 because of its reduced expression in
Msx-1 mutant.
 Bmp-4 could rescue the expression of Dlx-2
even in the absence of Msx-1.
 while Dlx-1 and Dlx-2 are likely to function in
parallel with Msx-1 and Msx-2 at lamina stage.
 Dlx-2 expression at the bud stage resides
downstream of Msx-1.
 This suggests the requirement of Bmp-4 and
Fgf-3 for the maintenance of Dlx-2 expression
and not for Dlx-1

102. Bud stage–cap stage
Msx-1 mutants arrest at the bud stage and Msx-2 mutants exhibit defects only at later
stages of tooth development.
Msx-1, Msx-2 double
homozygotes exhibit an arrest
at dental lamina stage which
affects all molar teeth.
Msx-1 mutant mesenchyme
shows reduced Bmp-4 and
addition of Bmp-4 rescues the
arrest at the bud stage.

103. Bud stage–cap stage
with Bmp-2 and Bmp-4
throughout bud and cap
along
remains
stage.
 Bmp-4 expression shifts to dental
mesenchyme.
 Msx-1 mutants show loss of
 mesenchymal Bmp-4, down regulation
of epithelial Bmp-2 and Shh
Bmp-4 is a component of inductive signal that induces the transfer of the tooth
inductive potential from dental epithelium to dental mesenchyme.
Also Bmp-4 is known to induce morphological changes in the dental mesenchyme
 Shh is expressed in the epithelium

104. Bud stage–cap stage
Blocking Shh expression with suitable antibodies also results in loss of Bmp-2. Thus
the effect of Bmp-4 on Bmp-2 is mediated by Shh.
The requirement of Shh in tooth development is time dependent.
Pax-9 is expressed in the bud stage mesenchyme and in the domains like that of
activin-bA and Msx-1 in patches of mesenchyme that marks the tooth formation
sites.
Thus these two genes are independently required for the progression of bud stage
in tooth development. However, changes do occur in other genes like Msx-1, Bmp-4
and Lef-1 in Pax-/- tooth bud mesenchyme

105. Tooth Morphogenesis
Morphogenesis is the process by which form is generated.
In the case of teeth, this can be considered the formation of crown and root shape.
The physical processes involve folding of dental epithelium, which begins from the
cap stage onwards
The first molecular signals involved in tooth morphogenesis are detected at the
bud stage and the bud to cap transition is a key checkpoint in tooth development.

106. Tooth Morphogenesis
Epithelial folding
appears to be
coordinated by the
enamel knots, with the
primary enamel knot
existing transiently as a
cylindrical rod of low
proliferating epithelial
cells that is clearly
visible at the cap stage.

107. Tooth Morphogenesis
Enamel knot consists of cells that do not divide but promote the division of adjacent
epithelial cells which form the cervical loop and the mesenchymal cells forming the
dental papilla.
Primary enamel knot cells express many
signaling factor proteins, including Shh,
Wnt, fibroblast growth factor (FGF), and
bone morphogenetic protein (BMP), which
coordinate the transition from bud to cap
and initiation of the epithelial folding
process.

108. Bmp-4 is a potent inducer of p21, a cyclin dependent kinase inhibitor
in the enamel knot.
Also another Bmp molecule, Bmp-2 expressed during this period in the dental
epithelium was able to induce enamel knot formation.
The expression of p21 correlates with withdrawal of cells from cell cycle
causing cessation of cell division.

109. Fgfs expressed in the enamel knot
can stimulate cell division in the
enamel epithelium and in the
dental papilla which is
demonstrated by the incorporation
of bromodeoxyuridine (Brdu).
The Fgf receptors are not present
in the enamel knot cells so they do
not respond to the mitogenic
stimuli.
Fgf-4 is the only stimulus that
strictly is restricted to the primary
and secondary enamel knots while
others rapidly spread into the
surroundings.
The Msx-2 is involved in regulating
Fgf-4 and/or genes responsible for
cessation of proliferation in enamel
knot.

110.  The cessation of cell proliferation in the enamel knot precedes the start of Fgf-
4 expression.
 Slit-1 is recently identified as another molecule apart from Fgf-4 that has been
localized in both primary and secondary enamel knot.
 Bmp-4 induces Lef-1, a transcription factor that conducts the epithelial–
mesenchymal interactions at a critical stage of tooth development when the
epithelium generates inductive signals to the mesenchyme for the formation of
the dental papilla.
 As the same signaling molecules are expressed by well studied vertebrate
signaling centers such as notochord, the apical ectodermal ridge and the zone
of polarizing activity, it was put forward that the enamel knot represents a
signaling center for tooth morphogenesis.

112. REFERENCES
1. Orban’s Oral histology and Embryology - 13th Edition G S Kumar (US Editor)
S N Bhaskar .
2. Ten cate's oral histology - 9th Edition Antonio Nanci
3. Fundamentals of oral histology and physiology - R. Hand, marion E. Frank
4. Textbook of dental and oral histology with embryology - satish chandra, shaleen
chandra, mithilesh chandra, mithilesh chandra, nidhee chandra.
5. Essentials of oral histology and embryology - james k. AVERY, danielj. Chiego