Clinical consideration in odontogenesis

1. Clinical Consideration in Tooth Development
PRESENTED BY : Dr. SHASHI BHAL MAURYA
MDS FIRST YEAR
ORAL AND MAXILLOFACIAL
PATHOLOGY AND MICROBIOLOGY

2. INTRODUCTION
• Teeth are specialized structural components of the craniofacial skeleton and are comprised of : enamel, dentin, and
cementum.
• Developmental defects occur in each of these mineralized tissues, either alone (isolated), or in a combination
(syndromic) with defects in other organs or tissues

3.  Four signalling pathways, are repeatedly used throughout tooth development.
 the bone morphogenetic proteins (Bmp),
 fibroblast growth factors (Fgf),
 sonic hedgehog (Shh),
 wingless-related (Wnt) pathways
 Inactivation of any of these resulted in early tooth developmental arrest in mice.

4. E 11.5 – thickening of oral epithelium
Expression of key signaling molecules
Bmp, Fgf, Wnt, Shh
Blocking each of these molecules results in tooth
arrest in dental lamina or bud stage
Bmp and Fgf signaling is required for activation
of expression of the Msx1 and Pax9

6. COMPLETE
ANODONTIA
PARTIAL
ANODONTIA

7. Kazhila C. Chinsembu ,Teeth are bones: Signature genes and molecules that underwrite odontogenesis
Journal of Medical Genetics and Genomics Vol. 4(2),March 2012
Wnt signaling is required early in tooth germ formation and interference
with signaling via addition of an antagonist results in retarded
development and formation of smaller teeth; mutation of β-catenin
causes formation of large, misshapen teeth buds and ectopic teeth.

8. E 11.5 – thickening of oral epithelium
Epithelium proliferates and invaginates into
the neural crest cell derived mesenchyme
and forms BUD
E 13.5 – BUD clearly forms and surrounded
by the condensing mesenchyme
Prior to the transition of bud to cap primary enamel
knot forms at the tip of the tooth bud.
And exihibits restricted expression of Bmp, Fgf, Wnt

9. ENAMEL KNOT
 Bmp4 signaling from condensing mesenchyme and p21 from dental epithelium– induction of enamel
knot.
 Plays central role in patterning of tooth crown by regulating growth and folding of the epithelium.
Addition of Bmp4 in oral epithelium
Upregulation of enamel knot marker such as p21
Overexpression of P21 –enlarged enamel knot and cuspal defects.
Like Dense in Dente, Dense Evaginatus, Talons cusp

10. DENSE IN DENTE DENSE EVAGINATUS TALON CUSP

11. E 14.5 - high proliferation outside the enamel knot
and low proliferation within the knot
Forming cap shape structure
If the shape of enamel knot is too small with mutation
of Eda or Edaradd (Eda expression is regulated by Wnt)
Hypohidrotic Ectodermal Dysplasia
Characterized by presence of molars with reduced
cusps and peg like teeth.
If Wnt signaling blocked in early bell stage when the secondary enamel knot is forming
--- again expression of Eda will reduced and molar forms with flattened cusps

12. Reducing tooth number
• It can be due to—
FUSION-fusion of existing tooth germ to form single compound tooth.
Fusion observed in-
 SMMCI (single median maxillary central incisor syndrome)
 Caused by failure in growth in midline, stimulated by a defect in SHH
signalling pathway (Nanni et al 2001)

13. Increase in tooth number
 In the wild-type mouse mandible,
• one incisor forms from each incisor placode,
• three molars (M1, M2 and M3)forming from the molar placode.
1. One way increase number of tooth is to increase the number of placode.
(Ectopic application of Shh has been shown to lead to formation of ectopic tooth germs).
2. SPLITTING OF TOOTH GERM (GEMINATION): Rabbit molars were halved two miniature molars formed
(Glasstone 1952)
3. Multiple teeth have been shown to arise from the molar field in mice where β-catenin has been overexpressed (Jarvinen et al.
2006; Liu et al. 2008).
a) In mice - a) molar region was explanted in to kidney capsule three molars forms.
b) Molar region explanted into β-catenin mouse 40 teeth forms (Jarvinen et al.2006).
 The initial tooth buds form normally, but the dental epithelium then starts to undergo further budding and
invaginations, leading to the formation of additional enamel knots and additional teeth and leads to the formation
of ODONTOMA.
4. Similar overproduction has been described in Epfn mutant mouse (Nakamura et al. 2008).
5. In human patients with a mutation in APC (is a Wnt modifier) supernumerary teeth and odontomas are observed (Fader
et al. 1962; Wolf et al. 1986; Wang et al. 1998)

14. Changing the complexity
 Complexity of tooth- Altered by addition or removal of tooth.
 Etiology -
1) Diet- diet dependent changes of dental pattern seen in both carnivores and rodents (Evans et al
2007)
2) Formation of additional enamel knot- overstimulation of Eda signaling pathway
3) NUMBER of cusp depends on both cusp size and tooth size.
• Larger tooth –more space to develop additional cusp
• If cusp is smaller – more cusp can be be fitted in (Cai et al 2007)
• Eg. Small molar (artificially created ) by recombining a small number of
mesenchymal cells with tooth epithelium number of cusp generated
was reduced(Hu et al 2006)

15. Mineralization:epithelial mesenchymal interaction
 After the disappearance of the secondary enamel knot signalling centres, cells
of the tooth organ terminally differentiates-
•Inner enamel epithelium cells – Ameloblastoma
•Dental pulp mesenchyme- Odontoblast
Tgfb1, Fgfs, and Bmp2
Induce polarization of Odontoblast
(Begue-et al 1994)

16. The later stages of tooth development are characterized by the formation of the mineralized tissue:
dentin,cementum and enamel. Dentin and cementum have significant similarities with bone.
(Linde & Goldberg, 1993),
 ENAMEL:
 Inherited enamel defect known as Amelogenesis imperfecta.
 Ameloblast secretes two major class of proteins-
 Nonglycosylated –amelogennin – 90%of enamel matrix
 Glycosylated – Tuftelin
• Ameloblastin
• Enamelin
 Enamelin (ENAM) – main candidate responsible for autosomal inherited form of Amelogenesis
Imperfecta.
 Amelogenin (AMLEX) mutation leads to X-linked Amelogenesis Imperfecta.
 Also occurs due to mutation in Enamelysin and Kallikrein (KLK4).

17. DENTIN
 Dentinal defects are classified into
 dentin dysplasia type 1 and type 2
 dentinogenesis imperfecta type 1,
 type 2 and type 3
 Dentinogenesis imperfecta universally designated as Osteogenesis imperfecta
with Dentinogenesis imperfecta.
 Occurs due to mutation in type1 collagen.
 Dentin dysplasia type 1 and type 2
 Dentinogenesis imperfecta
 Mutation in DSPP, COL1A1 AND
COL1A2

18. Root formation

19. Expression of Bone Morphogenetic Proteins and Msx
Genes during Root Formation
Journal of Dental Research, Mar2003, Vol. 82 Issue 3, p172-176, 5p, 3 Color Photographs, 1 Chart
Color Photograph; found on p174

20.  trauma to the calcified portion of the tooth germ which alters the
angulation of the tooth during root formation leads to .Dilaceration
.(NEVILLE)

21.  The formation of ectopic enamel requires the presence of differentiated ameloblasts apical to the CEJ.
In humans, Hertwig's epithelial root sheath (HERS) or its residues, the epithelial rests of Malassez have
been implicated as the likely sources of ectopic ameloblasts.
Shivani sharma et al Enamel pearl on an unusual location associated with localized periodontal disease: A clinical report, J
Indian Soc Periodontol. 2013 Nov-Dec; 17(6): 796–800
If cells of the epithelial root sheath remain adherent to the dentin surface, they may differentiate into
fully functioning ameloblasts and produce enamel. Such droplets of enamel called Enamel pearls,
Mass of ectopic enamel located in
the furcation area of a molar tooth.

22. Genetic defects occurring late in tooth development
 DLX3 mutation causes the deformation in multirooted tooth known as TAURODONTISM
(Bull like shape).
 HYPOPHOSPHATASIA is a bone disorder caused by mutation in ALPL (alkaline
phosphatase).
 Histological examination of pt with hypophophatasia
 Shows lack of both cellular and acellular cementum formation.

23. References…
 NEVILLE, ALLEN, BOUQUOT Oral and Maxillofacial Pathology third edition
 Shafer’s text book of oral and maxillofacial pathology seventh edition
 Orban’s oral histology and embryology 13th edition.
 Aswathy Raj,Deepa.M.S, Ahmed Hasan Farooqi GENETICS AND TOOTH ANOMALIES - AN
UPDATEOral & Maxillofacial Pathology Journal Vol. 4 No. 1 Jan - June 2013
 Hattab FN, Yassin OM, Al-Nimri KS. Talon cusp in the permanent dentition associated with
other dental anomalies: Review of literature and reports of seven cases. J Dent Child
1996;63:368-76.
 Danker E, Harari D, Rotstein I. Dens evaginatus of anterior teeth. Literature review and
radiographic survey of 15,000 teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
1996;81:472-76
 Thaleia Kouskoura1 Natassa Fragou1 Maria Alexiou1 Nessy John2 Lukas Sommer2,The genetic
basis of craniofacial and dental abnormalities, Schweiz Monatsschr Zahnmed Vol. 121 7/8/2011

24.  Johannes G Dauwerse1, Mutations in genes encoding subunits of RNA polymerases I and III
cause Treacher Collins syndrome, NATURE GENETICS, VOLUME 43 | NUMBER 1 |
JANUARY 2011 .
 Current knowledge of tooth development: patterning and mineralization of the murine
dentition Javier Catón and Abigail S. Tucker Department of Craniofacial Development and
Orthodontics, King’s College London, Floor 27, Guy’s Tower, Guy’s Hospital,London, UKJ.
Anat.(2009)214 pp502–515.
 Teeth are bones: Signature genes and molecules that underwrite odontogenesis Kazhila C.
Chinsembu Journal of Medical Genetics and Genomics Vol. 4(2), pp. 13 - 24, March 2012
 Jan C-C. Hu, James P.,Developmental biology and genetics of dental malformations Orthod
Craniofacial Res 10, 2007; 45–52

25. THANKYOU