This document summarizes key aspects of tooth development, structure, and genetic conditions. It discusses the embryology and signaling pathways involved in tooth formation such as SHH, BMP, WNT, and FGF. Mutations in these pathways can result in dental anomalies like tooth agenesis, fusion, or altered morphology. The structure and differences between primary and secondary dentition are outlined. Genetic conditions associated with changes in signaling include FOP (ACVR1), SSPS and OODD (WNT10A), and taurodontism. The chronology and factors influencing tooth eruption are also summarized.

1. Dr Ebin Roshan Paul
Assistant Professor & Clinical Geneticist
PKDAS IMS Ottapalam Kerala

2.  Structure of tooth
 Embryology
 Signalling pathways
 Genetic conditions with abnormal signalling
 Primary and Secondary dentitions

3. Introduction
 Hardest substance of body (enamel), epithelial appendages
 Human
Heterodont : 4 types of teeth
Diphyodont : 2 successive set of teeth
Thecodont : enclosed teeth in jaw cavity
Monophyodont, polyphyodont, homodont/ isodont

4. Structure of tooth
Crown : enamel
Root: cementum
Neck: cervical line
Cervical constriction

6.  Stages of development: oral epithelium  Dental Lamina 
Dental Placode  Dental Bud  Dental Cap  Bell Stage
~6 weeks ~ 8 weeks ~ 10 weeks ~ 3 month

9.  Cusp: occlusal or incisal eminence on tooth surface,
determined by “enamel knot”

10. Enamel Knot
 “signalling center”/ organiser for early development
 Cluster of IDE seen at tip of dental bud / apex of dental cap
 Regulate shape of tooth and location of cusp.
 Apoptosis and disappear.
 1 enamel knot = 1 cusp
SHH
BMP 2/4
FGF4

11.  Premolar/ Molar : multiple cusp  multiple enamel knot
 2◦ enamel knot formed from primary
 2 molecules from BMP determine its spacing and location
P21 ectodin
at site of knot intervening space

13.  Lengthening of root push crown to oral cavity by 6-13
month, first lower central incisors.
 Buds for permanent teeth form by 3 month  remain
dormant 6 years PN life  begins to grow, push and shed
milk teeth located above.
Oral epithelium Mesenchyme
Ameloblast cells Odontoblast cells
Dental enamel Dentin
Crown Crown and Root

15. Talon cusp (dens evaginatus)
 Anomaly seen inner surface of anterior tooth
 1-6% population
 Highly specific for RTS and OFDS II
 “eagle talon”

17. Cusp of Carabelli
 Small additional cusp in Max 1st M
 Initially proposed
 Polygenic trait
Homozygous : tubercle
Heterozygous : pit / groove / bulge
(kraus 1951)

18. Mamelons
French “nipple”
One of the three projection seen in IE of incisors
Wear off in early life
Preserved in anterior open bite
Not seen in 1◦ dentition

19. Primary and Secondary dentition
 Diphyodont, Heterodont, Thecodont
 1 ◦ : 20 number
 2◦ : 32 number
Dentition In Can preM M
1◦ 2 0 2 1
2◦ 2 1 2 3

20. Comparison 1◦ and 2◦ dentition
1◦ dentition 2◦ dentition
Size small , light colour Large size, darker colour
Narrow cervical constriction Broad cervical constriction
No mamelon 3 mamelons seen
Canines: conical & pointed Less conical & pointed
Enamel and dentin thin Thick
More caries prone Less
Neonatal lines seen in all teeth Only in first molar tooth

21. Neonatal line
 Bands of incremental growth line seen in histology
 Forensic dentistry timing of birth and hours lived
 All primary and 1st Molar
 Antenatal enamel calcified better than post natal

22. Chronology of dentition
 Depend on growth and nutrition status
 Delayed dentition: 13 month (mean + 3SD)
 Causes: HypoT, HypoParaT, familial, idiopathic,
mechanical cause (crowding, gum fibrosis).
Mineralisation
Eruption
Shedding

24. Evolution and Dentition
25 million 5 million 3 million

25. Taurodontism
Atavistic
KFS
FDH
X aneuploidy

27. Signalling pathways
 ~ 10 different signalling identified at various stages.
 Wnt
 BMP
 FGFs
 SHH
 TNF
 TF  msx1 and msx2

28. Sonic Hedgehog (SHH)
 Early 90’s : “Sonic the Hedgehog” game
 Sonic: had two closely set eyes with a common scleral rim.
 Holoprosencephaly seen in SHH knock out mice. (SHH-/-)

29.  Major signalling in  embryonic morphogenesis
 patterning of limbs and digits
 CNS formation and patterning
 cancers of breast, skin, CNS, liver
Dental development at multiple stages

30. Altered signals clinical features
 ↓/ loss of signal  molar fusion, tooth rudiments, poor dental
lamina invagination, altered polarity of enamel and dentin.
 ↑ signals  supernumerary tooth
 SHH is not needed for ameloblast and odontoblast
differentiation so amount will be same but polarity and
organisation are severe distorted.

32. BMP signalling
 Name ? Induce osteogenesis and repair in demineralised
bone extract ‘invitro’
 ~20 proteins in Superfamily of TGFβ
 BMP 2/4 mainly, recently BMP 7

33. BMP & Dental development
 Functions  “bud to cap” stage ( epithelio-mesenchymal
interactions)
 formation, regulation, apoptosis of “enamel knot”
 differentiation of ameloblast from IDE
 spacing between teeth, 2◦ molar cusp formation

34. Dental spacing and 2◦ molar cusp
 BMP inhibit FGF8 and also via lateral inhibition via
delta/notch system for spacing.
 BMP induce ectodin and p21 to determine 2◦ molar cusp.
p21 expressed in cusp and ectodin in intervening spaces.

35. Lack BMP signalling
 Lack of cusp and ameloblast differentiation
 Tooth arrest at lamina/early bud stage
 Lack of “ectodin” massive molar cusp

36. Genetic condition
 BMP4 (ACVR1 gene) “turn on” Type 1 receptor  FOP

37. WNT signalling
 Highly evolutionary conserved signal transduction pathway.
 WNT
 3 ways signalling: canonical/noncanonical /calcium
 Tooth
Oral epithelium  Wnt 3/4/6/7b/10a/10b
Mesenchyme Wnt 5a
Wingless  wingless drosophila
Int-1 (Integration 1)

38. Mutations in Wnt & Dental
 Wnt 10a : ectodermal dysplasia syndromes, odonto-
onchyo-dermal dysplasia (OODS), schopf-schulz-passarge
syndrome (SSPS), AD isolated hypodontia.
 Axin 2: oligo/hypo dontia
 LRP6: NS AD oligodontia

39. Schopf Schulz Passarge Syndrome
(SSPS)
 AR
 WNT10a gene (2q35)
 Ectodermal dysplasia
 Allelic to OODS

40.  Palmoplantar keratoderma
 Hypo/oligo dontia
 Hypotrichosis
 Nail dystrophy
 Apocrine hidrocystomas
 Smooth red tongue

41. Odonto- Onycho -Dermal-Dysplasia
(OODD)
 AR trait
 Wnt 10a gene (2q35)
 Allelic to SSPS, so similar CF
 No apocrine hidrocystomas

43. Reference
 Wheeler’s Dental anatomy 9th edition
 Langmans medical embryology 12th edition
 Genetic basis of dental agenesis: A systematic review Med Oral Patol Oral
Cir Bucal. 2014 Mar 1;19 (2):e112-9.
 Molecular Genetics of Tooth Development Curr Opin Genet Dev. 2009
October ; 19(5): 504–510.
 Tooth eruption disorders associated with systemic and genetic diseases: J
Dentofacial Anom Orthod 2017;20:402
 The genetic basis of inherited anomalies of the teeth: European Journal of
Medical Genetics 51 (2008) 273e291
 Genetic Basis of Supernumerary Tooth J. of Biomed. &Clin. Sci. June 2019
Vol 4 (1), 26-33