13. Genetics of Tooth Development

Question 1

Explain the statement ‘combinatorial cell signalling induces genetic programmes’

Answer 1

• combination of transcription factors within given cell regulates expression of signalling molecules among other proteins
• different signalling molecules are secreted and bind to corresponding receptors on surface of surrounding cells
• signals from different receptors are integrated along pathways within receiving cells and result in activation of other transcription factors that establish different genetic programmes

Question 2

Key list of signalling molecules

Answer 2

• Wnt6
• Fgf8
• Tgf-beta3
• Bmp4
• Shh
• Eda

Question 3

Key list of transcription factors

Answer 3

• Hoxa2
• Msx1
• Dlz1/2
• Barx1
• Pax9

Question 4

How to define the odontogenic potential

Answer 4

• by experiment
• dissection of mandibular arch
• enzymatic digestion to isolate epithelium and mesenchyme
• recombination of epithelium and mesnchyme followed by short period of in vitro culture
• transplantation of tooth germ into kidney capsule and in vivo culture for 2-3 weeks
• tissue analysis

Question 5

The odontological potential switches from … to …

Answer 5

• epithelium (in initiation)
• mesenchyme (bud stage)

Question 6

2 combinations of odontological potential which results in tooth formation

Answer 6

• dental epithelium (11.5)+ non-dental mesnchyme (11.5)
• non-dental epithelium (13.5) and dental mesenchyme (13.5)

Question 7

Signalling in the initiation phase

Answer 7

• overlapping gradients of signalling molecules (morphogens and FGF, BMP) in dental epithelium
• these induce transcriptional response (PAX9, MSX1) in dental mesenchyme
• determination of tooth position

Question 8

Signalling in bud stage

Answer 8

• dental mesenchyme secretes signalling molecules (FGF, BMP)
• induces formation of enamel knot (non-dividing cells) in dental epithelium

Question 9

Signalling in cap stage

Answer 9

• enamel knot secretes signalling molecules that induce cell cycle arrest (BMP) within enamel knot cells
• induces cell proliferation (FGF) in surrounding cells
• determination of tooth shape

Question 10

Tooth development proceeds through … stages
Genetic modules …
Mutations …

Answer 10

• characteristic morphological
• are reused to regulate subsequent developmental stages
• in key genetic regulators arrest tooth development at early stages e.g PAX9 and MSX1, ectodermal dysplasia causing hypodontia

Question 11

What can arrest tooth development at early stages?

Answer 11

mutations in key genetic regulators

Question 12

Use Shh expression in dental epithelium and enamel knot for repeated use of signalling molecules

Answer 12

• lamina
• variable expression levels
• to early signalling centre
• division of domains
• to primary enamel knot
• further subdivision
• to secondary enamel knots

Question 13

How do you show the hypothesis for specification of tooth identity?

Answer 13

odontogenic homeobox code

Question 14

Defects during tooth initiation affect …

Answer 14

• tooth number and identity
• e.g ectodermal dysplasia, hyperdontia

Question 15

Defects during tooth morphogenesis affect …

Answer 15

• tooth number, shape and size
• e.g hypodontia, hyperdontia

Question 16

Defects during tooth histogenesis affect …

Answer 16

• hard tissue formation
• e.g amelogenesis imperfecta, dentinogenesis imperfecta

Question 17

What other things can cause dental anomalies? Examples?

Answer 17

• various cellular defects e.g eruption, replacement, tumours
• e.g osteopetrosis, eruption cysts, odontomes

Question 18

Early defects in development cause what kind of issues?

Answer 18

• missing teeth
• supernumerary teeth
• abnormalities of tooth shape and size

Question 19

Late defects in cell differentiation cause what kind of issues?

Answer 19

• anomalies in structure of teeth like dentine and enamel
• anomalies in tooth eruption or resorption

Question 20

2 classifications of dental defects

Answer 20

• syndromic
• non-syndromic

Question 21

Define ‘syndromic dental defects’

Answer 21

• dental defects shown in combination with other anomalies

Question 22

Define ‘non-syndromic dental defects’

Answer 22

• dental defects are not associated with any other anomalies

Question 23

Define ‘hypodontia’

Answer 23

• less than 6 missing teeth exc. 3rd molars

Question 24

Define ‘oligodontia’

Answer 24

• more than 6 missing teeth exc. 3rd molarsef

Question 25

Define 'anodontia'

Answer 25

no teeth

Question 26

Define 'hypohidrotic ectodermal dysplasia'

Answer 26

- severe oligodontia - conical tooth shape

Question 27

Define 'Rieger syndrome'

Answer 27

- missing maxillary incisors and molars

Question 28

Define 'oligodontia-colorectal cancer syndrome'

Answer 28

- severe oligodontia - affects molars, premolars, lower incisors, upper lateral incisors

Question 29

Characteristics patterns of missing teeth caused by MSX1 mutations

Answer 29

- high frequency of agenesis in 3rd molars and 2nd premolars - medium frequency in lower incisors, lateral uppers, 1st premolars, 1st molars, 2nd lower molars - low frequency is upper central incisors, canines, lower 1st premolars, upper 2nd molars

Question 30

Characteristics patterns of missing teeth in PAX9 mutations

Answer 30

- high frequency of agenesis of 2nd and 3rd molars - medium in lower central incisors, upper laterals, 2nd premolars, 1st molars - low in upper centrals, lower laterals, canines, lower 1st premolars

Question 31

Clinical management of hypodontia

Answer 31

- a multidisciplinary team approach with orthodontist, child dental health dentist, restorative dentist, maxillofacial surgeon, psychologist, geneticist - treatment options are open spaces for bridges or implants, close spaces using orthodontic devices

Question 32

Explain hyperdontia - cleidocranial dysplasia - duplication of dental lamina

Answer 32

- gene mutation RUNX2 (autosomal dominant) - bone defects in clavicle and craniofacial malformations - multiple teeth (upper incisors, lower premolars), enamel hypoplasia - delayed eruption (causes impacted teeth) and malocclusion - dentigerous cysts (radiolucency caused by fluid-filled space between REE and tooth crown) - duplication of dental lamina can cause multiple tooth rows

Question 33

Explain tooth malformations in bell stage when dental lamina breaks down

Answer 33

- incomplete removal of epithelial remnants can lead to ... - supernumerary teeth (reactivation of tooth development programme) - eruption cysts (delayed eruption) - odontomes (tumours)

Question 34

Explain 'amelogenesis imperfecta'

Answer 34

- defects in enamel formation/ameloblasts - hypoplasia (affects enamel matrix formation - reduced enamel thickness) - hypomineralisation (normal enamel thickness but decreased mineral content) - hypomaturation (normal enamel thickness but mottled and softer/chipped teeth) - prevalence 1 in 4000 to 15,000 - inheritance - AD, AR, X-linked forms - gene mutations in AMELX, ENAM, MMP20, KLK4

Question 35

Explain dentinogenesis imperfecta

Answer 35

- defects in dentine formation/odontoblasts - blue-gray or amber, brown opalescent teeth - soft dentine, enamel chipping, teeth wear down rapidly - bulbous crowns and short narrow roots - obliterated pulp chambers - prevalence 1 in 6000 to 8000 - inheritance - AD - gene mutation - DSPP (DSP, DGP, DPP)