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Craniofacial and Tooth Biology > 13. Genetics of Tooth Development > Flashcards

13. Genetics of Tooth Development Flashcards

1
Q

Explain the statement ‘combinatorial cell signalling induces genetic programmes’

A
  • 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
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2
Q

Key list of signalling molecules

A
  • Wnt6
  • Fgf8
  • Tgf-beta3
  • Bmp4
  • Shh
  • Eda
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3
Q

Key list of transcription factors

A
  • Hoxa2
  • Msx1
  • Dlz1/2
  • Barx1
  • Pax9
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4
Q

How to define the odontogenic potential

A
  • 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
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5
Q

The odontological potential switches from … to …

A
  • epithelium (in initiation)
  • mesenchyme (bud stage)
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6
Q

2 combinations of odontological potential which results in tooth formation

A
  • dental epithelium (11.5)+ non-dental mesnchyme (11.5)
  • non-dental epithelium (13.5) and dental mesenchyme (13.5)
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7
Q

Signalling in the initiation phase

A
  • 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
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8
Q

Signalling in bud stage

A
  • dental mesenchyme secretes signalling molecules (FGF, BMP)
  • induces formation of enamel knot (non-dividing cells) in dental epithelium
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9
Q

Signalling in cap stage

A
  • 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
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10
Q

Tooth development proceeds through … stages
Genetic modules …
Mutations …

A
  • 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
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11
Q

What can arrest tooth development at early stages?

A

mutations in key genetic regulators

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12
Q

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

A
  • lamina
  • variable expression levels
  • to early signalling centre
  • division of domains
  • to primary enamel knot
  • further subdivision
  • to secondary enamel knots
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13
Q

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

A

odontogenic homeobox code

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14
Q

Defects during tooth initiation affect …

A
  • tooth number and identity
  • e.g ectodermal dysplasia, hyperdontia
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15
Q

Defects during tooth morphogenesis affect …

A
  • tooth number, shape and size
  • e.g hypodontia, hyperdontia
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16
Q

Defects during tooth histogenesis affect …

A
  • hard tissue formation
  • e.g amelogenesis imperfecta, dentinogenesis imperfecta
17
Q

What other things can cause dental anomalies? Examples?

A
  • various cellular defects e.g eruption, replacement, tumours
  • e.g osteopetrosis, eruption cysts, odontomes
18
Q

Early defects in development cause what kind of issues?

A
  • missing teeth
  • supernumerary teeth
  • abnormalities of tooth shape and size
19
Q

Late defects in cell differentiation cause what kind of issues?

A
  • anomalies in structure of teeth like dentine and enamel
  • anomalies in tooth eruption or resorption
20
Q

2 classifications of dental defects

A
  • syndromic
  • non-syndromic
21
Q

Define ‘syndromic dental defects’

A
  • dental defects shown in combination with other anomalies
22
Q

Define ‘non-syndromic dental defects’

A
  • dental defects are not associated with any other anomalies
23
Q

Define ‘hypodontia’

A
  • less than 6 missing teeth exc. 3rd molars
24
Q

Define ‘oligodontia’

A
  • more than 6 missing teeth exc. 3rd molarsef
25
Q

Define ‘anodontia’

A

no teeth

26
Q

Define ‘hypohidrotic ectodermal dysplasia’

A
  • severe oligodontia
  • conical tooth shape
27
Q

Define ‘Rieger syndrome’

A
  • missing maxillary incisors and molars
28
Q

Define ‘oligodontia-colorectal cancer syndrome’

A
  • severe oligodontia
  • affects molars, premolars, lower incisors, upper lateral incisors
29
Q

Characteristics patterns of missing teeth caused by MSX1 mutations

A
  • 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
30
Q

Characteristics patterns of missing teeth in PAX9 mutations

A
  • 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
31
Q

Clinical management of hypodontia

A
  • 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
32
Q

Explain hyperdontia
- cleidocranial dysplasia
- duplication of dental lamina

A
  • 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
33
Q

Explain tooth malformations in bell stage when dental lamina breaks down

A
  • incomplete removal of epithelial remnants can lead to …
  • supernumerary teeth (reactivation of tooth development programme)
  • eruption cysts (delayed eruption)
  • odontomes (tumours)
34
Q

Explain ‘amelogenesis imperfecta’

A
  • 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
35
Q

Explain dentinogenesis imperfecta

A
  • 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)

Craniofacial and Tooth Biology (25 decks)

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