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May14 Oral Histology > EX1; Molecular and Genetic Basis of Tooth Development > Flashcards

EX1; Molecular and Genetic Basis of Tooth Development Flashcards

1
Q

Where are cranial neural crest (NCC) cells formed

A

at the back of the neural tube and begin to migrate when the neural tube closes

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2
Q

Where do NCC cells migrate to

A

branchial arches

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3
Q

What specifically are NCC cells

A

stem cells

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4
Q

When do the branchial arches form

A

week 4

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5
Q

In which branchial arch are teeth derived from

A

arch 1

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6
Q

What can stem cells replicate to become

A

copies of itself or differentiate into other cell types

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7
Q

What are the two divisions of stem cells

A

symmertric (same)

asymmetric (different)

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8
Q

What cells concerning tooth development are differentiated from NCCs

A

odontoblasts

cementoblasts

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9
Q

Structure development, including odontogenesis at the right location and time, is through what

A

tissue-tissue interaction

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10
Q

This tissue-tissue interaction regulates NCC cells during morphogenesis and controls the position, size, and shape of organs

A

ectoderm - NCC

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11
Q

This tissue-tissue interaction provides environment for NCC cells to populate

A

mesoderm - NCC

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12
Q

This tissue-tissue interaction developed pharyngeal pouch generated organs; thyroid, parathyroids, and thymus

A

endoderm - NCC

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13
Q

NCCs form well-organized what

A

migratory streams to the branchial arches

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14
Q

NCCs for the first branchial arch are formed from which hindbrain rhmobomeres

A

1 and 2

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15
Q

Hindbrain-derived neural crest cells migrate into what three streams

A

first branchial arch; 1 and 2
second branchial arch; 4
third branchial arch; 6 and 7

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16
Q

The branchiomotor nerves collect axons from cell bodies but exit the hindbrain only from what to innervate their peripheral target structures

A

the even numbered segments

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17
Q

What cranial nerve is associated with r1-3; 1st branchial arch structures including teeth

A

trigeminal (V)

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18
Q

What cranial nerve is associated with r4-5

A

facial (VII)

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19
Q

What cranial nerve is associated with r6-7

A

glossopharyngeal (IX)

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20
Q

NCCs in each migratory stream express specific what

A

Hox gene codes

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21
Q

This is a group of homeobox genes, which possess a unique homeobox (DNA sequence) which encodes a conservative homeodomain (protein segment)

A

Hox genes

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22
Q

If a Hox gene is expressed, its protein products functions as what

A

a transcription factor; controling gene expression

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23
Q

True or False

In specific NCC streams, there is a specific Hox gene profile

A

True

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24
Q

What becomes of r3 and r5

A

they undergo apoptosis

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25
Q

What is unique about the NCCs that migrate to the first branchial arch regarding the Hox genes

A

the first branchial arch is Hox free; it carries the genes, but does not express them

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26
Q

NCCs involved in tooth development do or do not express Hox genes

A

DO NOT

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27
Q

Within each branchial arch, these genes are expressed to produce regional differences, such as between the maxillae and mandible

A

specific D1x gene codes

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28
Q

True or False

D1x genes are not homeobox

A

False; they are

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29
Q

True or False

D1x genes are not transcription factors

A

False; they are

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30
Q

How many members compose the D1x family

A

7

7, 8, 9 are actually the same gene

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31
Q

For branchial arch 1, D1x 1/2 combination is required for what

A

development of the proximal portion (maxillary process)

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32
Q

What do D1x 1/2 mutants lack

A

all maxillary molars;

mandibular structures are not affected

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33
Q

For branchial arch 1, D1x 5/6 combination is required for what

A

development of the distal portion (mandibular process)

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34
Q

What do Dx1 5/6 mutants look like

A

the lower jaw looks like a mirror image of the upper jaw

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35
Q

Normal tooth development is a process with precisely arranged/regulated what

A

cell and tissue interactions

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36
Q

The interaction between the epithelium and the mesenchyme is through what

A

numerous molecules

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37
Q

What is the entire process of tooth development initiated by

A

epithelium followed by epithelium-mesencyhme interaction

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38
Q

What are the four major signaling pathways for the ectoderm-derived epithelium

A

BMP; bone morphogenic protein
FGF; fibroblast growth factor
Wnt; wingless (drosophila) and int (mouse)
SHH; sonic hedgehog

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39
Q

The four major singling pathways bind to what

A

cell membrane receptors

40
Q

The four major signaling pathways eventually impact on gene regulation through what

A

varied intracellular pathways

41
Q

The four major signaling pathways are also important for the development of what

A

other ectodermal organs such as hair, nails, and glands

42
Q

These are epithelial aggregates that function as signal centers for tooth morphogenesis and odontoblast differentiation

A

enamel knots

43
Q

Which enamel knot appears at the end of the bud stage and which one appears at the locations of future molar cusps at the bell stage

A

primary EK

secondary EK

44
Q

Which enamel knot closely interacts with the mesenchyme

A

primary EK

45
Q

Which enamel knot stimulates terminal differentiation of odontoblasts at the end of the bud stage, which always occurs first at the location of future cusps/cusps tips

A

secondary EK

46
Q

Which enamel knot strongly stimulates proliferation of adjacent cells

A

primary EK

47
Q

Which enamel knot is essential for bud to cap transition and without it, tooth development will be arrested

A

primary EK

48
Q

Which enamel knot determines the number of cusps and locations of the molar cusps

A

secondary EK

49
Q

Which enamel know disappears by cell apoptosis

A

primary EK

50
Q

Which enamel knot is not present in incisors

A

secondary EK

51
Q

This signaling molecule signaling molecule as a cusp activator

52
Q

This signaling molecule functions as a cusp inhibitor

A

BMP (and possibly SHH)

53
Q

What do FGF and BMP (and possibly SHH) regulate in terms of the cusps

A

the formation of inter-cusp distance

54
Q

All tooth structures except for what are directly contributed by NCCs migrated to the first branchial arch

A

enamel

dentin, pulp, periodontal ligament, and cementum

55
Q

What are the important signaling molecules produced by the mesenchymal cells for tooth development

A

BMP, FGF, Wnt, and their inhibitors

56
Q

What are the important transcription factors produced by the mesenchymal cells for tooth development

A

Ms x1/2, D1x 1/2, Pax9, Gli 2/3, Runx2, Barx1, etc.

57
Q

At the cell and molecular level, the development of a tooth crown can be divided into what three major stages

A
  1. initiation
  2. morphogenesis
  3. differentiation and mineralization
58
Q

What occurs through all of the tooth crown development stages

A

intense molecular interaction

59
Q

Which signaling molecules are present at the anterior sites which control the development of incisors

A

BMP4 Msx1, Msx2

60
Q

Which signaling molecules are present at the posterior sites which control the development of molars

A

FGF Barx1, D1x2, Lhx6/7

61
Q

Innervation of the tooth is from beaches of which cranial nerve

A

trigeminal

62
Q

When do pioneer trigeminal axons penetrate into the dental pulp after what

A

the start of enamel formation

63
Q

Through the epithelial-mesenchymal interation, the epithelium expresses what into mesenchyme

64
Q

Sema3A serves as what

A

chemorepellent for the axons, thus controlling the timing and patterning of tooth innervation

65
Q

After the crown development is nearly complete, this grows apically between two mesenchymal regions; dental papilla and dental follicle

A

Hertwig’s root sheath (HERS)

66
Q

Immediately after HERS formation, these appear adjacent to the HERS on the papilla side

A

apical odontoblasts

67
Q

This is required for root development

A

induction from the enamel epithelium

68
Q

HERS induces dental papilla cells to do what

A

differentiate into odontoblasts

69
Q

Recent evidence shows that this may be secreted by HERS to induce odontoblast differentiation

A

lamini-5 and transforming growth factor-beta (TGF-β)

70
Q

What is different about the odontoblasts in the root region compared to the crown region

A

they are much less elongated in the root region than the crown region

71
Q

This is essential for root dentin formation but not for crown dentin formation; without it, odontoblasts cannot normally form even when the HERS appear normal

A

nuclear factor Ic (Nfic)

72
Q

Cementum formation starts when

A

HERS and dental follicle are in close proximity

73
Q

Both epithelial HERS and mesenchymal (dental follicle) cells participate in what, but their contribution remain unclear

A

cementum formation

74
Q

What are the molecules involved in epithelial-mesenchyme interaction

A

HERS; TGF-β, Nfic, insulin-like growth factors, Wnts, FGF

Mesenchyme; BMP and FGF

75
Q

What do the HERS cells determine regarding the roots

A

the number of roots; however many groups of HERS cells equals number of roots

76
Q

What can happen for HERS after root development

A 
Become the epithelial rest of Malassez
Apoptosis
Incorporated into cementum front
Epithelial-mesenchyme transformation
Migration to the periodontal ligament
Differentiation into cementoblasts
77
Q

This is when two or more ectodermal structures are affected

A

ectodermal dysplasia

78
Q

A mutation in this, required for normal function of FGF, BMP, and SHH, critical signaling pathways involved in epithelial-mesenchymal interaction cause ectodermal dysplasia

A

transcription factor p63

79
Q

This mutation results in a family with multiple members lacking bot maxillary premolars and mandibular 2nd premolars

A

Msx1 mutation

80
Q

What is the genetic basis for a Msx1 mutation

A

G to C transversion in the Msx1 homeodomain region, affecting its normal transcription factor function

81
Q

This mutation results in member having no molar development

A

Pax9 mutation

82
Q

What is the genetic basis for a Pax9 mutation

A

guanine insertion causing frame shift in the DNA-binding domain which affects normal transcription factor function

83
Q

This mutation results in member all having more than 8 permanent teeth undeveloped

84
Q

What is the genetic basis for an Axin2 mutation

A

missence (C to T) or insertion (G) inducing a premature stop codon resulting in the disruption of Wnt signaling (not a TF)

85
Q

What are patients with an Axin2 mutation prone to

A

colorectal polyps and cancer

86
Q

This mutation results in members having multiple missing anterior teeth (X-linked)

87
Q

What is the genetic basis of an EDA mutation

A

missence (C to G) mutation disrupting the transmembrane signaling molecule belonging to the TNF pathway (not a TF)

88
Q

What are some theories for the etiology of supernumerary teeth

A

atavism (evolutionary throwback)
tooth germ dichotomy
hyperactivity of dental lamina
genetic/environmental factors

89
Q

Most supernumerary teeth are what kind of cases

A

isolated cases; multiple supernumerary teeth are rare

90
Q

This is an autosomal-dominant skeletal displasia in clavicles, patent sutures, and fontanels, formation of Wormian bones and short stature results in supernumerary teeth and delay eruption of permanent teeth

A

cleidocranial dysplasia

91
Q

What mutation causes cleidocranial dysplasia

92
Q

What does Runx2 encode

A

a transcription factor in the mesenchyme essential for tooth development; a negative regulator for secondary teeth

93
Q

Identical Runx2 mutations showed what in supernumerary tooth formation

A

wide variaion; suggesting epigenetic and environmental factors

94
Q

This causes adenomatours polyps of the GI tract, demoed tumors, osteomas, and dentally; supernumerary teeth, impacted teeth, dentigerous cysts, etc.

A

Gardner’s syndrome

95
Q

What is the mutation that causes Gardner’s syndrome

A

APC gene mutation

96
Q

What APC deficiency mediated by

A

β-catenin (Wnt pathway)

97
Q

Does APC encode a transcription factor

May14 Oral Histology (25 decks)

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