Ex 2- Molecular + Genetic Basis of Tooth Development-- Sun Flashcards

1
Q

Cranial neural crest cells the _____ germ layer

A

fourth

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2
Q

_____ _____ _____ cells (NCC) are formed at the _____ of the neural tube and start migrating when the neural tube closes

A

Cranial neural crest

back

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3
Q

NCC migrate a long distance through defined paths to reach the ______ _____

A

branchial arches

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4
Q

NCC cells are ____ cells

A

stem

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5
Q

Branchial arches (pharyngeal arches) are ridges formed on the sides of head and neck at embryo week __

A

4

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6
Q

Teeth are only developed in the _____ branchial arch

A

first

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7
Q

What are the 2 fates of a stem cell?

A
  1. replicate itself (self renewal)

2. Differentiate into varied types of mature cells

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8
Q

What are the 2 divisions of stem cells?

A

Symmetric (same)- parent cell

Asymmetric (different)- differentiated cell

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9
Q

NCCs are _____-____ stem cells

A

multi-potent

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10
Q

NCCs can differentiate to form ectomesenchymal cells which ultimately from ______ and _______

A

odontoblasts

cementoblasts

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11
Q

Embryonic development of branchial arch structures, including odontogenesis at the right location and time relies on complicated but precise ______-_____ interaction

A

tissue-tissue

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12
Q

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

A

Ectoderm- NCC

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13
Q

______ - _____develops pharyngeal pouch generated organs: thyroid, parathyroid, and thymus

A

Endoderm- NCC

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14
Q

______ - _____ provides environment for NCC cells to populate

A

Mesoderm-NCC

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15
Q

NCCs form well-organized _______ ______ to the branchial arches

A

migratory streams

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16
Q

NCCs for the first branchial arch are from hindbrain rhombomeres r__-__

A

1-2

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17
Q

How many rhombomeres are there in the hindbrain?

A

7

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18
Q

Hindbrain-derived neural crest cells migrate in ___ streams: Arch 1, 2, 3

A

3

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19
Q

1st branchial arch is from rhombomeres r __ - __

A

1-2

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20
Q

2nd branchial arch is from rhombomeres r __

A

4

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21
Q

3rd branchial arch is from rhombomeres r __ - __

A

6-7

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22
Q

Rhombomeres ___ and ___ undergo apoptosis creating a barrier

A

3 and 5

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23
Q

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

A

even

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24
Q

_______ nerve is associated with r __-__; 1st branchial arch structures including ______

A

Trigeminal (V)
1-3
teeth

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25
Q

______ nerve is associated with r4-5 the 2nd branchial arch

A

Facial (VII)

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26
Q

_______ nerve is associated with r6-7 the 3rd branchial arch

A

Glosopharyngeal (IX)

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27
Q

NCCs in each migratory stream express specific _____ ____ codes

A

Hox gene

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28
Q

_____ ____ are 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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29
Q

If a Hox gene is expressed, its protein product functions as a _______ ______ which controls other gene expression

A

transcription factor

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30
Q

NCCs involved in tooth development (1st branchial arch) do NOT express _____ _____. They carry the genes but don’t express them

A

Hox genes

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31
Q

NCCs that migrate to the ___ branchial arch start expressing Hox gene

A

2nd

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32
Q

Within the first branchial arch, specific ____ ____ codes are expressed to produce differences between he maxilla and mandible

A

Dlx gene

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33
Q

Dlx genes another ________ gene expressed as _____ ______. 7 members in family. 4,7,8,9 are same gene

A

homeobox

transcription factors

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34
Q

Dlx __/__ combination is required for development of the proximal portion of first branchial arch (maxillary process)

A

1/2

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35
Q

Dlx 1/2 double mutants lack ALL _______ _____ while all mandibular structures are not affected

A

maxillary molars

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36
Q

Dlx __/__ combination is required for development of the distal portion of 1st branchial arch (mandibular process)

A

5/6

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37
Q

Dlx 5/6 double mutants develop lower jaws like mirror images of the ________ jaw

A

upper

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38
Q

Normal tooth development is a process with precisely arranged/regulated _____ and ____ interactions

A

cell and molecular

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39
Q

Interaction between the epithelium and the _______ is through the entire process of tooth development

A

mesenchyme

40
Q

Cranial neural crest cells directly contribute to the development of dentin, cementum, pulp and periodontal ligament but not to _____

A

enamel

41
Q

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

A
  • BMP; bone morphogenic protein
  • FGF: fibroblast growth factor
  • Wnt: wingless
  • SHH: sonic hedgehog
42
Q

All four molecules (BMP, FGF, Wnt, SHH) bind to the _____ ______ ____ and eventually impact on gene regulation through varied ______ _______

A

cell membrane receptors

intracellular pathways

43
Q

These molecular signals are also important for the development of other _______ organs such as hair, nails, and glands

A

ectodermal

44
Q

______ ____ are epithelial aggregates that function as ______ ______ for tooth morphogenesis and odontoblast differentiation

A

enamel knots

signaling centers

45
Q

_______ enamel knot appears at the end of the bud stage and is essential for bud-to-cap stage transition, without it, tooth development will be arrested

A

primary

46
Q

_______ enamel knot appears at the locations of future molar cusps at the bell stage and determine the _____ and ____ of molar cusps

A

secondary
number
locations

47
Q

The ______ enamel knot closely interacts with the mesenchyme

A

primary

48
Q

The ______ enamel knot stimulates terminal differentiation of odontoblasts at the end of the bud stage, which always occurs first at the location of future cusp tips

A

secondary

49
Q

The ________ enamel knot stimulates proliferation of adjacent cells

A

primary

50
Q

The ______ enamel knot disappears by cell apotosis

A

primary

51
Q

The ______ enamel knot is not present in incisors

A

secondary

52
Q

Differential expression of signaling molecules in the enamel knots determine _____ patterns

A

cusp

53
Q

_____ may function as a cusp activator while ____ (possibly Shh also)may function as the inhibitor to regulated the formation of _____-_____distance

A

FGF
BMP
inter-cusp

54
Q

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

A

BMP
FGF
Wnt
+ their inhibitorss

55
Q

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

A
Msx 1/2
Dlx 1/2
Pax9
Gli 2/3
Runx2
Barx1
56
Q

At the cell and molecular level, the development of tooth crown can be divided into what 3 major stage?

A
  1. Initiation
  2. Morphogenesis
  3. Differentiation + Mineralization
57
Q

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

A

BMP4
Msx1
Msx2

58
Q

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

A

FGF
Barx1
Dlx2
Lhx6/7

59
Q

Innervation of the tooth is from what cranial nerve?

A

CN V (Trigeminal)

60
Q

Pioneer trigeminal axons penetrate into the dental pulp after the start of enamel formation during the _____ stage

A

Bell

61
Q

______ serves as a chemorepellent for the axons, thus controlling the timing and patterning of tooth innervation

A

Sema3A

62
Q

Through the epithelial-mesenchymal interaction, epithelium expresses what into mesenchyme?

A

Sema3A

63
Q

After the crown development is nearly complete, the ______ ______ _____ grows apically between the 2 mesenchymal regions; dental papilla + dental follicle

A

Hertwig’s root sheath (HERS)

64
Q

After HERS formation _______ _____ appear adjacent to the HERS on the papilla side

A

apical odontoblasts

65
Q

Although enamel is not present in the final root, induction from the ______ is required for root development

A

epithelium

66
Q

______ develops before ______ in terms of parts of the tooth

A

crown

root

67
Q

HERS induces dental papilla to differentiate into _____ _____

A

apical odontoblasts

68
Q

________ secreted by HERS induces odontoblast differentiation

A

lamini-5 + transforming growth factor-beta (TGF-B)

69
Q

_______ _____ ___ is essential for root dentin formation but not for crown dentin formation. Without this odonotblast cannot develop normally even when HERS is normal

A

Nuclear factor Ic (Nfic)

70
Q

Odontoblasts in the _____ region are much less elongated than those in the _____ regions

A

root

crown

71
Q

Cementum formation starts when ____ and ____ ______ cells are in close proximity (relative contributions unclear)

A

HERS

dental follicle

72
Q

What molecules are involved in epithelial-mesenchyme interaction?

A
  • HERS: TGF-B, Nfic, Insulin like growth factors, Wnts, FGF

- Mesenchyme: BMP, FGF

73
Q

HERs determine the ______ of roots

A

number

74
Q

_____ do not respond to signals from the mesenchyme an do not differentiate into ameloblasts

A

HERs

75
Q

Most molecules involved in crown and root development are _______

A

different

76
Q

______ ______ syndrome is when two or more ectodermal structures are affected

A

Ectodermal dysplasia

77
Q

Mutations in transcription factor _____ causes ______ ____ but normal function is requried fro the normal function of FGF, BMP, SHH, critical signaling pathways involved in epithelial-mesenchymal interaction

A

p63

ectodermal dysplasia

78
Q

_____ mutation results in multiple family members lacking both maxillary premolars and mandibular 2nd premolars

A

Msx1

79
Q

Msx1 mutation is caused by __ to ___ transversion in the homeodomain region affecting its normal transcription factor function

A

G

C

80
Q

_____ mutations cause people to have no molar development and is caused by a _______ insertion that causes a frame shift in the DNA binding domain affecting its normal transcription factor function

A

Pax9

guanine

81
Q

______ mutations cause affected members to have more than 8 permanent teeth underdeveloped

A

Axin2

82
Q

Axin2 mutations are caused by missence (C–>T) or insertion (G) mutations that introduce a premature _____ codon in the gene

A

stop

83
Q

Loss of Axin2 function disrupts the ______ signaling but Axin2 does NOT function as a transcription factor. Prone to colorectal polyps + cancer

A

Wnt

84
Q

____ mutation causes multiple missing anterior teeth (__-linked dominant)

A

EDA

X

85
Q

EDA muation is caused by missence (C–>G) resulting in Q to E substitution disrupting the transmembrane signaling molecule belonging to the ____ family but does not function as a transcription facotr

A

TNF

86
Q

What are the theories of etiology of supernumerary teeth?

A
  • Atavism
  • Tooth germ dichotomy
  • Hyperactivity of dental lamina
  • Genetic + environmental factors
87
Q

Most supernumerary teeth are isolated cases. ______ supernumerary teeth are rare but can happen in certain ______ conditions

A

Multiple

systemic

88
Q

______ _______ syndrome 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

89
Q

_______ mutations causes clleidocranial dysplasia and encodes a transcription factor

A

Runx2

90
Q

Runx2 is a ______ regulator of primary teeth and a _____ regulator of secondary teeth

A

positive

negative

91
Q

Identical Runx2 mutations showed what in supernumerary tooth formation

A

wide variation: suggesting epigenetic + environmental factors play a role

92
Q

_______ syndrome causes adenomatours polyps of the GI tract, desmoid tumors, osteomas. Dental anomalies: supernumerary teeth, impacted teeth, dentigerous cysts

A

Gardner

93
Q

____ gene mutation causes Gardners’s syndrome is a signaling molecule NOT TF

A

APC

94
Q

APC deficiency is mediated by ___-____

A

B-catenin (wnt pathway)

95
Q

What genes encode transcription factors?

A

Msx1
Pax9
p63
Runx2

96
Q

What genes encode signaling molecules?

A

Axin2 (Wnt pathway)
EDA (TNF pathway)
Apc (Wnt pathway)

97
Q

What gene mutation are related to supernumary teeth?

A
  • Runx2- Cleiodocranial dysplasia syndrome

- Apc- Gardner’s sydrome