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Oral Histology > 5 Molecular & Genetic Basis of Tooth Development > Flashcards

5 Molecular & Genetic Basis of Tooth Development Flashcards

1
Q

Final fate of NCC?

A

Odontoblasts or cementoblasts via ectomesenchymal cells.

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2
Q

Teeth are only developed in…?

A

the 1st branchial arch`

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3
Q

Stem cells (ie NCCs) can…

A

replicate (via asymmetric division) or differentiate into many cell types.

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4
Q

NCC (4th germ layer) + ectoderm, endoderm, mesoderm. Role of each “germ”?

A 
Ectoderm = regulates NCC cells during morphogenesis, controls position, size, and shape of organs.
Mesoderm = provides environment.
Endoderm = develops pharyngeal pouch-generated organs (thyroid, parathyroid, and thymus)
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5
Q

1. NCCs form well-organized migratory streams to the branchial arches. BA?

A 
Via hindbrain rhmobomeres.
*1st BA: r 1, 2
2nd BA: r 4
3rd BA: r 6, 7
r 3 & 5 degenerate.
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6
Q

1. NCCs form well-organized migratory streams to the branchial arches. CN?

A

*CN V: r 1-3
CN VII: r4-5
CN IX: r6-7

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7
Q

2. NCCs in each migratory stream express specific Hox gene codes. Def/role?

A

Hox genes = a group of homeobox genes, which possess a unique homeobox (DNA sequence) –> homeodomain (protein segment) which acts as TF.

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8
Q

2. NCCs in each migratory stream express specific Hox gene codes. Which BAs express Hox genes?

A

1st BA is Hox-free (carry genes but don’t express them).

2nd BA begins Hox expression

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9
Q

3. Within each BA, specific Dlx genes are expressed to produce regional differences (ie b/w maxilla and mandible). Def/role?

A

Dlx = another homeobox gene –> TF.
7 members of family.
Dlx 4, 7, 8, 9 are same.

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10
Q

3. BA 1 Dlx 1/2?

A

maxillary (proximal) process

Double mutants lack all maxillary molars (mandibular molars unaffected)

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11
Q

Proper development of maxillary/proximal process requires?

A

Dlx 1/2

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12
Q

3. BA 1 Dlx 5/6?

A

mandibular (distal) process

-/- mutants develop lower jaws that are mirror images of upper jaws

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13
Q

Proper development of mandibular/distal process requires?

A

Dlx 5/6

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14
Q

*Among cells required for tooth development, which ones have an NCC origin?

A

Odontoblasts and cementoblasts (via ectomesenchyme). NOT ameloblasts.

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15
Q

*NCCs migrated to the 1st BA are from which hindbrain rhombmeres?

A

r 1 + 2

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16
Q

*Which homeobox gene differentiates NCCs migrated to different BA?

A

Hox genes

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17
Q

*Which homeobox gene differentiates development of the maxillary and mandibular processes within the first BA?

A

Dlx genes

max: Dlx 1+2
mand: Dlx 5+6

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18
Q

Origin of tissue-tissue interactions?

A

Initiated by epithelium, followed by epithelium-mesenchyme interaction through the entire process of tooth development.

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19
Q

Origins of enamel and dentin?

A

Ectoderm –> epithelium –> ameloblasts/enamel

NCC/mesoderm –> mesenchyme –> odontoblasts –> dentin

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20
Q

Ectoderm-Derived Epithelium Signaling Pathways - 4 molecule names?

A

BMP: bone morphogenic protein
FGF: fibroblast growth factor
Wnt: wingless (drosophila) & int (mouse)
SHH: sonic hedge hog

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21
Q

Ectoderm-Derived Epithelium Signaling Pathways - mechanism of action?

A

Molecules bind membrane receptors –> impact gene regulation (via varied intracellular pathways). Also important for ectodermal organs (ie hair, nails glands)

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22
Q

Enamel knots definition

A

Epithelial aggregates function as signal centers for tooth morphogenesis & odontoblast differentiation.

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23
Q

Primary enamel knots

A

Bud –> cap transition in ALL teeth.
Stimulate proliferation of adjacent cells.
Disappear by apoptosis.

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24
Q

Secondary enamel knots

A

Determine number & location of molar cusps (NOT in incisors).
Stimulate terminal differentiation of odontoblasts.

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25
Q

Signaling molecules in enamel knots?

A

FGF = cusp activator
BMP, SHH = cusp inhibitor
to regulate formation of inter-cusp distance.

26
Q

Cranial CNNs contribute to…

A

Formation of all tooth structures (dentin, cementum, pulp, PDL, but NOT enamel)

27
Q

Mesenchyme Signaling Molecules?

A

Signaling molecules: BMP, FGF, Wnt, inhibitors (but not SHH)

Transcription factors: Msx1/2, Dlx1/2, Pax9, Gli2/3, Runx2, Barx1, etc.

28
Q

steps of development of a tooth crown

A
  1. initiation
  2. morphogenesis
  3. differentiation and mineralization
29
Q

Tooth identify determination

A

Anterior (distal): BMP4 –> MSx 1/2

Posterior (proximal): FGF –> Barx1, Dlx2, Lhx6/7

30
Q

Epithelium expresses…into mesenchyme?

A

Sema3A = serves as chemorepellant for axons, thus controlling the timing and patterning of tooth innervation

31
Q

*What are the cell and tissue origins for tooth structures?

A

Most are mesenchyme (enamel is epithelium)
Ectoderm –> epithelium –> ameloblasts/enamel
NCC/mesoderm –> mesenchyme –> odontoblasts –> dentin

32
Q

*What four major signaling molecules are produced by the epithelium?

A

BMP, FGF, Wnt, SHH

33
Q

*What are the common transcription factors produced by the mesenchyme?

A

Transcription factors: Msx1/2, Dlx1/2, Pax9, Gli2/3, Runx2, Barx1, etc.

34
Q

What are the common signaling molecules produced by the mesenchyme?

A

Signaling molecules: BMP, FGF, Wnt, inhibitors (but not SHH)

35
Q

*What are the main characteristics and functions of the two sets of enamel knots?

A

1˚: bud –> cap transition for all teeth.

2˚: location and number of cusps for molars

36
Q

*At the cellular and molecular level, crown development is divided into what 3 stages?

A

IM DM

  1. Initiation
  2. Morphogenesis
  3. Differentiation & Mineralization
37
Q

*Innervation of tooth is from which NC, and when do the nerve fibers first enter the pulp area?

A

CN V, enters after the start of enamel formation

38
Q

HERS

A

After crown development nearly complete, epithelial root sheath grows apically between two mesenchymal regions (dental papilla & follicle).

39
Q

Epithelium and root development?

A

No enamel in root, but induction from epithelium is required for root development.

40
Q

HERS induces…

A

HERS induces dental papilla cells to differentiate into odontoblasts.

41
Q

HERS uses…?

A

Differentiation via lamini-5 and TGF-beta.

42
Q

Nfic?

A

Nuclear factor Ic

Essential for root dentin (along with HERS), but not crown dentin formation

43
Q

Cementum formation starts when…

A

HERS (epithelial) and dental follicle (mesenchyme) cells are in close proximity

44
Q

Epithelium-Mesenchyme Interaction during Root Development

A

HERS: TGF-b, Nfic, insulin-like GF, Wnts, FGF
Mesenchyme: BMP, FGF
Some overlap with crown develpment

45
Q

Two mechanisms to root cementum formation?

A

1st: directly from dental follicle
2nd: HERS “trans-differnetiated” into cementoblasts.

46
Q

Contributions of HERS to root development

A
  • HERS do not –> ameloblasts/enamel.
  • HERS do not respond to signals from the mesenchyme and differentiate into ameloblasts.
  • Induce diff. of odontoblasts
  • Induce diff. of cementoblasts, OR HERS cells may transdifferentiate into cementoblasts.
  • Determine # of roots
47
Q

Fates of HERS

A
  • Become epithelial rest of Malassez
  • Apoptosis
  • Incorporated into the cementum front
  • E-M transformation
  • Migration to PDL
  • Differentiation into ameloblasts
48
Q

*What are the tissue and cell origins for root dentin and cementum?

A

Mostly mesenchyme - some cementum from HERS (epi) via transdifferentation

49
Q

*Is epithelium required to induce the formation of odontoblasts to root dentin and cementumblasts to cementum?

A

Yes! Epi required, even though no enamel in root.

50
Q

*Are molecules involed in E-M interaction for root development the same as those involved in crown development?

A

No, some overlap

51
Q

What can happen to HERS after root development?

A

Multiple possibilities (induce, transdifferentiate, apoptosis)

52
Q

ectodermal dysplasia syndrom

A

2+ ectoderm structures

mutation of TF p63 (critical for FGF, BMP, SHH epi-mes interaction)

53
Q

Msx1 mutation

A

No max premolars, mand 2nd premolars
G–>C transversion (arginine –> proline)
TF in mesenchyme
Mutation in homeodomain region

54
Q

Pax9 mutation

A

no molar development
guanine insertion
TF in mesenchyme
Mutation in DNA-binding domain

55
Q

Axin2 mutation

A 
8+ perm teeth underdevelopd
Missense (C-->T), insertion (G)
Premature stop codon
Disrupts Wnt signaling to mesenchyme
Colorectal polyps and cancer
56
Q

EDA mutation

A 
multiple missing anterior teeth
X-linked dominant
Missense C--G ==> Q to E substitution in EDA
Transmembrane signaling molecule
TNF pathway
57
Q

Theories of etiology of supernumerary teeth

A

tooth germ dichotomy

genetic and environmental factors

58
Q

System conditions –> supernumerary teeth

A

Cleidocranial dysplasia

Familial adenomatous polyposis (Gardner’s syndrome)

59
Q

Cleidocranial Dysplasia

A

Supernumerary, delayed/impact perm.

Runx2 TF mutation

60
Q

Gardner’s Sydnrome

A

Supernumerary, impact, dentigerous teeth
Apc mutation through Wnt signaling pathway
Apc loss-of-function, B-catenin gain-of-function

61
Q

*Gene mutations related to missing teeth?

A

TF: Msx1, Pax9, p63 (BMP, FGF, SHH)
Signal: Axin2 (via Wnt), EDA (via TNF)

62
Q

*Gene mutations related to supernumerary?

A

TF: Runx2
Singal: Apc (via Wnt)

Oral Histology (9 decks)

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