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Oral Histo > molecular/genetic tooth development > Flashcards

molecular/genetic tooth development Flashcards

1
Q

when do CNCCs start migrating

A

when the neural tube closes

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2
Q

where do the CNCCs migrate to

A

they take defined paths to the branchial arches

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3
Q

what week are branchial arches formed

A

week 4

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4
Q

teeth develop from which branchial arch

A

BA 1

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5
Q

development of the BA structures at the right location and time depend on…

A

precise tissue-tissue interactions

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6
Q

what is the tissue interactions b/w the NCC and the ectoderm

A

ectoderm regulates NCC cells during morphogenesis and controls the position, size and shape of the organs

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7
Q

what is the tissue interactions b/w the NCC and the mesoderm

A

mesoderm provides environment for the NCC to populate

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8
Q

what is the tissue interactions b/w the NCC and the endoderm

A

endoderm develops pharyngeal pouch generated organs (thyroid, parathyroid, and thymus)

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9
Q

hindbrain consists of

A

7 segments called rhombomeres. the NCCs here migrate in 3 streams (r1-2/r4/r6-7)

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10
Q

1st BA’s NCCs come from

A

r1-2

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11
Q

2nd BA’s NCCs come from

A

r4

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12
Q

3rd BA’s NCCs come from

A

r6-7

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13
Q

the branchiomotor nerves (nerves that supply the BA structures) exit the hindbrain only from

A

even numbered segments/rhombomeres to innervate their peripheral structures

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14
Q

trigeminal nerve supplies

A

r1-3, 1st branchial arch structures INCLUDING THE TEETH

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15
Q

facial nerve supplies

A

r4-5

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16
Q

glossopharyngeal supplies

A

r6-7

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17
Q

NCCs in each migratory stream express

A

specific Hox gene codes. So specific NCC streams have a specific Hox gene profile

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18
Q

Hox genes defined

A

a group of homeobox genes which possess a unique DNA sequence, which encodes a conservative protein segmen/homeodomain (aka a family of genes that have a specific DNA sequence that encodes for a particular protein)

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19
Q

if a Hox gene is expressed, its protein fns as a

A

transcription factor which controls other gene expression

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20
Q

NCCs that migrate to BA 1 (r1-2) are

A

Hox free. They carry the genes, but don’t express them

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21
Q

NCCs involved in tooth development

A

do NOT express Hox genes

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22
Q

D1x gene

A

homeobox gene that is expressed as transcription factors. (related to the drosophila distal-less gene). 7 members of the D1x family (1-7).

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23
Q

within the first BA, what is the job of the D1x gene

A

when expressed, it produces differences b/w the maxilla and the mandible (both derived from BA 1)

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24
Q

D1x1/2 is required for the development of

A

proximal portion of the 1st branchial arch..which is the maxillary process

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25
Q

D1x5/6 is required for the development of

A

distal portion of the 1st branchial arch..which is the mandibular process

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26
Q

D1x5/6 double mutants develop…

A

lower jaws that look just like the upper jaw

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27
Q

are Hox genes expressed in NCCs that travel to the 2nd BA

A

yes

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28
Q

what allows tooth development to get from stage to stage

A

it is precisely arranged and regulated by cell and molecular interactions

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29
Q

all tooth structures (except for enamel) are directly contibuted by

A

CNCCs that migrated to the 1st BA. CNCCs contribute to the development of the dentin, cementum and the PDL (not enamel)

30
Q

what are the 4 major signaling pathways for ectoderm derived epithelium

A
  1. BMP
  2. FGF
  3. Wnt
  4. SHH
    they are also important for the development of other ectodermal organs (hair, nails, glands)
31
Q

what is similar b/w all 4 signaling pathways

A

all of the molecules bind to cell membrane receptors and are able to regulate gene expression via intracellular pathways.

32
Q

what is an enamel knot

A

epithelial aggregates that fn as signal centers for morphogenesis and odontoblast differentiation

33
Q

primary enamel knot appears

A

at the end of the bud stage

34
Q

what is the job of the primary enamel knot

A

strongly stimulates the proliferation of adj cells. essential for bud-to-cap stage transition. (would be arrested w/o it).

35
Q

how does the primary enamel knot disappear

A

cell apoptosis

36
Q

the secondary enamel knot appears

A

at the locations of future molar cusps at the BELL stage

37
Q

what is the job of the secondary enamel knot

A

stimulates the terminal differentiation of odontoblasts at the end of the bud stage, this always occurs first at the location of the future cusp tips. also determines the number and location of the molar cusps. (not present in incisors)

38
Q

what determines the cusp patterns

A

differential expression of signaling molecules in the EK

39
Q

FGF fns as a

A

cusp activator

40
Q

BMPs fn as a

A

inhibitor to regulate the formation of inter-cusp distance

41
Q

at the cell/molecular level, development of the tooth crown can be divided into 3 major stages

A
  1. initiation
  2. morphogenesis
  3. differentiation and mineralization
42
Q

what is the difference b/w the determination of incisors vs molars

A

though that different molecular interactions are present at the anterior compared to the posterior which controls what develops where

43
Q

innervation of the teeth is from what CN

A

trigeminal axons

44
Q

when do nerves enter the dental pulp

A

after the start of enamel formation/ bell stage

45
Q

what expresses Sema3a

A

epithelium

46
Q

what is the fn of Sema 3a

A

chemorepellent for axons. so it controls the timing and patterning of tooth innervation.

47
Q

is induction from the epithelium required for root development

A

yes

48
Q

what is secreted by HERS to stimulate dental papilla cells to differentiate into apical odontoblasts

A

lamini-5 and TGF-beta

49
Q

what is nuclear factor Ic (NFIC) for

A

root dentin formation…not crown dentin. without NFIC, odontoblasts cannot form even when HERS is normal

50
Q

when does cementum formation start

A

when HERS and the dental follicle are in close proximity. Both HERS/epithelial and mesenchymal/dental follicle cells participate

51
Q

contributions of HERs to root development

A
  1. don’t respond to mesenchyme signals and do not differentiate into ameloblasts
  2. induce differentitation of odontoblasts
  3. induce the differentiation/transdifferentiate into cementoblasts
  4. determine the number of root canals
52
Q

fates of HERS

A
  1. epithelial rests of malassez
  2. apoptosis
  3. incorporated into the cementum front
  4. epithelial-mesenchymal transformation
  5. migration into PDL
  6. differentiation into cementoblasts
53
Q

are molecules involved for root development the same as those involved in crown development

A

no. HERS (FGF, Wnt, TGFbeta, NFIC, IGF). Mesenchyme (BMP, FGF)

54
Q

ectodermal displasia syndrome

A

2 or more ectodermal structures are affected

55
Q

what is the mutation for ectodermal displasia syndrome

A

t.f p63. normally required for the normal fn of FGF, BMP, and SHH (which are all required for epithelial-mesenchyme interactions) so when altered, tooth development is not normal

56
Q

Msx1 mutation causes

A

lack both maxillary premolars and mandibular 2nd premolars.

57
Q

how is Msx1 mutated

A

G–>C transversion (arg–>pro) that causes an Msx1 gene mutation

58
Q

what does Msx1 normally do

A

it is a t.f that is expressed in the mesenchyme and is involved in tooth development. mutation is at the homeodomain region affects the normal t.f protein fn.

59
Q

Pax 9 mutation causes

A

no molar development

60
Q

how is Pax 9 mutated

A

guanine insertion that causes a frame shift of the Pax 9 gene

61
Q

what does Pax9 normally do

A

it is a t.f expressed in the mesenchyme for tooth development. mutation is at its DNA binding domain which affects it as a t.f.

62
Q

Axin2 mutation causes

A

more than 8 permanent teeth underdeveloped. patients may be susceptible to colorectal polyps and cancer

63
Q

how is Axin2 mutated

A

missense C–>T or G insertion causing a premature stop codon in the Axin2 gene

64
Q

what does Axin2 normally do

A

it is expressed extensively in the mesenchyme and loss of its fn disrupts Wnt signalling for tooth development. it is NOT a t.f

65
Q

EDA mutation causes

A

multiple missing anterior teeth. x-linked dominant

66
Q

how is EDA mutated

A

have missense C–>G mutation that results in a Q to E substitution in EDA

67
Q

what does EDA normally do

A

it is a transmembrane signalling molecule that belongs to the TNF pathway. it is NOT a t.f.

68
Q

supernumerary teeth related to what 2 systemic conditions

A
  1. cleidocranial dysplasia

2. gardner’s syndrom

69
Q

what causes cleidocranial dysplasia

A

Runx2 mutations

70
Q

what is Runx2

A

t.f expressed by the mesenchyme that is essential for tooth development. positive regulator for primary teeth but negative regulator for secondary teeth

71
Q

gardner’s syndrome is causes by

A

APC mutation. mediate by the beta catenin pathway/wnt pathway

Oral Histo (12 decks)

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