molecular/genetic tooth development Flashcards Preview

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Flashcards in molecular/genetic tooth development Deck (71):
1

when do CNCCs start migrating

when the neural tube closes

2

where do the CNCCs migrate to

they take defined paths to the branchial arches

3

what week are branchial arches formed

week 4

4

teeth develop from which branchial arch

BA 1

5

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

precise tissue-tissue interactions

6

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

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

7

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

mesoderm provides environment for the NCC to populate

8

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

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

9

hindbrain consists of

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

10

1st BA's NCCs come from

r1-2

11

2nd BA's NCCs come from

r4

12

3rd BA's NCCs come from

r6-7

13

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

even numbered segments/rhombomeres to innervate their peripheral structures

14

trigeminal nerve supplies

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

15

facial nerve supplies

r4-5

16

glossopharyngeal supplies

r6-7

17

NCCs in each migratory stream express

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

18

Hox genes defined

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)

19

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

transcription factor which controls other gene expression

20

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

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

21

NCCs involved in tooth development

do NOT express Hox genes

22

D1x gene

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

23

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

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

24

D1x1/2 is required for the development of

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

25

D1x5/6 is required for the development of

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

26

D1x5/6 double mutants develop...

lower jaws that look just like the upper jaw

27

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

yes

28

what allows tooth development to get from stage to stage

it is precisely arranged and regulated by cell and molecular interactions

29

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

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

30

what are the 4 major signaling pathways for ectoderm derived epithelium

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

31

what is similar b/w all 4 signaling pathways

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

32

what is an enamel knot

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

33

primary enamel knot appears

at the end of the bud stage

34

what is the job of the primary enamel knot

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

35

how does the primary enamel knot disappear

cell apoptosis

36

the secondary enamel knot appears

at the locations of future molar cusps at the BELL stage

37

what is the job of the secondary enamel knot

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

what determines the cusp patterns

differential expression of signaling molecules in the EK

39

FGF fns as a

cusp activator

40

BMPs fn as a

inhibitor to regulate the formation of inter-cusp distance

41

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

1. initiation
2. morphogenesis
3. differentiation and mineralization

42

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

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

43

innervation of the teeth is from what CN

trigeminal axons

44

when do nerves enter the dental pulp

after the start of enamel formation/ bell stage

45

what expresses Sema3a

epithelium

46

what is the fn of Sema 3a

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

47

is induction from the epithelium required for root development

yes

48

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

lamini-5 and TGF-beta

49

what is nuclear factor Ic (NFIC) for

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

50

when does cementum formation start

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

51

contributions of HERs to root development

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

fates of HERS

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

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

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

54

ectodermal displasia syndrome

2 or more ectodermal structures are affected

55

what is the mutation for ectodermal displasia syndrome

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

Msx1 mutation causes

lack both maxillary premolars and mandibular 2nd premolars.

57

how is Msx1 mutated

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

58

what does Msx1 normally do

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

Pax 9 mutation causes

no molar development

60

how is Pax 9 mutated

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

61

what does Pax9 normally do

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

Axin2 mutation causes

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

63

how is Axin2 mutated

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

64

what does Axin2 normally do

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

EDA mutation causes

multiple missing anterior teeth. x-linked dominant

66

how is EDA mutated

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

67

what does EDA normally do

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

68

supernumerary teeth related to what 2 systemic conditions

1. cleidocranial dysplasia
2. gardner's syndrom

69

what causes cleidocranial dysplasia

Runx2 mutations

70

what is Runx2

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

71

gardner's syndrome is causes by

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