Molecular and Genetic Basis

Question 1

Cranial Neural Crest Cells

Answer 1

• formed at the back of neural tube (E22)
• start migrating laterally when the neural tube closes
• migrate a long distance through a defined path to reach the branchial arches
• they are stem cells

Question 2

teeth develop in what branchial arch?

Answer 2

1

Question 3

what can stem cells do?

Answer 3

1. self renewal

2. differentiate into a variety of different cells

Question 4

how do NCC interact with all three germ layers?

Answer 4

1. ectoderm regulates ncc during morphogenesis and controls the position, size and shape of the organs
2. mesoderm provides an environment for the NCC to populate
3. endoderm pharyngeal pouch organs, thyroid, parathyroid and thymus

Question 5

what NCC migrate to the branchial arch 1,2 and 3?

Answer 5

hindbrain rhombomeres r1-2 to 1, r4 to 2 and r6,7 to 3

Question 6

where do the axons for the rhombomeres come from?

Answer 6

trigeminal nerve for r1-3, facial nerve for r4-5 and glosopharyngeal nerve for r6-7

Question 7

what happens to rhombomeres 5 and 7?

Answer 7

most of the cells undergo apoptosis and wont migrate creating a “separater”

Question 8

Hox genes

Answer 8

a group of homeobox genes that posses a unique homeobox (DNA sequence) that encodes a conservative homeodomain.

• different Hox genes in each rhombomere
• the protein product of Hox gene expression is a transcription factor

Question 9

how are the ncc migrating to branchial arch 1 and 2 different?

Answer 9

Ba1 does not express hox genes (has them though) and Ba2 begins to express hox genes

Question 10

Do NCC involved in tooth development express hox?

Answer 10

NO

Question 11

what homeobox gene differentiate the development of the maxilla and mandible of Ba1?

Answer 11

Dlx gene

• Dlx1/2 for maxilla and Dlx5/6 for mandible
• homeobox gene that express transcription factors

Question 12

what structures do NCC DIRECTLY contribute to ?

Answer 12

dentin, cementum, pulp and PDL

**NOT ENAMEL

Question 13

what are the 4 major signaling pathways (bind outside the cell) are produced by epithelium to regulate mesenchyme?

Answer 13

BMP (bone morphogeneic), FGF (fibroblast growth factor), Wnt and SHH (sonic hedgehog)
**bind outside and regulate gene expression inside the cell

Question 14

primary enamel knot

Answer 14

• appears at end of bud stage
• closely interacts with mesenchyme
• strongly stimulates proliferation of the adjacent cells
• *essential for the bud to cep stage transition, arrested development if not present
• disappears by apoptosis

Question 15

secondary enamel knot

Answer 15

• appears at the location of future MOLAR cusps at the bell stage
• stimulates terminal differentiation of ODB at the end of the bud stage, which occurs first at the cusp tips
• *determines location and number of molar cusps
• not present in incisors

Question 16

what causes the cusp patterns?

Answer 16

differential expression of signaling molecules in the enamel knots
FGF is a cusp activator and BMP (and maybe SHH) function as inhibitors to make the inter-cusp distance

Question 17

what are the stages of tooth crown development?

Answer 17

initiation, morphogenesis and differentiation and mineralization

Question 18

what cranial nerve innervates teeth?

Answer 18

pioneer trigeminal axons penetrate into the dental pulp at the start of enamel formation (bell stage)

Question 19

Sema3A

Answer 19

chemorepellent for axons, controlling the pattern and timing of tooth innervation
**produced by the epithelium

Question 20

explain root development

Answer 20

HERS secretes lamini-5 and TGF-Beta that promotes the formation of apical ODB on the papilla side, ODB less elongated than crown region and Nfic needed for ODB to normally form (even in the presence of HERS)
**epithelium NOT present in the final root, but epithelium induces root formaiton

Question 21

are the molecules in crown epi-mesenchyme interaction the same as in the root?

Answer 21

NO!

Question 22

What are the the contributions of HERS?

Answer 22

• do not respond to mesenchyme signals and dont become ameloblsts
• differentiate ODB and cementoblasts
• transdifferentiaton into cementoblasts
• determines root number

Question 23

what are possible fates of HERs after root development?

Answer 23

epithelial rest of malassez, apoptosis, incorporated into cementum, epi-mes transformation, migration to the PDL and differentiation into cementoblasts

Question 24

ectodermal displasia

Answer 24

2 or more ectodermal structures are affected

• (TF) p63 mutation
• critical for BMP, FGF and SHH pathways
• have involve hair

Question 25

Msx1 mutation

Answer 25

-gene codes for a transcription factor
-not as severe because twin gene MSX2 can do stuff
(G to C transversion in gene)
(molars and premolars)
-at homeodomain region

Question 26

Pax9 mutation

Answer 26

-no molar develop
-guanine insertion (frame shift)
-gene codes for TF
at DNA binding domain

Question 27

Axin2 mutation

Answer 27

• more than 8 perm teeth undeveloped
• missense or insertion mutation that codes a stop
• gene does NOT code for A TF (signaling molecule)
• prone to polyps and cancer
• mutation disrupts Wnt signaling

Question 28

EDA mutations

Answer 28

• multiple missing ant. teeth (x-linked)
• missense mutation
• transmembrane signaling molecule
• disrupts the TNF pathway

Question 29

theories for supernumery teeth

Answer 29

• atavism (evolution)
• tooth germ dicotomy
• hyperactive dental lamina
• genetic and environmental factors

Question 30

Cleidocranial dysplasia syndrome

Answer 30

• autosomal dominant
• Runx2 encodes a TF for the mesenchyme
• RUnx2 is a positive regulator for primary teeth and a negative regulator for secondary teeth
• shows wide variation among experiments (genetic and environmental factors control)

Question 31

Gardners syndrome

Answer 31

• GI tract polyps, tumors, supernumery teeth, impacted teeth and dentigerous cysts
• caused by APC mutation (loss of function) and B-catenin gain of function
• signaling molecule