OE L12 Tooth Specification and Crown Development

Question 1

Which cells and structure form the jaws?

Answer 1

• Neural crest cells from posterior midbrain migrate to mandibular and maxillary processes (branchial arch 1)
• These processes later develop into the jaws

Question 2

What happens if Hoxa-2 gene is knocked out?

Answer 2

Pharyngeal arch 1 structures are unaffected, but phayngeal arch 2 structures become arch 1 structures.

Question 3

Are hox genes expressed in the head region?

Answer 3

No Hox gene expression in head region (absence of Hox is relevant to identifying the 1st pharyngeal arch). But there is expression of other homebox genes in the head.

Question 4

What homeobox-containing genes are involved in patterning of dentition?

Answer 4

• Barx
• Dlx
• Lhx
• Pitx
• Msx

Question 5

What are the role of the Dlx genes?

Answer 5

• Define a proximal-distal axis
• Define which jaw structures form (maxilla and mandible)
• Knocking out such genes changes jaw shape and size

Question 6

What 3 pairs of Dlx genes are relevant to the head?

Answer 6

Dlx1/2
Dlx5/6
Dlx3/7

Question 7

Which structure controls tooth morphogenesis?

Answer 7

The dental papilla.
Has a key role in epithelial-mesenchymal interactions responsible for tooth morophogenesis.

E.g. incisor enamel organ + molar papilla = molariform tooth
Molar enamel organ + incisor papilla = single cusp tooth

Question 8

Information about tooth position is contained where?

Answer 8

Firstly in the oral epithelium, then later transferred to the ectomesenchyme.

Question 9

What signalling restricts regions of mesenchyme that can express genes?

Answer 9

FGF8 signalling.
Only regions of mesenchyme adjacent to FGF8 expression can respond.
Mesenchyme can signal to oral epithelium, power shift from OE to mesenchyme in controlling tooth formation.

Question 10

What is the odontogenic homeobox code?

Answer 10

Different combinations of odontogenic homeobox transcription factors are expressed at distinct times in spatially restricted areas of ectomesenchyme of the developing jaws.

This leads to distinct molecular fields leading to distinct tooth type and morphology.

Question 11

Give examples of homeobox genes involved in tooth specification.

Answer 11

• Dlx1/2
• Msx2
• Barx1
• Alx3
• Msx1

Question 12

What signals establish the molecular fields of the odontogenic homeobox code?

Answer 12

FGF-8 and BMP-4
expression establish molecular fields.
They induce expression of homeobox transcription factors in underlying mesenchyme and establishes spatial info that determines tooth type.

Question 13

Which genes control tooth type in the maxilla?

Answer 13

• Incisors: Msx1 and Alx3
• Canines and premolars: Msx1 and Msx2
• Molars: Dlx1 and Dlx2

Question 14

Which genes control tooth type in the mandible?

Answer 14

• Incisors: Msx1 and Alx3
• Canines and premolars: Msx1 and Msx2
• Molars: Barx1

Question 15

Why does only one row of teeth form in each jaw? What prevents multiple rows of teeth forming?

Answer 15

• Anatomical boundary on the buccal side: the vestibular lamina (acts as natural barrier)

Question 16

Why do extra rows of teeth not form on the lingual aspect of the jaws?

Answer 16

• Osr2 transcription factor is expressed in odontogenic mesenchyme on the lingual side
• Suppresses BMP-4/Msx1 signaling pathway
• Therefore molecular fields cannot be formed in these regions

Question 17

What signalling pathway drives tooth bud formation?

Answer 17

• Shh signalling
• Found at embryonic day 11.5 in the tooth primordium
• Induces thickening of ectoderm to form tooth buds

Wnt-7b is a negative regulator of Shh and regulates tooth bud formation and isolates buds to specific areas along arch.

Question 18

Why does cap stage mark a key event in crown formation?

Answer 18

• At cap stage the enamel knot forms
• Enamel knot is formed from differentiated IEE cells and acts as a transient signalling centre
• Primary enamel knot drives folding and growth of epithelium key to tooth shape
• Signalling molecules from primary enamel knot subsequently induce formation of secondary enamel knots at sites of cusps in molar teeth

Question 19

What drives the transition from bud to cap stage of tooth development?

Answer 19

Signalling between epithelium and underlying mesenchyme tissue

Question 20

Give examples of signalling factors expressed by the enamel knot.

Answer 20

• BMPs
• Shh
• FGFs
• Wnts

Question 21

What signalling controls tooth number?

Answer 21

Wnt and BMP signalling

• Ectodin is a negative regulator of BMP and Wnt signalling and prevents inappropriate signalling
• Defects in ectodin causes supernumerary teeth

Question 22

What important transmembrane protein regulates epithelial differentiation?

Answer 22

Ectodysplasin (Eda)

Question 23

Where is Edar found?

Answer 23

Edar is only found in the enamel knot.

Question 24

What does Eda-Edar signalling control?

Answer 24

• Size of dental placode

- Reprogrammes fate of epithelial cells

Question 25

Describe hypohidrotic ectodermal dysplasia.

Answer 25

• Misshapen teeth
• Oligodontia
• Affects almost all ectodermal appendages
• Lack of sweat and sebaceous glands

Question 26

What are the 3 main type of HED?

Answer 26

• X-linked HED (Eda effected)
• Autosomal HED (Edar effected)
• Anhidrotic ectodermal dysplasia with immune deficiency (NEMO effected)

Question 27

What molecules are activators and inhibitors of crown shape regulation?

Answer 27

• BMP-4 acts as the activator. Induces enamel knot formation (each knot = 1 cusp)
• Inhibitors are Shh and FGFs. They repress knot formation and prevent activator expression.

Question 28

What is tooth agenesis?

Answer 28

• Absence of 1 or more permanent teeth.
• Frequent occurence.
• Commonly due to haploinsufficiency of Msx1 and Pax9.
• Usually the last in a series that fails to form (e.g. lateral incisor, 2nd premolar, 3rd molar)- because the molecular field gets smaller and the tooth to fall off will be the last one.