Signalling pathways in tooth development

Question 1

How do we know that cells in the teeth communicate?

Answer 1

Culturing oral ectoderm and mesenchyme and no tooth will be formed.
These two tissues need to be adjacent to form a tooth and they communicate with each other.

Question 2

Signals from where control tooth initiation?

Will these tissue combinations produce a tooth?

1. Oral ectoderm and odontogenic mesenchyme 1st BA
2. Isolation of the two above
3. Oral ectoderm and non-odontogenic mesenchyme
4. Non-oral ectoderm and odontogenic mesenchyme 1st BA

Answer 2

Oral ectoderm

1. Yes
2. No
3. Yes
4. No

Question 3

Where is the information for communication between tooth tissue?
Where is the information for the specific tooth structure kept?

Answer 3

Oral ectoderm

Mesenchyme

Question 4

Why do we go from a homeogenesis cell population to cells with different properties?

Answer 4

Teeth contain the same genetic information but express different genes.

Question 5

What gene is expressed in the mesenchyme of a tooth?

Answer 5

Pax9.

Question 6

What are the 3 ways these cell communicate?

Answer 6

1. Diffusion
2. Gap junction
3. Direct contact

Question 7

Give the four steps to communication via secreted molecules

Answer 7

1. Production and release of secreted factors (signals)
2. Diffusion of signals to the target
3. Detection of the signal by a receptor on the target cell
4. Change in gene expression/cell behaviour (shape/movement) in the target cell.

Question 8

What are 4 common growth factors in teeth called?

Answer 8

• Sonic hedgehog
• Wnts
• FGFs (Fibroblast Growth Factor)
• BMPs (Bone morphogenetic Protein)

Question 9

Signals are converted to responses in the cell in three stages…

Answer 9

• The same signal can be interpreted differently by different cells
• Leads to transcription causing certain protein production
• Always same signals in tooth development used in different cells and at different points in development.

Question 10

What is the outcome of secreted molecules?

Answer 10

RNA molecules is translated into proteins. These in the cells then can be sent to all these places in the cell and act as ligands.
Cells can then excrete growth factors.

Question 11

What two signals types happen between the epithelium and mesenchyme?

Answer 11

Sequential and reciprocal

Question 12

Give three examples of when epithelial-mesenchymal cell interactions occur?

Answer 12

• Patterning of the dentition
• Tooth initiation
• Beginning of tooth morphogenesis

(in chronological order)

Question 13

Gives two details on the homeodomain transcription factors

Answer 13

Prior to any morphological sign of tooth development.

Patterning of the dentition.

Question 14

Information to form a tooth - contained in —-.

Tooth shape and type info is contained in —-.

Answer 14

Epithelium

Mesenchyme

Question 15

When are mesenchymal signals established?

Answer 15

Prior to tooth development.

Molecules within the ectoderm will be secreted in different area.

Question 16

What growth factor is secreted with molars and which with incisors with mesenchymal signals?
Where do these molecules diffuse?

Answer 16

Fibroblast growth factors with molars and bone morphogenetic protein with incisors.

These diffuse into underlying mesenchyme and bind there.

Question 17

What part of the tooth in molars and incisors are the genes present?

Answer 17

Molars - outer edges of tooth

Incisors - centre of tooth

Question 18

What happens to some transcription factors in the odontogenic homeobox code?

Answer 18

They overlap

Question 19

Explain the shh signalling pathway

Answer 19

Initiation - determination of the sites of tooth development.

Shh binds to the receptor called PTCH1. This moves to the cytoplasmic membrane to activate GLI molecules which move inside the nucleus and activate Shh target genes.

Shh stimulates the cells to proliferate to go from a thick epithelium to the tooth bud.

Question 20

What happens if there is no Shh signalling?

Answer 20

Arrest of tooth development

Question 21

What do Wnt/Shh interactions control?

Answer 21

Dental epithelium boundaries. Within the epithelium there is a transcription factor which is a combination of Shh and Wnt-7b.

If you express Wnt-7b, the epithelia is lost. These do not form anymore. This prevents the formation of teeth.

Question 22

Explain BMP signalling that occurs

Explain what happens with BMP and without it

Answer 22

Bud stage - beginning of tooth morphogenesis.

Receptor 1 recruits receptor 2 and this group is phosphorylated.
BMP signalling is important in the formation of the primary enamel knot.

First row - normal tooth development shown.
Bud stage the two factors shown then form BMP4. This proteins then form and diffuse and this causes the change from bud to cap stage.
Second row - no Msx1 so no BMP4 and tooth development stops at the bud stage. The mesenchyme signalling back to the epithelium is the most important stage in tooth development continuing.

Question 23

What genes are present at the bud stage?

Answer 23

Msx1, Pax9 and Shh at the bud stage.

The BMP4 activated the enamel knot which is then important in the bud stage.

Question 24

What is a transcription factor?

Answer 24

A protein that binds to DNA and controls transcription of the genes

Question 25

Cite two transcription factors playing a key role in the formation of the human dentition

Answer 25

PAX9 and MXS1

Question 26

At which stage of tooth development is set up the odontogenic homeobox code?

Answer 26

Initiation stage

Question 27

What type of molecule if Bmp4?

Answer 27

A growth factor (a protein).

Question 28

Where is Bmp4 expressed before tooth initiation?

Answer 28

Distally in epithelium

Question 29

At what tooth stage is set up the primary enamel knot?

Answer 29

Bud stage

Question 30

At what tooth stage does the PEK become active?

Answer 30

Cap stage

Question 31

Cite two mouse mutants in which the PEK does not form?

Answer 31

MSX1 and PAX1

Question 32

Does the mouse model faithfully reproduce the dental phenotype of humans carrying Msx1 mutations?

Answer 32

No as in the mouse, all the teeth are resting in the bud stage,

Question 33

Where is Shh expressed at the cap sage of tooth development?

Answer 33

Primary enamel knot