Signalling pathways in tooth development Flashcards
How do we know that cells in the teeth communicate?
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.
Signals from where control tooth initiation?
Will these tissue combinations produce a tooth?
- Oral ectoderm and odontogenic mesenchyme 1st BA
- Isolation of the two above
- Oral ectoderm and non-odontogenic mesenchyme
- Non-oral ectoderm and odontogenic mesenchyme 1st BA
Oral ectoderm
- Yes
- No
- Yes
- No
Where is the information for communication between tooth tissue?
Where is the information for the specific tooth structure kept?
Oral ectoderm
Mesenchyme
Why do we go from a homeogenesis cell population to cells with different properties?
Teeth contain the same genetic information but express different genes.
What gene is expressed in the mesenchyme of a tooth?
Pax9.
What are the 3 ways these cell communicate?
- Diffusion
- Gap junction
- Direct contact
Give the four steps to communication via secreted molecules
- Production and release of secreted factors (signals)
- Diffusion of signals to the target
- Detection of the signal by a receptor on the target cell
- Change in gene expression/cell behaviour (shape/movement) in the target cell.
What are 4 common growth factors in teeth called?
- Sonic hedgehog
- Wnts
- FGFs (Fibroblast Growth Factor)
- BMPs (Bone morphogenetic Protein)
Signals are converted to responses in the cell in three stages…
- 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.
What is the outcome of secreted molecules?
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.
What two signals types happen between the epithelium and mesenchyme?
Sequential and reciprocal
Give three examples of when epithelial-mesenchymal cell interactions occur?
- Patterning of the dentition
- Tooth initiation
- Beginning of tooth morphogenesis
(in chronological order)
Gives two details on the homeodomain transcription factors
Prior to any morphological sign of tooth development.
Patterning of the dentition.
Information to form a tooth - contained in —-.
Tooth shape and type info is contained in —-.
Epithelium
Mesenchyme
When are mesenchymal signals established?
Prior to tooth development.
Molecules within the ectoderm will be secreted in different area.
What growth factor is secreted with molars and which with incisors with mesenchymal signals?
Where do these molecules diffuse?
Fibroblast growth factors with molars and bone morphogenetic protein with incisors.
These diffuse into underlying mesenchyme and bind there.
What part of the tooth in molars and incisors are the genes present?
Molars - outer edges of tooth
Incisors - centre of tooth
What happens to some transcription factors in the odontogenic homeobox code?
They overlap
Explain the shh signalling pathway
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.
What happens if there is no Shh signalling?
Arrest of tooth development
What do Wnt/Shh interactions control?
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.
Explain BMP signalling that occurs
Explain what happens with BMP and without it
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.
What genes are present at the bud stage?
Msx1, Pax9 and Shh at the bud stage.
The BMP4 activated the enamel knot which is then important in the bud stage.
What is a transcription factor?
A protein that binds to DNA and controls transcription of the genes
Cite two transcription factors playing a key role in the formation of the human dentition
PAX9 and MXS1
At which stage of tooth development is set up the odontogenic homeobox code?
Initiation stage
What type of molecule if Bmp4?
A growth factor (a protein).
Where is Bmp4 expressed before tooth initiation?
Distally in epithelium
At what tooth stage is set up the primary enamel knot?
Bud stage
At what tooth stage does the PEK become active?
Cap stage
Cite two mouse mutants in which the PEK does not form?
MSX1 and PAX1
Does the mouse model faithfully reproduce the dental phenotype of humans carrying Msx1 mutations?
No as in the mouse, all the teeth are resting in the bud stage,
Where is Shh expressed at the cap sage of tooth development?
Primary enamel knot
