Neural Crest and the formation of the PNS Flashcards
Where are BMPs restricted to and why?
The region around the neural plate, as the BMPs in the neural plate are antagonised by BMPs from the node/organiser
What is the ‘neural plate border’?
What does it contain?
- The border between cells which have BMP signalling and cells that don’t
- Contains a mixture of cells between neural plate and ectoderm
What 3 things is the neural plate border crucial for?
1) Neural crest formation
2) Roof plate formation
3) Closure of the neural tube - the final step in neurulation
Where does the PNS derive from?
The neural crest
What is the roof plate involved in?
The patterning of dorsal fates of the neural tube
What is the first step of neural crest formation?
- Non-neural ectoderm expresses BMPs which act upon the outer edged of the neural plate
- Forming a border between the induced neural plate and the ectoderm (the neural plate border)
- Causes the upregulation of Msx1
When is Msx1 thought to be upregulated?
In response to intermediate BMP signalling
What is the 2nd step of neural crest formation?
- In cells that express Msx1, Wnt and FGFs are upregulated
- These act together with Msx1 to turn on other TFs (pax3, pax7, Zic1)
- All of these TF characterise the neural plate border cell
What is the 3rd step of neural crest formation?
- Neural plate border TF (pax3, Zic1) act with Wnt to upregulate other Tfs (c-Myc, Id, snail, Sox9)
What is the 4th step of neural crest formation?
- In responce to c-Myc and sox9, genes that control proliferation, multipotnecy and cell survival are upregulated
- At the same time, neural crest TF (snail) upregulate a further set of TF which promote ETM transition
- Neural crest cells delaminate as individual cells and begin to migrate away
What are the intrinsic TFs involved in neural crest cell formation?
Pax 3
Zic1
Pax 7
Sox 9
Snail
Id
c-Myc
What are the extrinsic TFs involved in neural crest cell formation?
Wnt
What does c-Myc upregulate and what does this do?
- Upregulates Id
- Promotes cell proliferation and multipotnecy
What does Sox9 upregulate and what does this do?
- Upregulates snail
- Prevents cell death
When does the neural tube close and what does this mark?
Once the neural crest cells have migrated away
Marks the end of neurulation
What do neural crest cells give rise to?
- PNS: SNS, PNS, schwann cells, neuroglial cells etc
- Adrenal medulla
- Melanocytes (pigment cells)
- DRG neurons
- Facial cartiladge
- Dentine of teeth
- Enteric NS
What determines the cell type formed by the neural crest?
1) Position of origin of the neural crest cells (along the AP axis)
2) Time of generation of the neural crest cells
3) Migratory pathway of the neural crest cells
- What signals they encounter en-route or at the target
What are the main migratory pathways of neural crest cells and what do these give rise to?
1) Through somites - coalesce and differentiate to give rise to DRG
- Differentiate further into bipolar neurons, with one axon to the spinal cord and one to the periphery
2) Between the somites and the neural tube
- When reach between the notochord and underlying aorta - coalesce and form the SYMPATHETIC or PARASYMPATHETIC GANGLIA
3) Below the aorta - form adrenal medullar
4) Over the top of the somites, into the skin - form melanocytes
What are DRG?
Dorsal root ganglion
Collection of cell bodies of the PNS, which axons enter the spinal cord and run along the dorsal side of the spinal cord
What are somites?
Blocks of mesoderm either side of the neural tube an notochord during development
Give rise to muscle, dermis and spinal column
How do the neural crest cells which migrate through the somites form the DRG?
- Migrate through anterior and posterior part of the somite
- At the posterior end, encounter PISSOFIN
- PISSOFIN forces NCC into the ANTERIOR part of the somite
What explains the pattern of DRG along to axis?
- Pissofffin forcing NCC to the anterior part of the somite
What causes NCCs to differentiate and restrict their fate?
Signals they encounter when they are migrating
What are roof plate cells?
Neural plate border cells which remain at the border and allow the 2 sides of the neural tube to fuse
Where do roof plate cells occupy when the neural tube is closed?
The dorsal most region of the closed neural tube
What are roof plate cells important in?
1) Final closure of the neural tube
2) Dorsal neural tube patterning
How do roof plate cells help in the final closure of the neural tube?
The cells adhere together
What do the roof plate cells transcriptionally upregulate when the neural tube is formed?
Secreted protiens BMPs and Wnts
What do the roof plate cells do in the closed neural tube?
Secreate BMP and Wnt mRNA to neghbouring cells, which act in a non-autonomous manner to REACTIVATE BMP and Wnt signalling neighbouring cells
- This upregulates sox2
How do the cells next to the roof plate respond to BMP and Wnt signalling?
What does this cause?
- Upregulating a set of TFs (Pax6, Pax7, Pax3, Lim1)
- Causes the neural tube progenitors to acquire neural identities
How does BMP from the roof plate act?
How is this different to what was previously thought?
- Roof plate cells express MANY types of BMPs, which each induce different types of dorsal cell
- Some BMPs diffuse futher than others
- Previously thought that BMP acted as a morphogen
How is BMP expression in the roof plate induced?
By BMPs which derive from the surface ectoderm, which grows over the developing neural tube
Why do different dorsal cells acquire different neural identities?
- They see different BMPs which turn on different subsets of TFs in the progenitor cells of the single cell layered epithelium
- These subsets of TFs determine what neuronal cell the progenitor will become in the adult body
What are progenitors?
Dividing cells (neural stem cells)
What do specific progenitors give rise to?
Specific class of neurons
What are progenitor subsets?
Blocks of cells which are each delineated through the expression of different transcription factors
What properties do c-Myc and snail have?
‘stem-like’ behaviours, c-Myc is one of the first oncogenes to be discovered
What partly determines the position of origin of the neural crest cells?
Hox genes
How do Gli R and Gli A interact?
They both sit on the promoter of the gene
Gli R masks the activation site - prevents Gli A from binding when no Hh is present
