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BMS 249 - Developmental Neurobiology > Neural Crest and the formation of the PNS > Flashcards

Neural Crest and the formation of the PNS Flashcards

1
Q

Where are BMPs restricted to and why?

A

The region around the neural plate, as the BMPs in the neural plate are antagonised by BMPs from the node/organiser

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2
Q

What is the ‘neural plate border’?

What does it contain?

A
  • The border between cells which have BMP signalling and cells that don’t
  • Contains a mixture of cells between neural plate and ectoderm
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3
Q

What 3 things is the neural plate border crucial for?

A

1) Neural crest formation
2) Roof plate formation
3) Closure of the neural tube - the final step in neurulation

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4
Q

Where does the PNS derive from?

A

The neural crest

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5
Q

What is the roof plate involved in?

A

The patterning of dorsal fates of the neural tube

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6
Q

What is the first step of neural crest formation?

A
  • 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
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7
Q

When is Msx1 thought to be upregulated?

A

In response to intermediate BMP signalling

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8
Q

What is the 2nd step of neural crest formation?

A
  • 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
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9
Q

What is the 3rd step of neural crest formation?

A
  • Neural plate border TF (pax3, Zic1) act with Wnt to upregulate other Tfs (c-Myc, Id, snail, Sox9)
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10
Q

What is the 4th step of neural crest formation?

A
  • 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
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11
Q

What are the intrinsic TFs involved in neural crest cell formation?

A

Pax 3
Zic1
Pax 7

Sox 9
Snail
Id
c-Myc

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12
Q

What are the extrinsic TFs involved in neural crest cell formation?

A

Wnt

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13
Q

What does c-Myc upregulate and what does this do?

A
  • Upregulates Id

- Promotes cell proliferation and multipotnecy

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14
Q

What does Sox9 upregulate and what does this do?

A
  • Upregulates snail

- Prevents cell death

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15
Q

When does the neural tube close and what does this mark?

A

Once the neural crest cells have migrated away

Marks the end of neurulation

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16
Q

What do neural crest cells give rise to?

A
  • PNS: SNS, PNS, schwann cells, neuroglial cells etc
  • Adrenal medulla
  • Melanocytes (pigment cells)
  • DRG neurons
  • Facial cartiladge
  • Dentine of teeth
  • Enteric NS
17
Q

What determines the cell type formed by the neural crest?

A

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

18
Q

What are the main migratory pathways of neural crest cells and what do these give rise to?

A

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

19
Q

What are DRG?

A

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

20
Q

What are somites?

A

Blocks of mesoderm either side of the neural tube an notochord during development

Give rise to muscle, dermis and spinal column

21
Q

How do the neural crest cells which migrate through the somites form the DRG?

A
  • 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
22
Q

What explains the pattern of DRG along to axis?

A
  • Pissofffin forcing NCC to the anterior part of the somite
23
Q

What causes NCCs to differentiate and restrict their fate?

A

Signals they encounter when they are migrating

24
Q

What are roof plate cells?

A

Neural plate border cells which remain at the border and allow the 2 sides of the neural tube to fuse

25
Q

Where do roof plate cells occupy when the neural tube is closed?

A

The dorsal most region of the closed neural tube

26
Q

What are roof plate cells important in?

A

1) Final closure of the neural tube

2) Dorsal neural tube patterning

27
Q

How do roof plate cells help in the final closure of the neural tube?

A

The cells adhere together

28
Q

What do the roof plate cells transcriptionally upregulate when the neural tube is formed?

A

Secreted protiens BMPs and Wnts

29
Q

What do the roof plate cells do in the closed neural tube?

A

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
30
Q

How do the cells next to the roof plate respond to BMP and Wnt signalling?

What does this cause?

A
  • Upregulating a set of TFs (Pax6, Pax7, Pax3, Lim1)

- Causes the neural tube progenitors to acquire neural identities

31
Q

How does BMP from the roof plate act?

How is this different to what was previously thought?

A
  • 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
32
Q

How is BMP expression in the roof plate induced?

A

By BMPs which derive from the surface ectoderm, which grows over the developing neural tube

33
Q

Why do different dorsal cells acquire different neural identities?

A
  • 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
34
Q

What are progenitors?

A

Dividing cells (neural stem cells)

35
Q

What do specific progenitors give rise to?

A

Specific class of neurons

36
Q

What are progenitor subsets?

A

Blocks of cells which are each delineated through the expression of different transcription factors

37
Q

What properties do c-Myc and snail have?

A

‘stem-like’ behaviours, c-Myc is one of the first oncogenes to be discovered

38
Q

What partly determines the position of origin of the neural crest cells?

A

Hox genes

39
Q

How do Gli R and Gli A interact?

A

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

BMS 249 - Developmental Neurobiology (16 decks)

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