Dorsalisation

Question 1

Describe the neural tube folding

Answer 1

1. neural plate curves
2. neural plate border cells on each side are brought together and fuse
3. non-neural ectoderm grows over so the neural tube is internal

Question 2

Which transcription factors characterise neural plate border cells?

Answer 2

Pax3
Zic1
Pax7

Question 3

c-myc

Answer 3

oncogene

promotes cell proliferation

Question 4

Id

Answer 4

gives stem-like profile and pluripotency

Question 5

Snail

Answer 5

enables epithelial to mesenchymal transition

Question 6

How does the neural crest form?

Answer 6

1. Border cells at the interface between non-neural ectoderm and the neural plate receive intermediate levels of BMP signalling (mixture BMP signalling from non-neural ectoderm and BMP antagonists from organiser)
2. Induces expression of Msx1
3. Wnts, FGFs and Msx1 turns on neural plate border cell TFs = Pax3, Zic1 and Pax7
4. neural plate border cell TFs upregulate c-myc, Id, Snail and Sox9
   - promotes proliferation. multipotency, delamination, migration and survival
5. neural plate border cells upregulate TFs promoting epithelial-to-mesenchymal transition
6. neural crest cells delaminate from the border region and migrate away from the neural tube

Question 7

What are the cell types generated by neural crest cells determined by?

Answer 7

• original position of NCC along AP axis
• time of NCC generation
• migratory pathway of NCCs and the signals they encounter

Question 8

Superficial migratory pathway

Answer 8

NCCs migrating directly below ectoderm —–> melanocytes

Question 9

Intermediate migratory pathway

Answer 9

• NCCs migrate from the top of the neural groove into the anterior and posterior regions of somites.
• NCCs migrating into the posterior somite encounter pissoffin - forces NCCs into anterior somite
• NCCs coalesce —> dorsal root sensory ganglia

Question 10

What are bipolar neurons?

Answer 10

Neurons that project one axon into the spinal cord and project another axon into the periphery

Question 11

What do NCCs migrating between the somites and neural tube to reach the area underneath notochord become?

Answer 11

Parasympathetic or sympathetic ganglia

Question 12

What do NCCs migrating between the somites and neural tube to reach the area below the aorta become?

Answer 12

Adrenal medulla

Question 13

How do roof plate cells establish dorsal neural tube patterning?

Answer 13

1. roof plate cells secrete BMPs and Wnts
2. BMPs and Wnts diffuse into the dorsal neural tube
3. BMPs and Wnts activate BMP and Wnt signalling non-autonomously
4. Induces expression of Pax6, Pax7, Pax3, Lim1 = causes acquisition of dorsal neural tube identity
   Different BMPs turns on particular sets of TFs, which induces particular dorsal cell types

Question 14

evidence that BMPs are involved in dorsal progenitor formation?

Answer 14

• KO GDF7 (TGFb ligand) —-> D1A neurons lost, no loss of D1B neurons
• express diptheria toxin by knocking into GDF7 loci —> initial differentiation unaffected. then roof plate removed –> lose Math1 and Ngn1 expression. mash1 expression spreads dorsally.

Question 15

evidence that WNTs are involved in dorsal progenitor formation?

Answer 15

overexpress wnt - dorsal gene expression expands ventrally

reduce wnt - ventral genes expressed more dorsally

Question 16

what are neurons defined by?

Answer 16

• type of neurotransmitters produced
• channels
• receptors
• migratory patterns

Question 17

dlLB neuron

Answer 17

excitatory interneuron settling in dorsal horn

Question 18

how are different neurotransmitter phenotypes set up in dILA inhibitory interneurons?

Answer 18

only pax2 maintained?
> Pax2 -> NeuroD1/2/6 -> galanin & dynorphin
pax2 and lhx1/5 maintained?
> cooperatively turn on NPY & enkephalin

Question 19

cross-repression between which genes forms the boundary of dl4 and dl5?

Answer 19

• pax2

- tlx3