L3 - Formation of Neural Plate

Question 1

Formation of neural precursors

Answer 1

Neural precursors first form at the surface

They develop next to the future skin on one side and next to mesoderm on the other side

Question 2

Homologous genes

Answer 2

Have different names in vertebrates and insects

• BMP7/Screw
• BMP1/Toll
• BMP4/DPP
• Chordin/SOG

Question 3

Chordin/SOG

Answer 3

Inhibit BMP signalling

Question 4

How does he neurogenic region arise overview

Answer 4

BMP/DPP signalling inhibited by antagonists
BMP and chordin are proteins encoded by genes conserved across evolution
The DPP/SOG network broadly dictates dorsal and ventral sides

Question 5

BMP/DPP signalling inhibited by antagonists

Answer 5

Chordin/SOG - act as sponges for BMP/DPP

Question 6

BMP and chordin are proteins encoded by genes conserved across evolution

Answer 6

BMP binds to receptor which leads to phosphorylation of SMAD
SMAD enters nucleus and acts within transcription factor complex

Question 7

DPP/SOG network broadly dictates dorsal and ventral sides

Answer 7

DPP – dorsal

SOG – ventral

Question 8

Evo-Devp

Answer 8

Suggests dorsal versus ventral nervous system
Developed as invertebrates underwent a body twist
So similarly, but reverse orientation, the neural plate forms where chordin inhibits BMPS

Question 9

Molecular pathway for development of neural plate cell

Answer 9

1. • BMP
2. Low Smad1 and high Smad7
3. Neutralising transcription factors
4. Neurogenin
5. NeuroD
6. Neural differentiation

Question 10

What is neurulation?

Answer 10

As vertebrate development progresses the neural plate rolls up to form the neural tube

Question 11

What is spina bifida?

Answer 11

Often have opening of the neural tube in the lower back

Question 12

In the Xenopus following fertilisation…

Answer 12

The egg undergoes mitotic cleavages and gives rise to hollow ball of cells
- 3 germ layers will form

Question 13

Mesoderm development in the Xenopus

Answer 13

Specialised type of mesodermal cell is induced – organiser
- Known as node in chicks and humans
It expresses special transcription factors and secreted ligands
Under the influence of transcription factors, the organiser expresses secreted products that are antagonists of BMP signal
- Chordin, Noggin, Follistation, Gsc

Question 14

Neural plate induction

Answer 14

It is induced in ectoderm where BMP is inhibited

BMP antagonists prevent the BMP ligand from stimulating its TGFβ receptors

Question 15

Differences between chick and human development

Answer 15

Flat not curved
Node secretes BMP antagonists which induce the neural plate
- Found in horse-shoe shape around node which extend downwards forming the neural plate
Node found at the end of the primitive streak
- BMP antagonists can be detected by in situ hybridisation with antisense probe

Question 16

What is gastrulation?

Answer 16

Development of axial mesendoderm (anterior endoderm/prechordal mesoderm/notochord) drives elongation and transition to neural tube
Cells in the organiser differentiate into anterior endoderm and axial mesoderm

Question 17

Invagination

Answer 17

Sheet of cells bends inwards

Question 18

Ingression

Answer 18

Individual cells leave epithelial sheet becoming free migrating mesenchyme cells

Question 19

Involution

Answer 19

An epithelial sheet rolls inward to form an underlying layer

Question 20

Epiboly

Answer 20

Sheet of cells spreads by thinning

Question 21

Intercalation

Answer 21

Rows of cells move between one another, creating longer but thinner sheet

Question 22

Convergent extension

Answer 22

Rows of cells intercalate but the intercalation is highly directional

Question 23

During gastrulation the anterior end/prechordal mesoderm are in close contact with?

Answer 23

The pharynx and ventral forebrain

Question 24

Experimental proof for neural induction by organiser

Answer 24

Took organiser from donor newt and transplanted to opposite side on host newt
BMP antagonists from grafted region diffuse out and induce to a neural identity
Leads to development of a second neural tube

Question 25

Discovery of BMP antagonists

Answer 25

1. Extract all mRNA from organiser cells
2. Reverse transcribe to cDNA
3. Test each to look for gene/protein that mimics organisers ability to induce secondary neural plate

Question 26

Features of neural inducers in organiser

Answer 26

Must be expressed in organiser
Must be secreted and act on adjacent cells
Overexpression in an ectopic site should lead to induction of secondary axis
Inhibition of activity should prevent axis formation
- Knock out
- Injection of dominant negative effector of signalling pathway
Show BMP antagonism is necessary for neural induction