L9 - Neural Induction and Neural Tube Patterning

Question 1

What is the function of the organiser?

Answer 1

Neural inducing

Mesoderm dorsalisation properties

Question 2

Where is the organiser induced?

Answer 2

The organiser is induced mesoderm that lies directly above the Nieuwkoop centre

Question 3

During neural induction in the organiser what do ectoderm cells do?

Answer 3

Make and secrete BMPs
Diffuse out and act locally, binding to BMP receptors on adjacent cells
Trigger the BMP signalling pathway
BMP signaling pathway active - differentiation into epidermal ectoderm

Question 4

During neural induction in the organiser what do organiser cells do?

Answer 4

Intrinsically expresses secreted products (under influence of siamois and gsc)
Antagonists of BMP or components of BMP signalling pathway
- Chordin and noggin
Diffuse into extracellular space and compete for binding to BMPs in adjacent ectoderm cells
BMPs no longer able to activate their receptors
BMP signaling pathway not active – differentiation into neural

Question 5

What else do BMP antagonists act on?

Answer 5

Act on rest of non-organiser mesoderm to refine mesodermal fates

Question 6

Where do organiser derived signals diffue?

Answer 6

Diffuse through ventral mesoderm and pattern it

Diffuse locally into the ectoderm, resulting in the induction of neural tissue in part of ectoderm

Question 7

Low levels of nodal produces?

Answer 7

Ventral mesoderm

Question 8

High levels of nodal produces?

Answer 8

Organiser

Question 9

What experiment was carried out to prove neural induction by the organiser?

Answer 9

1920 - organiser graft experiment
Spemann and Mangold
Grafted an organiser from a donor to a host newt

Question 10

What were the results of the organiser graft experiment?

Answer 10

Another embryo developed whose secondary axis was host-derived
Neural tissue is induced from ectoderm, in response to signals from organiser tissue

Question 11

What is induction?

Answer 11

Example of a change in fate mediated by an extrinsic/ non-autonomous event

• Cell A makes a signal that acts on neighbouring Cell B
• Cell B is induced to become Cell C

Question 12

What is autonomous/cell-intrinsic differentiation?

Answer 12

Cell A divides asymmetrically

• One daughter has same fate as mother
• Second daughter inherits different components and cell-autonomously differentiates to alternate Cell fate X

Question 13

As the A-P axis begins to form what has already formed?

Answer 13

Neural tissue has already begun to form

Question 14

What starts the formation of the A-P axis?

Answer 14

Organiser autonomously differentiates and undergoes convergent extension – gastrulation

• As it does so, it self-differentiates into
  
  • Anterior endoderm - anterior
  • Prechordal mesoderm – anterior
  • Notochord – posterior
• Axial mesendoderm collectively

Question 15

What does development of axial mesendoderm drive?

Answer 15

Drives elongation and transition from neural plate to neural tube

Question 16

Gastrulation method

Answer 16

1. Organiser cells try to coalesce and form a rod
2. Rod migrates inside the cells of the animal hemisphere
3. First cells to migrate in - prechordal mesoderm cells
   - Mark future anterior endoderm
4. Last cells to migrate in - notochord cells
   - Underlie most of the body and mark future posterior end
5. Neural plate grows and elongates along A/P axis

Question 17

At the end of gastrulation..?

Answer 17

The rest of the body is built around the notochord cells/rod of mesoderm cells
Axial mesendoderm now underlies the midline of induced neural plate/prospective neural tissue

Question 18

What is the activation transformation model?

Answer 18

The basis for formation of forebrain versus hindbrain and spinal cord
Helps explain how the neural plate elongates

Question 19

How does the neural plate elongate?

Answer 19

Signals from notochord

• Cause cells at the back of the neural plate to proliferate
• Transform these cells from an anterior to a posterior identity
  
  • Represses anterior transcription factors
  • Promotes posterior transcription factors

Question 20

What signals are released by anterior tissues to establish early A-P regional identity?

Answer 20

BMP antagonists

Wnt antagonists

Question 21

What signals are released by posterior tissues to establish early A-P regional identity?

Answer 21

FGFs
Wnts
Retinoic acid

Question 22

Different domains of hindbrain and spinal cord are defined through?

Answer 22

Hox signature

Question 23

Retinoic acid gradient induces?

Answer 23

Different patterns of Hox transcription
As a result, different regions of the axis express different Hox genes
Important in rhombomeres of the hindbrain

Question 24

What does the interaction between hindbrain and forebrain cells produce?

Answer 24

Interaction induces midbrain cells at the boundary

Further events result in regionalisation of forebrain into diencephalon and telencephalon

Question 25

How is the D-V axis patterned?

Answer 25

After neuroepithelium is induced, it rolls up into the neural tube - Transforms medio-lateral axis into D-V axis Lateral edges fuse to become dorsal part of neural tube Neural tube pinches off from the overlying surface ectoderm

Question 26

Where are roof plate cells found?

Answer 26

Found in the most dorsal part of the neural tube - Induced in response to BMPS - They are neural plate border cells that have been retained

Question 27

What do roof plate cells upregulate?

Answer 27

BMPs | Wnts

Question 28

What do the signalling molecules released by roof plate cells do?

Answer 28

Diffuse into dorsal neural tube Induce expression of a set of transcription factors - Pax6, Pac7, Pax3, Lim1 - Induce dorsal identities in adjacent neural tube progenitors

Question 29

How many BMPs are expressed by the roof plate?

Answer 29

Many different BMPs expressed each of which induces a particular dorsal cell type

Question 30

What do BMPs and Wnts induce?

Answer 30

Induce different sets of progenitor cells - Through transcription factors - Will differentiate to distinct neuronal subsets in dorsal spinal cord

Question 31

What are the examples of cells that differentiate dorsally?

Answer 31

Roof plate cells Neural crest cells Dorsal sensory relay interneurons - D1-D3

Question 32

When is Shh released?

Answer 32

After BMPs have begun to pattern neural tube, the notochord upregulates Shh - Induces floor plate cells in ventral midline of neural tube - Floor plate also expresses Shh

Question 33

What is the role of Shh?

Answer 33

Acts as a morphogen | Induces floor plate cells

Question 34

What is the Shh gradient translated into?

Answer 34

Translated into an intrinsic GliA-GliR gradient in responding cells In turn, begin to express particular homeodomain transcription factors - These transcription factors are the upstream regulators of particular neuronal fate

Question 35

High Shh leads to?

Answer 35

High GliaA activity

Question 36

Low Shh leads to?

Answer 36

High GliaR activity

Question 37

As cells differentiate where do they move?

Answer 37

Laterally

Question 38

Overall what patterns the DV axis?

Answer 38

BMPs and Shh