L9 - Neural Induction and Neural Tube Patterning Flashcards
What is the function of the organiser?
Neural inducing
Mesoderm dorsalisation properties
Where is the organiser induced?
The organiser is induced mesoderm that lies directly above the Nieuwkoop centre
During neural induction in the organiser what do ectoderm cells do?
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
During neural induction in the organiser what do organiser cells do?
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
What else do BMP antagonists act on?
Act on rest of non-organiser mesoderm to refine mesodermal fates
Where do organiser derived signals diffue?
Diffuse through ventral mesoderm and pattern it
Diffuse locally into the ectoderm, resulting in the induction of neural tissue in part of ectoderm
Low levels of nodal produces?
Ventral mesoderm
High levels of nodal produces?
Organiser
What experiment was carried out to prove neural induction by the organiser?
1920 - organiser graft experiment
Spemann and Mangold
Grafted an organiser from a donor to a host newt
What were the results of the organiser graft experiment?
Another embryo developed whose secondary axis was host-derived
Neural tissue is induced from ectoderm, in response to signals from organiser tissue
What is induction?
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
What is autonomous/cell-intrinsic differentiation?
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
As the A-P axis begins to form what has already formed?
Neural tissue has already begun to form
What starts the formation of the A-P axis?
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
What does development of axial mesendoderm drive?
Drives elongation and transition from neural plate to neural tube
Gastrulation method
- Organiser cells try to coalesce and form a rod
- Rod migrates inside the cells of the animal hemisphere
- First cells to migrate in - prechordal mesoderm cells
- Mark future anterior endoderm - Last cells to migrate in - notochord cells
- Underlie most of the body and mark future posterior end - Neural plate grows and elongates along A/P axis
At the end of gastrulation..?
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
What is the activation transformation model?
The basis for formation of forebrain versus hindbrain and spinal cord
Helps explain how the neural plate elongates
How does the neural plate elongate?
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
What signals are released by anterior tissues to establish early A-P regional identity?
BMP antagonists
Wnt antagonists
What signals are released by posterior tissues to establish early A-P regional identity?
FGFs
Wnts
Retinoic acid
Different domains of hindbrain and spinal cord are defined through?
Hox signature
Retinoic acid gradient induces?
Different patterns of Hox transcription
As a result, different regions of the axis express different Hox genes
Important in rhombomeres of the hindbrain
What does the interaction between hindbrain and forebrain cells produce?
Interaction induces midbrain cells at the boundary
Further events result in regionalisation of forebrain into diencephalon and telencephalon
How is the D-V axis patterned?
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
Where are roof plate cells found?
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
What do roof plate cells upregulate?
BMPs
Wnts
What do the signalling molecules released by roof plate cells do?
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
How many BMPs are expressed by the roof plate?
Many different BMPs expressed each of which induces a particular dorsal cell type
What do BMPs and Wnts induce?
Induce different sets of progenitor cells
- Through transcription factors
- Will differentiate to distinct neuronal subsets in dorsal spinal cord
What are the examples of cells that differentiate dorsally?
Roof plate cells
Neural crest cells
Dorsal sensory relay interneurons - D1-D3
When is Shh released?
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
What is the role of Shh?
Acts as a morphogen
Induces floor plate cells
What is the Shh gradient translated into?
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
High Shh leads to?
High GliaA activity
Low Shh leads to?
High GliaR activity
As cells differentiate where do they move?
Laterally
Overall what patterns the DV axis?
BMPs and Shh
