Nervous system development Flashcards
What did Spemman and Mangold’s Organiser Experiment show?
That secreted signals can induce and pattern CNS development.
Give the 3 main steps in Spemman and Mangold’s Organiser Experiment.
- Remove dorsal blastopore lip from a donor
- Transplant into host on the opposite side (anterior)
- Will form a conjoined twin
Which organism was Spemman and Mangold’s Organiser Experiment first performed on?
Xenopus.
What is interesting about the conjoined twin formed in Spemman and Mangold’s Organiser Experiment? What does this show?
The majority of the conjoined twin is made of host tissue NOT donor tissue. Shows that the donor tissue has induced CNS formation in the host.
Give 4 examples of Organiser molecules.
- Chordin
- Noggin
- Follistatin
- Xnr3
What do the Organiser molecules all have in common?
They are antagonists of BMP signalling.
Where are the Organiser molecules found? Give 3 places.
- Dorsal endoderm
- Dorsal mesoderm
- Neural ectoderm
A combination of what 2 things causes neural induction in the ectoderm?
- Supression of BMP by antagonists
2. FGF signals
What is FGF signalling?
Fibroblast growth factor.
What 3 groups all promote posterior neural identity?
- Wnts
- Retinoic acid
- FGFs
The positive signals that promote posterior neural identity are known. What positive signals promote anterior neural identity?
No positive signals are known - anterior identity is established by protecting cells from caudalising agents
What is a caudalising agent?
One that is involved in the transformation of the posterior neural components.
Why does the embryo elongate in neurulation?
To move the anterior part away from caudalising agents.
To establish anterior neural identity which genes can be antagonised (inhibited)?
Wnt proteins
What happens to the anterior CNS if there is too much Wnt signalling?
It fails to form
What happens to the anterior CNS if there is not enough Wnt signalling?
It expands, not enough posterior CNS is established
How is the neural tube formed?
The neural plate rolls up on each side and fuses down the middle.
What happens to the neural crest cells as the neural tube is formed?
They delaminate and migrate away.
What is the notochord?
A solid rod of mesoderm down the dorsal side of the embryo which is important for tissue patterning.
Where do the motor neurones differentiate?
On the ventral side of the spinal chord.
What 3 events constitute as the dorsoventral patterning of the CNS?
- The formation of the neural tube
- The delamination of the neural crest cells
- The differentiation of the motor neurones
What is the neural floor plate?
A group of cells responsible for the differentiation of neurones and the ventralisation of tissues.
Where is the neural floor plate located?
On the ventral midline of the neural tube.
What happens if you transplant the developing notochord to a new location?
It will continue to produce neurones and floor plate cells.
In transplant experiments, in what proximity to the notochord are the floor plate cells it produces? What does this suggest?
Very close by, short-range signalling.
In transplant experiments, in what proximity to the notochord are the neurones it produces?
Further away than the induced floor plate cells.
What happens if the notochord is removed completely?
There are no neurones or floor plate cells produced.
What signal is secreted by the notochord?
SHH (sonic hedgehog signalling molecule).
What does SHH do?
Causes the ventral side of the neural tube to produce floor plate cells and other cell types.
What is the gradient of SHH across the neural tube?
High (ventral) to low (dorsal).
SHH could be regarded as a morphogen in neurulation. Why?
The concentration of SHH affects the cell types that are produced.
What do homeodomain proteins do?
Establish discrete dorso-ventral domains.
Where are homeodomain proteins located in regards to SHH?
Downstream.
There are 2 classes of homeodomain factors. These become expressed at different concentrations of SHH. What are they?
- Class I = low levels of SHH (ventral)
2. Class II = high levels of SHH (dorsal)
What are established by interactions between Class I and II homeodomain factors?
Mutually repressive boundaries.
Dbx2 is a gene expressed in low levels of SHH. What does it repress?
Nkx6, expressed in high SHH.
Pax6 is a gene expressed in low levels of SHH. What does it repress?
Nkx2, expressed in low SHH.
What accounts for the huge disparity in size between organisms?
Growth and proliferation rates.
Neural signalling is location dependent. What does this mean?
The same signalling molecules can produce different parts of the CNS based on location.
What does SHH do in the spinal cord and brain respectively?
- Promotes neuron development
2. Induces the hypothalamus and parts of the eye.
What happens if SHH is removed from the eye?
Cyclopia develops.
What 2 things coordinate differentiation of cells?
- Position along the DV axis
2. Position along the AV axis
What allows a single mother cell to form two different daughter cells. Give 2 factors.
- Polarised cell division
2. Asymmetric distribution of cytoplasmic determinants
Where does newly formed neural tissue (ectoderm) and mesoderm aggregate?
At the caudal (posterior) end of the embryo.
The caudal region of the embryo is divided into 3 parts. What are these?
- Differentiation zone
- Proliferating zone
- Zone at the very end where differentiated/proliferating cells move to.
In which region of the embryo is retinoic acid expressed?
Anteriorly.
In which region of the embryo is FGF expressed?
Caudally.
What happens at the interface of retinoic acid and FGF expression?
Neural cells switch on expression of genes that make neurons.
What does antagonising enzymes that degrade retinoic acid do?
RA helps to establish the anterior identity of the CNS.
What affect does FGF expression have on RA production?
Switches it off.
Once the nervous system has taken shape, the neurons migrate before fully differentiating. True or false?
True.
Give an example of neuronal migration.
Those in the ventral part of the forebrain migrate to the dorsal forebrain and into the cortex.
When are the axons of neurones generated?
After differentiation.
What causes axonal growth?
The growth cone.
What 3 factors guide axons to their target locations?
- Long-range repellents
- Long-range attractants
- Locally acting contact mediators
What must be established when axons reach their target destinations?
Appropriate synapses between the correct neurones.
Cell death is common in development. Why?
It kills off cells that are no longer needed.
Which kind of experiments show cell death in the CNS?
Extra limb experiments - if there is an extra limb that needs innervation, there is less cell death.
The majority of the CNS is morphologically symmetrical. In humans, where does asymmetry arise from?
There is a preference for ‘handedness’.
There are asymmetries in the brain of all animals. What is this indicative of?
Lateralisation of the CNS, i.e. different brain hemispheres specialise in different things.
Is left-right asymmetry easy to detect in zebrafish?
Yes.
