VENTRALISATION Flashcards
At the same time as neurulation, convergent extension of the differentiated Node occurs and it comes to sit below the midline of the neural tube. The notochord before to upregulate transcription factors that induce cells at the ventral midline to become floor plate cells. What is this factor?
Shh
Shh signalling induced expression of transcription factors in progenitor cells that will confer what?
Ventral neural tube identity.
How can we test that ventral identity comes from the notochord and floor plate?
Test by grafting a donor notochord or floorplate to and ectopic position in a host embryo.
The ectopic notochord will induce a new floorplate and ventral neurons will form.
How was Shh identified?
Shh was first found in Drosophila.
Researchers identified mutations in a gene that cause a fruit fly to develop abnormally. The fruit flies look curled up and spiky leading to the name hedgehog.
In the 1980s, it was realised that Shh is conserved between invertebrates and vertebrates.
Shh mRNA is expressed in the notochord and then in the floor plate.
Where is Shh found?
When an antibody is made against the Shh protein, it is shown to diffuse away from the notochord and floorplate forming a concentration gradient in the ventral part of teh nerual tube.
How can it be shown that Shh is the induced factor that gives rise to ventral identity.
Ectopic floor plate and ventral neurons induced after implantation of Shh soaked bead.
There is a large concentration going from ventral to dorsal of Shh, what happens?
Discrete transcription factors are induced as a result of specific concentrations of Shh along the DV axis.
As cells are differentiating in the neural tube, what is also happening.
They are moving laterally.
A band of progenitors will remain as the adult stem cell niche of the spinal cord.
If a progenitor cell, guided by Shh, upregulates Nkx6.1 and Olig2, what will it give rise to?
A differentiated motor neuron.
What is the other function of Shh?
Shh patterns early neuroepithelial progenitor cells. Specific subtypes of differentiated neurons will arise, each born in a distinct and predictable zone alon gthe DV axis of the nerual tube.
Eg Motor neurons form ventrally under the influence of Shh
Interneurons form dorsally under the influence of BMPs and sensory neurons come from the neural crest cells.
Neural development does not stop after differentiation. After a neuron has differentiated, what occurs?
The neuron will begin to project axons which follow pathways to target cells.
Describe the Shh pathway.
The activity of Smoothened, a transmembrane protein, is suppressed by the Shh receptor, Patched, when there is no Shh. Under these circumstances, the Gli transcription factors are present in the repressive form.
If Shh binds to Patched thereby activating Smoothened, the Gli transcription factors can be shifted to their activator forms resulting in transcription of Shh target genes.
What happens if you make an Shh-/-?
The entirety of the body along the AP axis will have no vertalisation.
- No ventral neural tube
- Cyclopia
- Holoprosencephaly
- Lack of pituitary
- Abnormal limbs
- Often born with a proboscis
Shh coming from the ventral cell groups intersects with the earlier established A-P domain of the neural tube. What effect does this have?
Effectively creates a cartesian grid of information. Cells respond by changing fate in accordance to where they lie in the grid due to their competency to respond to Shh based on the different transcription factors they are already expressing. Hence, different types of neurons differentiate at the same D-V position along different parts of the A-P axis.
What kinds of neurons does Shh induce in the brain?
Hypolathamic neurons in the forebrain.
Dopaminergic neurons in the midbrain.
Serotonergic neurons in the hindbrains.
Motor neurons elsewhere - mainly spinal cord.
