L7 - Ventralisation of the Neural Tube Flashcards
What is the single cell thick neural plate also referred to as
Neuroepithelium
When the neural tube forms what occurs to the medial lateral axis
Becomes the DV axis
Notochord is _______ to the neural tube
Ventral
Skin ectoderm is _______ to the neural tube
Dorsal
Neurones develop with ______________ throughout the entire DV axis
Bilateral symmetry
How can it be tested that the notochord acts as a DV axis organiser
Graft the notochord into an ectopic site
What occured when the notochord was grafted into an ectopic location
Induction of a secondary floor plate with bilateral symmetry of secondary motor neurones
What is the Shh homologue in drosophila
Hh
What does an insitu hybridisation against Shh show
That initially expressed in the notochord
Induced expression of Shh in the floor plate cells
What does an antibody stain show about Shh expression
Forms a gradient - highest ventrally and lowest dorsally
What does Shh confer
Ventral neural tube identities so progenitors will ultimately give rise to cells that differentiate into ventral motor neurones
What occurs when a bead soaked in Shh is grafted into an ectopic site
Mimics the effect of the notochord and floor plate
Induces the secondary floor plate and ventral motor neurones
What does Shh cause
Set of transcription factors which are a read outs of the Shh gradient
Where is the Shh gradient highest
Ventrally
What occurs as the ventral cells differentiate
The move laterally and differentiate into a neurone
Shh acts at an ___________ to confer a _______ pattern of TFs on progenitor cells
Early stage DV
Oncee the single cell neuroepithelium has been formed what is then induced
The neural tube
What does the mediallateral axis become
DV
Where does the notochord form
On the ventral surface
Whaere does the skin ectoderm form
On the dorsal surface
What is the floor plate closest to?
The notochord
The roof plate is ______ wherase the floor plate is ______
Dorsal
Ventral - next to the notochord
What occurs at the same time as the neuralation
The axial mesoderm (notochord and prechordal mesoderm) forms and comes just beneath the ventral midline of the neural tube
What do neurones develop with around the midline throughout the whole DV axis
Bilateral symmetry
What is secreted by the notochord and the floor plate cells
What does this act as
Shh
Morphogen
How can it be tested that the notochord and floorplate secrete a morphogen
What were the results of this experiement?
Grafting the notochord into an ectopic site into a host embryo
Induces a secondary floor plate and second set of motor neurones around - these exhibit bilateral symmetry
What does an in-situ hybiridisation over time for Shh show
Initially expressed in the notochord
This is then induced in the floor plate cells
What experiment could be used to show that Shh is acting as a morphogen
Antibody stain
What does an antibody stain for Shh show
Forms a concentration gradient (highest ventrally - lowest dorsally)
What does Shh cause
Expression of a certain set of TFs in the cells that it act on
What dose the TFs induced by Shh confer
Ventral neural tube identities so progenitors will give rise to cells that differentiate into ventral neurons
What is the experimental evidence that it is SHH as a signalling molecule
Bead soaked in purified Shh protein is able to mimic the effect of the notochord and floor plate - induces a secondary floor plate and motor neurones
In real life the set of TFs are readouts of the
Shh gradient
Shh is highest
Ventrally
What occurs to the cells as they differentitate
As they divide one cell retained as the mother cell and one moves laterally and differentiates into a neurone
Shh acts at an __________ to confer ________ of TF on progenitor cells
Shh acts an early stage to confer a DV pattern
What is the Shh gradient
Highest at the notochord and then the floor plate
What is the BMP graient
From neural plate border cells and then the roof plate cells
BMPs are members of the
TGF beta superfamily
Progenitor domains made up of bands of proliferating cells are established by …
The opposing action of BMPS/WNTS (dorsally) and Shh (ventrally)
Which way do cells move as they differentiate
Laterally
Descibe how hedgehog signalling occurs
Hh ligand binds to Ptc
Ptc then unable to inhibit Smo
Smo then causes an increase in the ammount of Gli activator
Hh signalling creates a balance of
Gli activator and repressor
What is the Hh signalling in the inactive form
No Hh ligand bound to Ptc
Normal function of Ptc is to inhibit Smo
Smo unable to cause increase in Gli activator
Smo unable to cause increase in Gli activator ]
More gli repressor than gli activators
Describe the phenotype of the Shh -/-
Multiple dysmorphology No ventralisation of neural tube Holoprosencephaly Cyclopia Abnormal limbs/digits Lack of pituitary
What is holoprosencephaly
Where there is no separation of the two parts of the brain
What does Shh govern
Governs ventralisation along the whole rosto-caudal axis
How come different neurones are formed at different levels along the A-P axis of the neural tube
The DV shh gradient intersects the AP hox gradient - forms a Cartesian grid of information - leads to different types of neurones being formed that are in the same DV position but differ on the AP axis
What type of neurones form in the forebrain
Hypothalamic neurones
What type of neurones form in the midbrain
Dopaminegric neurones
What type of neurones form in the hindbrain
Serotonergic neurones
What neurones form elsewhere along the DV axis
Motor neurones
