Neuro and Gliogenesis Flashcards
(42 cards)
1
Q
What cells make up the neural tube?
(2 marks)
A
- Neuroepithelium
- A pseudostratified epithelium - every cell contacts basal lamina
- Allows you to pack more cells in a small space
2
Q
What does the neural tube give rise to?
(5 marks)
A
- Cerebellum:
- some progenitals migrate to outer most part of external granula layer and start producing neurons there and then move down to:
- Ventricular zone
- Mantle zone
- Internal granular zone
- Purkinje layer
- Marginal zone (neurons made)
- some progenitals migrate to outer most part of external granula layer and start producing neurons there and then move down to:
- Cortex:
- Neurons organised into 5 different layers: v. zone, sub v zone, mantle zone, cortical plate, marginal zone
3
Q
What happens to the embryonic complex during development?
A
Increases in size and complexity
4
Q
What does this image show?
A
- histone HC that’s been stained and is present in cells undergoing mitosis ⇒ present in lining of ventricle
5
Q
What do progenitor cells do at the ventricular zone?
(4 marks)
A
- Progenitors come down and divide at ventricular surface and then move up again
- Progenitor in S phase, nucleus is at top of ventricular zone
- Once finish replicating DNA at G2 phase they come down - by time they go into mitosis at ventricle
- After 2 cells seperated and G1 phase starts again - cells move back up towards marginal zone
6
Q
What mediates interkinetic nuclear migration?
(5 marks)
A
- Microtubule dual motors
- Proteins that carry nucleus up and down
- KIF1A - essential for basally directed nuclear migration in radial glial progenitor cells
- Dynein - nuclei travel much faster in basal direction with dynactin
- Need to move nucleus up and down as don’t have space to have them all dividing at same time
7
Q
Apart from lack of space, what is another hypothesis suggested for the reason progenitor cells are moved up and down the cortex?
(3 marks)
A
- Moving nucleus up and down may expose it to different environments of signalling molecules
- MAY inform cell if it needs to proliferate, make neurons
- Movement also dependent on cell cycle progression
8
Q
What are the main progenitor cells in rodents?
A
Radial glial cells and Intermediate progenitor cells
9
Q
Explain what radial glial cells are including divisions, migration etc.
(6 marks)
A
- Apical progenitors and move up and down
- Positive for Pax6
- Symmetric and asymmetric division
- Polarised
- Contracts ventricular and pial surface - top of brain
- Cell bodies in ventricular zone (area where nuclei and migration happens)
10
Q
Exlpain what intemediate progenitor cells are: ,igration, divisions etc.
(5 marks)
A
- Basal progenitors
- Tbr2 positive
- Symmetric divisions
- Multipolar cells
- No contact with apical or pial surface
11
Q
Where are progenitors located?
A
Sub ventricular zone
12
Q
How can you trace neurogenesis using a viral injection?
(4 marks)
A
- Inject pregnant mouse with retroviruses that express GFP into ventricle of embryos
- Retroviruses infect cells that are dividing (progenitors)
- Dividing cells are at ventricle - one of them gets infected with retroviruses and will integrate in genome
- All progeny infected and part will be colour shown and labelled
13
Q
What was revelead from the experiment of a viral injection into mice?
A
RGC are progenitor cells and generate neurons and intermediate progenitors
14
Q
What are the different types of ways neurons can be generated?
(2 marks)
A
- RGCs can directly produced neuron through asymmetric mitosis - gives another progenitor and a neuron
OR
- RGC divides indirectly and form another RGC and IPC - this then divides and produce 2 neurons
- (two forms of division in the second one)
15
Q
What is the upper layer hypothesis?
(3 marks)
A
- RGC make neurons for layers 5 and 6
- IPC make neurons for layers 2,3,4
Based on expression of markers Ngn1/2 and Otx2 which are found in v zone in neurogenesis and later in deep layers in cortex
16
Q
What experiment disproved the upper layer neuron hypothesis?
(6 marks)
A
- Used pre-recombinase to trace progeny of intermediate progenitors
- Get reporter mouse line (Aid 9-td Tomato) - and give Cre
- cells will recombine particular LoxP sire in DNA and express fluorescent protein
- Tbr2 is marker for IPC:
- Take this Tbr2 line and mate with Aid9-td Tomato: every IPC that turns on Tbr will turn on Cre
- Cells become red and can see where they end up therefore not ture that all upper layer neurons are from divisions of RGC
17
Q
What is a birthdating exepriment?
(3 marks)
A
- Used to see when cells are born using radioactive bases or base analogues
- Inject animals with 3H-thymidine at E11 - gets used up so doesn’t stay long
- Only neurons made at E11 will be labelled
18
Q
Why is 3 H-thymidine being switched out for Brdu more recently?
A
Brdu used much less complicated detection antibody and immunofluorescence
19
Q
What do birthdating experiments reveal about the formation of the cortex?
(4 marks)
A
- Cortex built from inside out pattern
- In neurogenesis 1st projection neurons born are ones that go to deepest layer
- Maker layer 6 1st then 5,4 etc.
- Every layer of neurons generates has to go all the way to the top
20
Q
What happens after neural stem cells proliferate? Why do they do this and what are the cascade of events that follow?
(3 marks)
A
In order to make necessary neurons
Then there’s a switch from porliferative stage to neurogenic
When neurons are finished being made, glial cells are produced in the cortex, then once neurogenesis stops, get production of atrocytes
21
Q
What happens from neuro to gliogenesis at:
E8
E12
E17
A
- E8:
- neural tube lined with neuroepitheliual cells undergoing to symmetric proliferation
- Neuroepithelial cells transition to raidal glial cells and also divide in symmetric proliferative
- E12:
- Mode of division changes to asymmetric neurogenic divisions
- Radial glial cell drive to produce 2 different daughter cells
- E17/18:
- Switch in division but asymmetric neurogenesis divisions will continue
- Switch from producing RG cells will undego symmetric division where they deplete themselves and only produce astrocytes and oliodendrocyte precursor cell
22
Q
What happens if neurons are produced too early?
A
Deplete progeitor pool and won’t have enough progenitors to generate all neurons for the layers
23
Q
What happens if neurons are produced too late?
A
May have missed neurons you were meant to generate or create too many
24
Q
What is the basis of symmetric division?
(3 marks)
A
- Early on and also self renewal division
- E.g. RGCs can produce 2 daughter cells = progenitors
- In some organisms division angles play a role e.g. drosophila
25
What is the basis for asymmetric division?
(2 marks)
* Fate of 2 daughter cells that **aren't identical**
* Normally happens in neurogenic division
26
How is everything divided in symmetric division?
(4 marks)
* EVERYTHING in parent cell is **split equally**
* Part of _progenitor touches ventricle_ (key domain for cells) - progenitor **gives it polarity** and keeps them as progenitors
* Centrosomes have to replicate when cell does so always have **mother and daughter centrosome**
* Daughter cells of RG get either mother or daughter centrosome
27
How is everything divided in asymmetric division?
(2 marks)
* Terminals are not split equally
* One cell gets higher amount of proteins that will lead to it becoming something different
28
As neurogenesis progresses, what happens to the cell cycle? How can this be seen embryonically?
(2 marks)
* Cell cycle length **increases**
* Progenitor at **E12** takes a **shorter time to divide** than the one at E14 and 16
THIS CREATES A BALANCE BETWEEN SELF RENEWAL AND NEUROGENESIS
29
What happens if you get either:
proliferative
asymmetric
symmetric
division in G1 phase?
(7 marks)
* _Proliferative:_
* More protein but **divide early** so *_no differentiation_*
* _Differential asymmetric division:_
* Cell has gone just past threshold, **each daughter cell has different fate**
* _Differential symmetrical division:_
* cell cycle is very long in neurogenesis
* doesn't matter what time it is at, as long as cell divides to produce **same daughter cells**
30
How does Notch signalling affect the formation of a neuron?
(4 marks)
* **Expressed on surface** of progenitor cells
* notch binds to **ligand DU1** on neuron cell
* Receptor is processed - its intracellualr domain released and goes inot nucleus which triggers expression of Hes1 and Hes5
* ^^ are TF which inhibit production of pro-neural TF therefore **_more notch_** on surface you're **_less likely_** for cell to become neuron
31
What was the experiment carried out to see how intrinsic mechanisms influence what progenitors do?
(4 marks)
* Take progneitor cell from an animal at a particular age and transplant it into an older animal
* Found is progenitor has gone through **S phase** then in the older animal it will continue to **make layer 6 neurons**
* Whereas take same progenitor cell **before its completed S phase** and **transplant it** to older animal, will produce whatever neurons are specific to that time period
32
What does Notch signalling promote?
| (2 marks)
* At early neurogenesis **promotes maintenance of neural stem**, cell fate
* Later on **promotes gliogenesis**as signalling happens in different trancriptional environment
33
What happens first neurogenesis or gliogenesis?
Neurogenesis happens first and gliogenesis starts AFTER neurogenesis has finished
34
What happens to the Jak/Stat pathway to induce gliogenesis?
(4 marks)
* There's an increase in Jak/Stat pathway which *_tips balance to producing glial cells_* due to:
* Demethylation of promoters caused by Nothc signalling
* Decrease in Ngn1 and Ngn2
* Increase in Ct-1 secreted by young neurons)
35
How does Notch signalling promote gliogenesis?
(5 marks)
* At end of neurogenesis, **Notch activates nuclear factor 1A which promotes gliogenesis**
* Further poteniates _Jak/Stat_ signalling pathway through _Hes genes_ and _demethylation of GFAP promoter_
* Shift in BMP signalling output:
* Get activation of genes that **promote glial fate** and deactivation of genes that promote neurogenesis
* Inhibition of proneural TFs
36
Where do the different waves of oliogdendrocyte production happen?
(3 marks)
1st wave: **ventral forebrain** and spinal cord - _dependent on Shh_
2nd and 3rd wave: progressively **more dorsal** - _independent of Shh_. RG cell produces OPC (oligo. precursor cell) - oligodendrocyte - proliferates in mammalian brain througout life
37
What is a gyrencephalic brain?
Denoting brains, such as that of humans, in which the **cerebral cortex has convolutions,** in contrast to the lissencephalic (smooth) brains of small mammals
38
What are the neural progenitor types present in a gryencephalic brain?
(6 marks)
* **Basal radial glial cells** that have lost contact with apical surface but maintain contact with basal lamina
* Basal radial glial cells can generate more than two of themselves in **outer subventricular zone** (actively divide)
* Apical radial glia
* Intermediate progenitor
* Subapical progenitor
* Transient basal radial glia
39
What is a rodents preferred pathway of generating neurons?
* RG gives rise to intermediate progenitors to make neurons
40
What is the preferred pathway of making neurons in primates?
* RG to BRG or IPC therefore there's a **much higher ratio** of neurons being produced basally than apically
41
What happens if you increase apical and basal mitosis?
(2 marks)
Get **moer elongated brain**if you don't allow tit to expand would have **gyrefied** both in apical and basal domains
If you shift hte balance get more neurons basaly than apically as don't have to increase ventricular zone and can generate a much higher surface
42
