Regeneration Flashcards
What are quiescent cells?
Cells which are in G0 and are activated by there is damage to the tissue. They will replace the tissue e.g. muscles when you go to the gym
What is the link between complexity of the organism and the ability to regenerate?
There is none. Some worms have incredible capacity to regenerate whilst C.elegans cannot at all
What are the two ways in which something can regenerate?
Morphallaxis-
Epimorphosis
What is Morphallaxis?
No change in cell number- repatterning of existing cells- they change their fate and positional values
What is Epimorphosis?
Growth zone which forms at the cut off and this initiates proliferation and thus regrowth
Example of typical morphallaxis?
Hydra- they continuously growth throughout their lives bu they stay the stay the same size- there must be regeneration
The way they do this is by changing cells positional values/fates
You can see this in fate mapping- cells identity and position will change throughout the life of the organism.
Growth is not required- treat them with GF inhibitors and they still regenerate
In Hydra, how does the head regenerate
In the head there are two gradients. 1 is the positional value- this determines head inducing ability (cells in the head are very good at inducing head). It also gives cells resistance to an inhibitor of head cells which is the second gradient
Experiments to show the gradients in Hydra head
To show the inhibitor- take hydra and take cells from just below the mouth region. Transplant lower down- no effect.
If you remove the head of the host you have removed the head inhibitor source. You will get an ectopic head because the cells no longer have the right signals to inhibit head growth.
Take the same section of tissue and transplant it at the bottom of the hydra- get an ectopic head because there is no inhibitory signal
How to show head inducing capacity
Take donor and remove head
Take section of tissue from headless hydra and transplant in same position as the first experiment- a head will now form. We think that cells have changed their positional values . The region of cells which you took the transplant from had become head like that their signals are now too strong to be overcome (look at slide photos it makes more sense)
What controls the head organiser?
Wnt/Bcatenin signalling.
When there was GSK3Beta inhibition- beta catenin nuclear concentration is increased and all regions acquire the fate and characteristics of the head organiser
Example of epimorphosis
tailed amphibians- can regenerate whole limbs and retinas.
If you dissect a limb- depending on the position of the cut all of the right structures will be regenerated
What is unusual about the retinal regeneration>
It is regenerated from the iris which is from a different germ layer
Where do the cells for epimorphosis come from?
Cells de-differentiate instead of using stem cell processes.
After amputation, there is epidermal cell migration which closes over the wound (essential- if this is stopped there is no regeneration)
Morphogen gradients in regeneration have to be large in the adult than in development because the scale is much larger
Are the developmental and regeneration processes the same?
Very slight differences-
Cells below the epithelium (epidermis which has covered the wound) will de-differentiate and form a blastema- cells which form this are derived from the dermis, cartilage and muscle.
What happens to muscle cells when they de-differentiate
The fact the muscle cells are involved is surprising because they are multinucleate.
They shatter and become mononucleate which is driven by Thrombin, Msx1 and pRb- cells re-enter the cell cycle
What is the blastema
Not a stem cell- there are limited transdifferentiation between the different cell types which make it up- they have factors from the cell type which they came from
Experiments around the blastema
GFP- took cells of known origin and saw what they became in the blastema and regenerated limb- differentiated back into the cell type which they came from apart from some crossover between dermis and cartilage
What are the rules of regeneration
Limb regeneration is always distal to the wound- you only form structures which have been removed
This is according to the positional value at the site of the cut- you’re not just replacing what is missing (cells cannot tell what is missing, only what they can make)
What is the molecular basis of regeneration
Thought it was through differential adhesion
Can be seen if you take blastemas from proximal and distal cuts and co-culture them- the proximal cells will engulf the distal cells- shows that two different cell types prefer to adhere to cells of the opposite type and not themselves
What is Prod1
It is a GPI protein and if you treat cells with antibodies against it, the cell will remain adhered to the same cell type as them- could be a factors influencing differential adhesion
What is the role of RA in the blastema
RA can change distal cells into proximal ones
What is the role of innervation in limb regeneration
In a normal limb, innervation is required, unless there was no innervation in the first place
What is newt anterior gradient
Can replace the nerve in supporting outgrowth
Binds to Prod-1.
It becomes expressed in the nerve in response to damage
Where is NAG expressed in the embryo?
In the epidermis
Innervation leads to downregulation
Aneurogenic limb has constant NAG which is why it can regenerate without a nerve
