L7 - Regeneration Flashcards
Which cells live as long as the organism?
Neurones
Heart muscle
Which cells are replaced continuously by stem cells?
Blood
Epithelia
Which cells are replaced when tissue is damaged?
Skeletal muscle
What is regeneration?
Possibility of fully developed organism to replace organs by growth or repatterning
- Not linked to complexity of the organism
- Seen in flatworms and hydra
What are the two different types of regeneration?
Morphallaxis – repatterning without growth
Epimorphosis – regeneration by regrowth
What sort of regeneration do hydra show?
Morphallaxis
Simple organism with only two germ layers ectoderm and endoderm
Hydra grows continuously, therefore cells have to change their positional values or die
- Occurs at the tip of the tentacles, at the basal disc and by asexual budding
Repatterning also occurs during reproduction
What are the two gradients created during head regeneration in hydra?
Gradient in positional value which determines
- Head inducing ability
- Resistance to head inhibitor
Gradient in head inhibitor
When the head is removed it is reformed by respecifying existing cells
What experiment was used to show head inhibitor in hydra?
Shown by transplanting a piece of region 1 tissue to an intact hydra
Head inhibitor from existing head will prevent graft from forming a second head
If the donor head is removed the source of head inhibitor is lost and the graft can form a second axis
What experiment was used to show the effect of positional value/head inducing capacity in hydra?
If the head of a hydra is removed and after 6 hours region 1 is transplanted into the hosts body it can induce a head - it has gained a stronger head inducing capacity
Region 5 cannot do this - need to wait 30 hours before this region has a similar head inducing capacity
What happens if the head of hydra is removed?
If the head is removed the source of inhibitor is lost and will result in an increase in positional values
- The leftover tissue with the highest positional value will reach the head-value first
- It will start producing inhibitor restablishing the original situation only in a smaller body
How are Wnt and BetaCatenin signalling involved in hydra positional values?
Wnt signaling involved in head formation
- Wnt expressed in hydra head and in regenerating tip
Inhibition of GSK3β leads to upregulation of nuclear βcatenin – activating Wnt pathway
- If done in hydra or Xenopus all regions of the body acquire characteristics of head organizer
What are Urodele amphibians and what can they regenerate?
Urodele (tailed) amphibians can regenerate their dorsal crest, limbs, retina, lens, jaw and tail
Where does regeneration occur in urodele amphibians?
Regeneration occurs from a level that is appropriate to where the cut was made
- A distal amputation only regenerates distal structures
- A proximal amputation also regenerates proximal structures
What kind of regeneration is seen in the newt?
Epimorphic
Urodele limb regeneration method
- After amputation epithelial cells migrate over wound surface
- Regeneration is dependent on this
- Generation/regeneration have a different scale – morphogens involved need to work over a 10x larger range - Cells below the epithelium dedifferentiate forming a blastema
- Derived from the dermis, cartilage and muscle
- Multinucleate muscle cells can revert to mononucleate cells under the influence of thrombin
- Dedifferentiation of muscle cells involves- Expression of msx - homeobox transcription factor
- Inactivation of Rb gene - inhibits proliferation of muscle in normal circumstances
What is the exception to the very little transdifferentiation seen in urodele limb regeneration?
Dermis –> cartilage
What are the rules of regeneration?
Limb regeneration is always distal to the wound according to positional value at site of the cut
- Not just replacing missing parts
What is the evidence that limb regeneration is always distal to the wound?
If the distal limb of a newt is amputated and the stump is inserted into the flank and the limb is cut again, the anterior limb will regenerate the missing distal parts
The remaining stump will also regenerate a distal limb
What is the role of the wound blastema?
Reads the local positional value and generates more distal positional values
Has autonomy - once formed it can regenerate the structures lost in a different location
- If a distal blastema is transplanted to a proximal wound – entire limb will form
What is the cellular basis of positional value?
Proximal and distal blastema cells may sort via differential adhesion
If a distal is combined with a proximal blastema the proximal blastema will engulf the distal blastema
- A sign to the distal cells to stick more tightly to one another
Distally transplanted cells do not mix with proximal blastema cells that will form as a result of the intercalary regeneration
How is positional information encoded in the blastema?
Retinoic acid can reset a positional value to a more proximal value via
- Rarδ2
- Meis homeobox genes
- Upregulation of prod1 - expressed at the highest level in the proximal regenerating blastema
What is regeneration dependent on?
In a normal limb nerve innervation is required for regeneration to occur
- Except if the limb had no nerve in the first place
What is the newt anterior gradient?
A protein that can replace the nerve in supporting outgrowth, binds prod1
Expressed in nerve sheath in response to wounding
Innervation leads to downregulation of epidermal nAG
What does a neurogenic limb express?
Persistent epidermal nAG expression
