Zebrafish in regeneration Flashcards
why are zebrafish interesting?
they are vertebrates
what is epimorpic regen?
- occurs in the newt limb being cut off and then the limb can regenerate: completely patterned limb
- blastema forms which contains intrinsic information required to re pattern the regenerating structure. The regeneration is dedifferentiation of cells or stem cell based.
what happens in the blastema during regen?
the epithelial cells of the blastema signals to the cells to dedifferentiate back to a primitive mesenchymal like cell and these proliferate- then they redifferentiate
what is compensatory growth?
- organs are able to compensate for damage
- instead of dediff and repatterining, the components are replaced but the liver isn’t repatterned - cells will grow and replace some of tissue
what is tissue regeneration as a regen method?
- local tissue regeneration and repair
- repair of one cell type
- good example is human skeletal muscle where the sat cells are stimulated and will proliferate and regen
what makes a good animal model for regeneration?
Easy to breed • Easy to maintain in the lab • Genetically tractable • Bear some relationship to man • Good natural regeneration capacity
why are mammals rubbish at regen?
- the only thing that a mammal can regenerate is the deer antler via an epitmorphic process
- the others are very poor
what can zebrafish regenerate?
- heart, liver, fins, spina cord and kidney, brain and eye
why is bad transparency bad for a model?
can’t do lineage tracing of cells during regen
why is it hard to use invertebrates in invertebrate models?
they dont always have analogous tissues
are vertebrate lineages quite autologous?
yes
why are deer bad in terms of breeding?
they breed seasonally
what little thing is good for regen?
the planaria
what is bad and good about the plenaria?
they are not very similar to humans
what is hard about using a newt?
hard to make KO- not very genetically tractable
how long can a tail fin take to regen generally?
around 7 days
what type of regen occurs int he tail fin?
epimorphic regeneration- de diff and re diff of tissues = from the cut ray- the osteoblasts
how did they find out which genes were involved in fin regeneration?
they carried out a screen
what factors are involved in fin regen? what does this resemble?
Fgf, WNT in the blastema
fgf shh and cell cycle regulator in outgrowth
BMP and runx2 in rediffereniation
- the development
how can you label a heart in the ZF?
use promoter to drive the heart
what are the 3 ways to injure the heart?
- ventricular resection
- cryoinjury - cold probe
- genetic cardiomyocyte ablation
what is the process of repair in the ZF heart?
- amputate, activation of blood clot which activates the endocardium lining and GF production, then fibrin clot forms which activates the pericardium which activate GFR and pathways to stimulate proliferation
- wihtin 7 days get activation of cardiomyocytes and start proliferating and new blood vessel formation
- within 30 days there is a repaired heart
hat factors that works in ZF heart regen doesn’t work in mammalian heart
BMP signalling driving proliferation
what is the role of the endocardium
first tissue responding, produces RA which also promotes regen
what is the role of the epicardium
Epicardium activation promotes angiogenesis through
production of growth factorsMammalian cardiomyocytes do not proliferate well but epicardium does secrete some growth factors
ow are ZF hearts different to mammals? why is this interesting
they are mononucleate
Mammalian embryonic/early postnatal hearts are mononucleate too.
• Mouse hearts will regenerate up to P7
• There are small pools of mononucleate cells in
mammalian adult hearts
how were mammal hearts made to rpoliferare
in the ZF injured heart miR26i are downrgelated but not in mammalian injured heart- theses were inhibited in mammal heart and started to proliferate
what do mammal muller cells do when they divide?
divide symmetrically and form a scar
