Regeneration Flashcards
What are the 2 types of regeneration?
- Morphallaxis
- Epimorphosis
What is regeneration?
The ability of a fully developed organism to replace organs/appendages by growth or repatterning
Is the ability to regenerate linked to the complexity of the organism?
No
What is morphallaxis? (2)
- No new cells/no growth
- Existing cells change their fate to restore the patterning
What is epimorphosis?
New cells grow to replace the missing parts
What kind of regeneration is demonstrated in hydra?
Morphallaxis
What are the features of hydra? (4)
- Only ectoderm and endoderm, no mesoderm
- Head region and basal region
- Split into positional values
- Constantly losing and regrowing cells meaning cells are constantly adjusting to a new positional value
What 2 gradients are involved in head regeneration in hydra?
- Gradient in positional value
- Head inhibitor gradient
What does the gradient in positional value in hydra determine? (2)
- Head inducing ability
- Resistance to a head inhibitor
What is the head inhibitor gradient in hydra?
High levels of head inhibitor molecule is produced just below the head, diffuses down to inhibit head formation elsewhere
What is the evidence for a head inhibitor gradient? (3)
- Graft a piece of tissue from just below the head onto the body of another hydra = no head formed because of the head inhibitor gradient in the recipient
- Remove head from the recipient = remove the head inhibitor gradient = head forms from the transplant
- Transplant the region to the basal area of the recipient = head forms because the gradient is weak at the basal end of the hydra
What is the evidence for the effects of positional value/head inducing capacity? (3)
- Graft a piece of tissue from just below the head onto the body of another hydra = no head formed
- Remove head from donor and wait a bit before transplanting = head forms in recipient because the cells have started to increase their positional value to restore the head
- Remove more of the body from the donor and wait even longer before transplanting = head forms in the recipient again, needed to wait longer to increase their positional value
What signalling pathway is involved in determining the head region/top positional value? (2)
- Wnt/beta-catenin signalling
- Inhibition of GSK3beta (negative regulator of Wnt) causes nuclear accumulation of beta-catenin and induces head formation
What are the steps of limb regeneration in urodele (tailed) amphibians? (4)
- Amputation
- Epidermal cell migration to cover the wound
- Cells below the epithelium dedifferentiate and form a blastema
- Cells that dedifferentiate are dermis, cartilage and muscle
What makes multinucleated muscle cells dedifferentiate to perform limb regeneration? (3)
- Thrombin (protease)
- Msx1
- Phosphorylated pRb (becomes inactive to allow regeneration)
How does regeneration differ to development? (2)
- Involves different genes
- Regeneration occurs on a much physically larger scale than development
To what extent do cells dedifferentiate during regeneration? (2)
- Only partial dedifferentiation
- Some crossover between dermis and cartilage but cells mostly remain true to their type
What are the rules of limb regeneration? (4)
- Limb regeneration is always distal to the wound
- Always according to the positional value at the site of the wound
- Doesn’t simply regenerate the missing parts, regenerates everything that should be distal to the wound site
- Blastema has the positional values encoded into it somehow and only regenerates what its meant to
How is retinoic acid involved in regeneration? (2)
- Determines the positional value of the blastema (proximal/distal)
- Works via Rar delta 2, meis homeobox genes and upregulation of GPI linked protein prod1
How does innervation affect regeneration? (2)
- Denervation of limb before amputation prevents regeneration
- A completely aneurogenic limb regenerates normally after amputation
What is nAG? (2)
- Newt anterior gradient
- A protein which binds to prod1 and is expressed in the nerve sheath in response to wounding
How is nAG involved in regeneration? (3)
- Applying nAG to a denervated limb can replace the role of the nerve in supporting regeneration
- Innervation of a limb during development switches off epidermal nAG which is why an amputated denervated limb doesn’t regenerate
- An aneurogenic limb never has innervation so has persistent epidermal nAG expression
How does limb regeneration occur in insects? (3)
- Local sensing of discontinuity in positional values
- Missing positional values are regenerated irrespective of the overall structure
- Positional values are repeated in leg segments so graft of mid tibia to mid femur doesn’t cause regeneration of intermediate structures
What are examples of mammalian regeneration? (5)
- Young children/mice can regenerate the tips of digits after the nailbed
- Axons can regrow in the PNS in the presence of Schwann cells
- Very little regeneration in the CNS due to inhibition from glia, astrocytes and oligodendrocytes
- Schwann cells from the PNS can promote axon regeneration in the CNS
- Liver and ribs can undergo regeneration
How does heart regeneration occur in mammals? (3)
- Cardiomyocytes are present during damage but don’t divide
- Progenitors are present but don’t perform repair
- Scar formation and hypertrophy of the remaining muscle is maladaptive
How does heart regeneration occur in zebrafish? (5)
- Heart can be regenerated in a different process to during development
- Relies on dedifferentiating muscle cells
- Endo and epicardium signals are involved, epicardium covers the wound
- Neuregulin from the epicardium signals to induce proliferation in the myocardium
- Scar tissue forms if regeneration doesn’t occur effectively
What is neuregulin?
A growth factor which is important for heart regeneration
