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Tissues that do regenerate and tissues that don't
DO- blood, epithelial cells, skeletal muscle. DONT - most of the neurons in the CNS
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What is regeneration?
The capacity for a fully developed organism to replace tissues, organs and appendages, by growth or by repatterning.
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vertebrates that can regenerate new limbs
newts and urodele amphibians can regenerate limbs, tail, eye lens and some internal organs
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Zebrafish regeneration
Zebrafish can regenerate their heart which is a target for regnerative medicine
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Can mammals regenerate?
They can regenerate some of the liver after removal, and the tips of the fingers in humans.
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The two types of regeneration
Morphylaxis and epimorphis
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define morphylaxis
Little new growth, regeneration occurs by the repatterning of existing tissues and reestablishment of boundaries.
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Define epimorphosis
dependant on outgrowth of new structures
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What is involved in vertebrate limb regeneration
Cell de-differentation, then redifferentiation and growth.
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What happens immediately after newt limb amputation?
Rapid migration of epidermal cells over the wound surface, and a mass of undifferentiated cells called the blastema begins to form under the surface
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What forms the blastema
cells beneith the wound epidermis that lose their differentiation and start to divide. Derived locally from mesenchymal tissue of the stump.
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What protein appears to be important in providing an environement of dedifferentiation
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What does dedifferentiation of the muscle cells involve
expression of homeodomain transcription factor msx1,characteristic of undifferentiated mesenchymal cells.
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Do dedifferentiated cells remain true to type?
No - in newt, at least.
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Transdifferentiation in the axolotl tail
Muscle and catilige are produced by the transdifferentiation of glial cells that migrate from the spinal cord. This is a rare ectodermal to mesoderm transition
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Two things the growth of the blastema is dependant on
nerve supply and the overlying epidermis.
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What happens if nerves are cut before amputation
blastema forms but the limb fails to grow.
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How do we know it's not just the presence of nerves that helps the limb grow?
A completely aneurogenic limb will regrow if it's never seen nerves before. Unexplained
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Why can humans regenerate their digits
Connective tissue under the nail expresses MX1, A homeobox-containing gene that regulates BMP4 expression. MX1 is expressed in the progress zone
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What does 'morphogenic autonomy' mean
It can 'read' the position it's in and regenerate the appropriate structures distal from it. When transplanted - it grows from the position it was taken from
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Size comparison between limb bud and blastema
the blastema is 10x more cells - unlikely that factors diffuse across it like in development
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Blastema cells recognising a discontinuity in positional values
illustrated by grafting a distal blastema to a proximal stump. Gives a normal limb but the blastema only grows the hand. The arm grows by intercalary growth
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Molecular basis of the graded information
PROD1 is expressedin a graded manner along the proximal distal axis of the newt blastema.
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What does PROD1 do?
causes cells in the distal to be more tightly bound to each other.
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Another gene thought to play a part in positional identity
two Hoxa genes are expressed in the stump cells at the same time.
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What happens if you expose a regenerating limb to retinoic acid?
the blastema becomes proximalized. the limb regenerates as if it had been amputated at a more distal site.
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What happens if you up the dose of retinoic acid
The effect is amplified - high enough and you get an entire new limb
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How does retinoic acid work?
it probably increases the concentration of PROD1
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Retinoic acid in untreated regerating limbs
it is present in a set pattern but there is no evidence it is involved. the wound epidermis is a strong source of retinoic acid and there is a PD gradient in the blastema.
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What retinoic acid receptor is involved in proximo-distal changes?
the delta 2 receptor - activation of this proximalises cells.
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Insect leg regeneration intercallation
occurs proximo-distally and circumventrallyq
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How does the zebrafish regenerate it's heart
not by dedifferentiation - it uses the same mechanism as development - but at a low level so it's not identical. eg expression of the gene nkx2.5.
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What is regeneration?


The capacity for a fully developed organism to replace tissues, organs and appendages, by growth or by repatterning.

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vertebrates that can regenerate new limbs


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Zebrafish regeneration


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Can mammals regenerate?


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