regeneration Flashcards

1
Q

DEFINE: morphallaxis

A

regeneration occurring by re-patterning of existing cells, causing a shift in fates. no change in cell number.

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2
Q

DEFINE: epimorphosis

A

growth zone formed at the position of the cut, causing proliferation and regrowth of missing parts of the structure

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3
Q

what gradients are involved in hydra head regeneration?

A
  • positional value gradient - head-inducing ability and resistance to head inhibitor
  • head inhibitor gradient (from head to basal disc)
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4
Q

which signalling pathway induces the head organiser?

A

wnt/β-catenin signalling pathway

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5
Q

regeneration of lens in urodele amphibian

A

lens (epidermal structure) is regenerated from iris (neuronal structure) by transdifferentiation

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6
Q

regeneration of limb in urodele amphibian

A
  1. amputation
  2. epithelial cells migrate over wound
  3. cells below epithelium dedifferentiate and form blastema
    blastema cells derived from dermis, muscle and cartilage
    > multinucleate muscle cells dedifferentiate back to mononucleate cells
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7
Q

which proteins drive regeneration in urodele amphibians?

A
  • pRb (inactive form) –> allows re-entry into cell cycle
  • thrombin - protease
  • msx1 - homeobox tf
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8
Q

experiment to show limb regeneration does not replace missing parts in amphibians

A
  1. cut limb
  2. insert stump of limb into belly to establish vascular connections
  3. cut limb again
  4. anterior limb regenerates structures distal to cut
    stump regenerates structures distal to cut and NOT a proximal humerus (proximal to radius and ulna)
    - 2 radii and ulnae formed
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9
Q

experiment to show limb has morphogenetic autonomy in amphibians

A
  1. animal 1 - cut close to body
    animal 2 - cut closer to hand
  2. label the blastema cells. remove proximal blastema cells and transplant distal blastema cells onto proximal wound
  3. distal blastema cells only form a hand
  4. remaining tissue formed by intercalary growth - site of wound senses discontinuity in positional values as positional value of blastema does not match cut site
  5. entire limb forms
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10
Q

why is regeneration dependent on innervation (unless limb had no nerve during early development ?

A

nerve sheath expresses nAG - replaces nerve in supporting outgrowth
nAG expressed in embryo epidermis. when it is innervated, epidermal nAG downregulated

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11
Q

what does nAG bind to?

A

prod1

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12
Q

what happens when proximal and distal blastemal cells are co-cultured?

A
  • sort by differential adhesion

proximal blastema cells more adhesive because they express more prod1 so they engulf distal blastema cells

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13
Q

which genes does proximalisation by RA occur via?

A
  • prod1
  • meis homeobox genes
  • rarδ2
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14
Q

give examples of mammalian regeneration

A
  • ribs can regenerate if periosteum intact
  • liver can regenerate
  • PNS axons can regenerate
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15
Q

what occurs when there is an infarction in a mammalian heart?

A
  • scar formation then rest of heart undergoes maladaptive hypertrophy –> increased risk of further infarction
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16
Q

which genes are expressed in a regenerating zebrafish heart but not an embryonic zebrafish heart?

A

msxB and msxC

17
Q

zebrafish heart regeneration mechanism

A
  1. cut at ventricle - heart bleeds profusely
  2. clotting
  3. endocardial activation. expresses raldh2 -> enzyme synthesising RA
  4. epicardial activation - epicardium moves to cover the wound. activates neuregulin
  5. neuregulin drives proliferation of myocardium
  6. newly formed muscle expresses fgf - stimulates epicardial cells to invade regenerated muscle and re-establish blood vessels in regenerating muscle
  7. clot dissolved + electrical coupling occurs
18
Q

DISEASE: cardiomegaly

A

GOF of neuregulin
drives proliferation and increase in cell number
massive hearts

19
Q

why do neonatal mice lose their ability to regenerate their hearts

A

loss of erbb2 = coreceptor for neuregulin

correlates with loss of neuregulin sensitivity