9c.1 Regeneration Flashcards

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1
Q

How much can they regenerate?

  • Hydra
  • Planaria
  • amphibian and fish
  • deer
  • mammal
A
  • Hydra: entire individual from small fragment
  • Planaria: whole anterior and post halves of body
  • amphibian and fish: full limbs, tail, fins, lens, CNS, heart and more
  • deer: antlers
  • mammal: some organs
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2
Q

Regeneration 101

A
  • Renewal of existing tissues.
  • Reactivation of development in postembryonic life to restore missing or damaged tissues.
  • Regeneration is common in animal kingdom, more prevalent in the invertebrates than mammals.
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3
Q

Four different modes of

regeneration

A
  1. Stem cell mediated regeneration
  2. Epimorphosis
  3. Morpallaxis (transdifferentiation)
  4. Compensatory Regenration
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4
Q

Stem cell mediated regeneration

A

•multipotent stem cell undergoes differentiation into an number of things it could be, or unipotent stem cell becomes differentiated into the specific one thing
•specific replacement of
lost tissues
•Ex: blood cells (haematopoiesis); digestive tract epithelium; hair shafts;
planarian flatworms

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5
Q

Epimorphosis

A

•full differentiated cell undergoes dedifferntiation then this multipotent undergoes differentiation
•“dedifferentiation” and “re-differentiation”
of cells at wound sites.
– De-differentiation is differentiated cells form relatively
undifferentiated mass of cells that later re-differentiates to form new
structures.
– Ex: amphibian and insect limbs

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6
Q

Morpallaxis

A
  • transdifferentiate into different cell types. Example, epithelium becomes neuron. •Repatterning from existing tissue with no new growth
  • Ex: hydra regeneration
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7
Q

Compensatory Regenration

A

•different cells are induced to divide and you increase the number, but they maintain their differentiated functions. Each cell produces cells similar to itself.
•re-patterning of existing tissues without new
growth.
Ex: mammalian liver

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8
Q

Regeneration in Planaria

A
  • In planarian flatworms, regeneration is a kind of stem-cell mediated event, and occurs in a way that suggest a morphogen gradient is at work in the regeneration that is observed.
  • At the cut surface clonogenic neoblasts (pluripotent stem cell) direct development of the missing structures—heads make tails, and tails make heads.
  • Colognenic neoblasts migrate to the site of wound and regenerate the tissues.
  • One cologenic neoblast is sufficient to regenerate into head or tail region.
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9
Q

Flatworm regeneration and its limits

A
  • cut in 3, each piece can develop into entire planeria

- if middle piece too small, gets confused and abnormal regeneration since no discerable gradient and maybe 2 heads form

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10
Q

Irradiation of planaria:
1750 rads
6000rads with transplanted noblest

A

1750 rads: kills almost all neuroblasts. If one colonogenic neoblastsurvives, it can divide to generate a colony of dividing cells

6000rads: eliminates all dividing cells / Transplant one single clonogeneic neoblast from donor. Restores all cells in organism and restores its capacity to divide

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11
Q

Polarity in Planaria regeneration: DV and Ant-Post

A

DV Axis:
•BMP defines the dorsal region in flat worms.
•Noggin in the Ventral

Anterior Posterior:
•Anterior posterior polarity is regulated by Wnt and β-catenins.
•β-catenin is activated by Wnt in the posterior regions (generating tail).
•Repressors of Wnt prevent β- catenin production in the anterior– facing regenerating neoblast cells.
•If Wnt pathway is blocked in the posterior blastema then the result is a worm with heads at both the ends.

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12
Q

Two possible mechanisms for neoblast specification during regeneration

A

1)
•pluripotent neoblast cell gets activated by injury
•becomes multipotent post mitotic blastemacell
•geys wound specific signal and differentiates

2)
•pluripotent neoblast cell gets regiional signal before injury
•becomes multipotent regional lineage restrictedproginators
•gets wond specific signal
•becomes unipotent post mitotic blastema precureser
•differetiates

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13
Q

Epimorphic regeneration of salmander limbs

A

•Relatively undifferentiated cells arise from originally differentiated tissue, which then proliferates and re-differentiates into new
limb parts.
• Bone, dermis, cartilage and muscles contribute to the regeneration blastema.

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14
Q

Upon amputation of salamander limb

A

•plasma clot forms at the site of injury.
• epidermis from the stump migrate and form wound epidermis.
• Nerves innervating the limb
degenererate for a short distance proximal to the plane of amputation.
• Extracellular matrices are
degenerated by protease and single cells that undergo dedifferentiation are formed.
• These cells redifferentiate to form new structures of the limb.
• Wound epidermis thickens to form AER equivalent structure called apical ectodermal cap (AEC).
•cut wait 72 days whole limb regrown
•AEC much bigger than AER
•accumulation of blaster under AEC

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15
Q

Regeneration of larval forelimb of salamander

A

(A). Skin and muscle cells have retracted from the tip of humerus.
(B). 5 d later accumulation of
blastema cells seen beneath the AEC.
(C). 7d a large population of
mitotically active blastema cells lie distal to humerus.
(D). 8d Blastema cells elongate by mitosis and dedifferentiation has occurred.
(E). 9d Early re-differentiation seen.
(F). Formation of
precartilagenous structures.

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16
Q

Blastema is similar to progress zone of developing limb

A
  • The anterior-posterior axis is established by sonic hedgehog activation and HoxD gene activation, just as in limb buds
  • Proximal-distal axis is established by interactions between HoxA gene activti’on and retinoic acid (RA)
  • The most distal cells are fated to become autopod structures
  • A transplanted limb blastema can substitute for an AER on a developing limb
  • The full ‘nested’ Hox gene pacern is restored during regeneration, and is influenced by RA which PROXIMALIZES blastema cells