Lecture 10 - Regeneration

What is regeneration?

The REACTIVATION of developmental mechanisms after development has occured to restore damaged tissue

What are the 5 steps when thinking about regeneration

1. An initial idea of your identity, morphological map

2. Capable of recognizing a change and what is required to fix the change

3. be able to close the wound

4. Reactivation of development; cell proliferation, tissue growth, and repatterning of cells to replace lost structure

5. End of regeneration following completion

What are the 4 types of regeneration?

1. stem cell mediated

2. epimorphosis

3. morphallaxis

4. compensatory regeneration

Stem cell mediated regeneration

Routine making of new cells to replace ones as they die, examples are hair stem cells and bone marrow

Epimorphosis regeneration

Dedifferentiation of adult structure to form an undifferentiated mass of cells, that are capable of redifferentiating into the new structure (become less specific so that they can create multiple cell types to replace what was lost), this is seen in amphibian limbs

Morphallaxis regeneration

TRansdifferentiation, no cell death or cell growth, just cells turning into different cell types (less of each cell type, but some of each), seen in hydra

Compensatory regeneration

The cell starts proliferating again, so one cell just making more of itself, seen in the mammalian liver

How is regeneration and development similar

They both utilize stem cells and the processes of cell proliferation, differentiation, and tissue morphogenesis

How is regeneration and development different

regeneration is response to injury and an immune response which is not present in development, uses different programs and it is induced by immune response, requires communication and integration between the old and new tissue systems, also communication as to size dont want to be making anything bigger or smaller then before so the cells need to communicate

Which to cell layers make up hydra?

The endo and ectoderm, which are constantly undergoing cell displacement (as cells are being lost, new ones are being replaced to make up for the lost ones)

What 3 types of stem-like cells are essential in hydra

1. unipotent endodermal cells

2. unipotent ectodermal cells

3. multipotent interstitial stem cells, contained in ectodermal layer but produces many neurals and other specialized cells

How is head/foot axis orientation controlled

There is a hypostome present in the head region that creates a head activation gradient, and a foot activation gradient at the basal disc. The presence of either is sufficient for development of either structure.

Importance of the hypostome

If moved can produce a head wherever it is placed, produces the activation signal for head production, only sef-differentiating region of the hydra, als produces a signal to stop the formation of new head organizers

What proteins/morphogens are involved in the hypostome?

Wnt and B-catenin

two types of hydra regeneration

1. morphallactic regeneration

2. epimorphic regeneration

Morphallactic regeneration

if the cut is made just below the hypostome, transdifferentiation will occur (cells turn into different cells), no proliferation

Epimorphic regeneration

If cut occurs along the midsection interstitial cells undergo apoptosis below the cut site, then before dying produce a bunch of Wnt which activates B-catenin in the interstitial cells beneath them, this causes lots of proliferation in these stem cells which remodels the epithelial cells

limb regeneration in salamander

1. blood and immune cells flood the wound to make a clot

2. stem cells/ proliferation activated

3. epidermis cells migrate over the wound to form wound epidermis (without this no limb regeneration)

4. Epidermis thickens into the apical epidermal cap (AEC)

5. AEC signals progenitor cells to create the regeneration blastema underneath it, created through the dedifferentiation of other cells

6. Continued differentiation of blastema allows outgrowth of limb to regenerate

What type of cells are blastema cells?

They are restricted unipotent or progenitor cells that have restricted fates, so they have some memory of their previous state before dedifferentiation

What stimulates blastema growth?

The AEC stimulates the secretion of Fgf8 which stimulates growth, and the sensory and motor axons innervate the blastema, if denervation occurred before the limb was amputated then no new limb growth would occur

Is there a limit to regeneration?

Yes, the mechanisms and paracrine factors can be exhausted and therefore stop regrowth after too many amputations

Compensatory regeneration of the liver

The human liver regenerates through the proliferation and enlargement of existing tissues, and division of differentiated cells restore its function. Adult cells reenter the cell cycle and divide to replace the lost cells, and then progenitor cells become activated