Lecture 8: Regeneration

* Define morphallaxis and epimorphosis. * Explain regeneration by morphallaxis in Hydra. * Describe cellular events during epimorphic regeneration. * Understand dedifferentiation and transdifferentiation in regeneration. * Identify key molecules involved in regeneration. * Compare mechanisms of heart regeneration in fish and mammals.

What is regeneration?

Regeneration is the ability of an adult organism to replace lost body parts by growth or repatterning following damage or injury.

Name the two major forms of regeneration discussed in the lecture.

The two forms are morphallaxis and epimorphosis.

Compare morphallaxis and epimorphosis.

Morphallaxis occurs mainly through repatterning of existing tissues with little or no growth, whereas epimorphosis involves growth and formation of new tissue.

Why is regeneration not linked to organismal complexity?

Simple organisms can regenerate entire structures while more complex organisms may show limited regeneration, meaning regenerative ability does not directly correlate with complexity.

Why is Hydra used as a model for morphallaxis?

Hydra regenerates without requiring growth and continuously changes cell positional values during growth and reproduction.

Why does Hydra possess strong regenerative capacity?

Hydra cells continuously undergo positional changes and tissue repatterning, allowing flexibility during regeneration.

Why is growth not required for regeneration in Hydra?

Hydra regenerates mainly by reorganising existing tissues and positional information rather than generating large amounts of new tissue.

Describe the two gradients involved in Hydra head regeneration.

Hydra head regeneration involves a positional value gradient and a head inhibitor gradient.

What determines head-inducing ability in Hydra?

Positional value determines head-inducing ability and resistance to inhibition.

What role does the head inhibitor play in Hydra regeneration?

The head inhibitor suppresses inappropriate head formation and helps regulate body patterning.

Describe the experiment demonstrating the role of the Hydra head inhibitor.

Grafting tissue near the head into another Hydra normally fails to induce a secondary axis because the inhibitor prevents head formation. Removal of the host head removes the inhibitor source and can permit secondary head formation.

Explain the relationship between Wnt/β-catenin signalling and Hydra regeneration.

Wnt/β-catenin signalling may establish high positional values at the head region and regulate organiser activity.

What effect does GSK3β inhibition have in Hydra?

GSK3β inhibition increases nuclear β-catenin levels, causing tissues to acquire characteristics of a head organiser.

What is epimorphosis?

Epimorphosis is regeneration through growth involving formation of new tissues following injury.

Which organisms were highlighted as examples of epimorphic regeneration?

Urodele amphibians such as newts and salamanders were highlighted.

What is the first major event after limb amputation in urodele regeneration?

Epidermal cells migrate across the wound surface to form a wound epithelium.

Why is epidermal migration important during limb regeneration?

Regeneration depends on epidermal migration because it establishes conditions needed for subsequent regenerative events.

What is a blastema?

A blastema is a mass of proliferating dedifferentiated cells formed beneath the wound epithelium during regeneration.

How are blastema cells formed?

Cells beneath the epithelium dedifferentiate and contribute to blastema formation.

Which tissues contribute cells to the blastema?

Dermis, cartilage, muscle and other tissues contribute cells during regeneration.

What is dedifferentiation?

Dedifferentiation is the process in which specialised cells lose aspects of differentiation and return to a less specialised state.

What is transdifferentiation?

Transdifferentiation is conversion of one differentiated cell type directly into another differentiated cell type.

Was transdifferentiation extensive during limb regeneration?

No, transdifferentiation was limited and most tissues largely remained true to type.

Give an example of limited transdifferentiation discussed in the lecture.

Dermis could contribute to cartilage and vice versa, but extensive lineage switching was uncommon.

How does fin regeneration compare with limb regeneration regarding cell fate?

During fin regeneration cells were largely observed to remain true to their original lineage.

State the first rule of regeneration described in the lecture.

Limb regeneration always occurs distal to the wound.

State the second rule of regeneration described in the lecture.

Regeneration depends on the positional value at the site of injury.

State the third rule of regeneration described in the lecture.

Regeneration does not simply replace missing structures but follows positional information rules.

What is morphogenetic autonomy after transplantation?

Transplanted tissues retain their own positional information and developmental behaviour.

How may blastema cells sort during regeneration?

Proximal and distal blastema cells may sort through differential adhesion mechanisms.

How does retinoic acid influence blastema identity?

Retinoic acid proximalises the blastema by altering positional identity through molecules including Rarδ2, meis genes and prod1.

Why is innervation normally required for limb regeneration?

Nerves provide signals necessary to support regenerative outgrowth.

What is nAG and what role does it play?

nAG (Anterior Gradient protein) can replace nerve function in supporting regeneration and binds prod1.

How does heart regeneration differ between zebrafish and mammals?

Zebrafish regenerate heart tissue through dedifferentiating muscle cells whereas mammals mainly undergo scarring and maladaptive hypertrophy.

Describe the role of Neuregulin in heart regeneration.

Neuregulin may act as a signal from the epicardium that stimulates proliferation of myocardial cells during regeneration.

Why are neonatal mice important in regeneration studies?

Neonatal mice can regenerate their hearts and loss of this ability correlates with loss of Erbb2, a Neuregulin co-receptor.