ESSAY discuss mechanisms of planarian regeneration Flashcards
What is regeneration?
the reactivation of development in post embryonic life to restoring missing tissue
What are the 4 mechanisms of regeneration?
stem cell mediated regeneration
epimorphosis
morphallaxis
compensatory regeneration
Define stem cell mediated regeneraton
a stem cell can give rise to more differentiated cellular progeny by asymmetric cell division (Self renewal)
regrowth of hair
replacement of red blood cells
define epimorphosis
dedifferentiation of adult structures to form an undifferentiated mass of cells that become re-specified e.g. regeneration of salamander limbs
define morphallaxis
regeneration occurs through repatterning of existing tissue with little new growth e.g. Hydra
define compensatory regeneration
differentiated cells divide but maintain their differentiated functions
e.g. mammalian liver
How do planarians regenerate?
Combination of mechanisms including neoblasts (Stem cells, epimorphosis, morphallaxis)
how long does it take planarians to regenerate?
Planarians exhibit a unique regeneration capacity as any small fragment from almost anywhere can regenerate a new organism in approximately 17 days
what happens after amputation?
neoblasts close to the wound proliferate, giving rise to the regenerative blastema, defined as the unpigmented tissues where the missing tissues will differentiate
The process of tissue regeneration in the wound region from proliferating neoblasts was termed _____
epimorphosis
A repatterning of the whole organism is required to produce a complete planarian, this process of remodelling old tissue was termed ______
morphallaxis
Describe terminal regeneration
After transverse sectioning the anterior end will regenerate the missing head, whereas the posterior end will regenerate the missing tail. this indicates that the remaining tissue is polarised and knows what is missing
Describe lateral regeneration
after longitudinal sectioning the old tissue regenerates the missing lateral half
Describe intercalary regeneration
after joining two distal pieces produced by transverse sections, planarians intercalate the missing region. In that case, cells from each piece participate equally in the production of an intercalary blastema
which 2 models can explain the mechanisms of regeneration in planarians?
positional information
polar co-ordinate
positional information is established how?
by a gradient of a chemical substance known as a morphogen
In the positional information how do cells know their positions?
by sensing concentration levels of the morphogen
Cells would know their polarity how?
by sensing the direction of the gradient
The positional information model divides organisms how?
into a number of regions, usually along the anterior posterior axis
The regions in the positional information model represent what?
different threshold levels of the morphogen
In the positional information model cells are thought to respond to the different threshold levels how?
by forming different structures at different thresholds
When was the polar co-ordinate model proposed?
1976
What does the polar co-ordinate model attempt to explain?
patterns of regeneration in three dimensions
what does the polar co-ordinate model state?
that cells recognise their position in the whole because of positional information that each cell receives designating where the cell is in relation to the rest of the organism
In the polar co-ordiante model how many pieces of information are required?
2
one that gives positional information along the anterior posterior axis and one that indicates position within the circumference
How is the information in the polar co-ordinate model thought to be coded?
Not in diffusible morphogens but in the molecules found on the surfaces of cells
how would you test the polar co-ordinate model?
remove a piece of the planarian
rotate the piece and then replace it
What should occur if the polar co-ordinate model is correct when you remove a piece and rotate it?
If you rotate it such that the ventral side is now dorsal, you will have inverted the clockface. The cells of the graft now have circumferential positional values that dont match those of its graft site.
the model predicts that there should be regeneration along the edges of the graft, even though technically you haven’t removed any tissue from the animal. If the model is correct, you should get duplication of structures in the region of the graft
After the head and tail of a planarian have been cut off what happens?
The anterior end of the remaining fragment regenerates a head, whereas the posterior end regenerates a tail
what indicates morphogen activity?
in general, planarians amputated at any level along the AP axis can regenerate a head; however, the rate of head regeneration decreases posteriorly and this indicates morphogen activity
Observations indicating morphogen activity led to what?
the so-called head-frequency curves and showed a time graded regeneration rate along the AP axis
What indicated that some minimal AP distance in a region of tissue is required to specify polarity?
in a set of classical experiments, narrow bipolar regenerating pieces occasionally regenerated 2 headed planarians
What has been shown recently about planarians and gradient activity?
Recently, a gradient of neoblast mitotic activity along the AP axis of intact planarians has been reported. However, a testable mechanistic framework of metabolic gradients in planarians remains to be developed
what is the Wnt/beta catenin signalling pathway?
it is an evolutionarily conserved mechanism that confers polarity during embryonic development
What leads to the disruption of the beta catenin degradation complex?
The binding of Wnts, the secreted elements of the pathway to the receptors frizzled and co receptors LRP
the beta catenin degradation complex is formed of what?
composed by axin, GSK3, CKI, APC
Afterwards beta catenin the key intracellular element of the pathway accumulates where?
in the cytoplasm, enters the nucleus, and activates TCF transcription factors, which regulate the expression of multiple genes
Two beta catenins have been reported from the planarian Schmidtea mediterranea. Explain this further
the silencing of one of them, Smed-bcatenin1 leads to an extreme phenotype - radial like hypercephalised. they have many eyes all around the planarian body.
this transformation occurs gradually in trunk pieces regenerating both head and tail regions
The severity of the phenotype depends not only on the time of regeneration in the RNAi experiment but also on what?
the level of Smed bcatenin1 inhibition as demonstrated after injection of varying amounts of dsRNA
what does injecting beta catenin do?
injecting beta catenine double stranded RNA, leads to destruction of the internal beta catenine RNA, which lowers the activity of the gene
with the lowest doses what occurs?
the phenotype observed is the inhibition of tail regeneration
as the dose increases what happens?
you get to the lower levels of beta catenin that cause heads to be produced hence the many eyed planarian
