Regeneration
Hello friends of Biology & Genetics. This will be the first Sticky Topic on a specific topic elected by your friendly Biology & Genetics moderator. I will not always start the sticky topic thread. Some times I will pick an existing interesting thread and make it the sticky topic thread.
This months Sticky Topic is ‘Regeneration’. I will start myself with a rather specific introduction on a narrow topic. This does not mean that the discussion has to be limited to this narrow topic. Far from it! Feel free to meander and ponder!
Let me give you a few suggestions:
Regeneration in humans
Stem cells and regeneration therapies
Why do not all organs regenerate?
Woundhealing
Regeneration in science fiction
Future of regeneration?
trans- and de-differentiation
Lens regeneration
The lens is part of the eye that, along with the cornea, helps to refract light to focus on the retina (see the picture below). It is therefore rather an important structure. Without it we are not exactly blind, but all we see is a blur.
Once damaged it is gone. That is in most vertebrate species. However, not in all species! The newt is a salamander which can regenerate not only its eye lens, but also limbs and its spinal cord.
It isn’t really a recent discovery that the newt can regenerate its lens. There are three publications of different researchers ranging from the year 1880-1895 where this phenomenon was first described. That's more than 100 years ago. These researchers removed the lens and noticed it was completely regenerated.
The lens is regenerated by a process called transdifferentiation. A group of cells that is already committed to a specific cell fate or specialization returns to a ‘blank’ state and then differentiates into a new cell fate. This is a very special event. It doesn’t occur very often in complex organisms.
Some fish, avian and mammalian species also show lens regeneration, but the mechanism does not happen via transdifferentiation, but through another more complex mechanism.
In the figure below you see a summary of the events that occur during lens generation. After the lens is removed the iris pigment epithelial cells or PECs for short (that’s just how they are called) on the dorsal side start de-differentiating at the tip of the iris (1). Nothing much happens at the ventral side.
These dedifferentiated cells will now re-enter the cell cycle which simply means that they start proliferating once again. After a few cell divisions they will form a lens vesicle (2). At this point already cells at the inside start thickening (in orange) and the synthesis of crystallins starts. Crystallins are structural molecules typical of the lens. This process continues, the vesicle grows larger, and the inside is filled up with cells producing more crystallins (3). And finally the lens is almost fully formed (4).
In the newt the entire process takes about 25 days.
Genetic Control of Newt lens regeneration
I don’t really want to go to deeply into this subject here because I’m afraid it will pretty soon get too specialized to be of general interest. I will restrict myself here to discuss the role of Pax-6 in more general terms.
Pax-6 is a very interesting gene. It is a master regulator of eye development. Forced expression of this gene in the wrong place can lead to ectopic eyes. It is also very highly conserved between species. Mouse Pax-6 can trigger eye development in the fruitfly. Without Pax-6 there is no eye development.
It is also expressed in the dorsal and ventral iris. And as we might remember the tip of the dorsal iris is the place where lens regeneration starts in the newt with the de-differentiation of PEC cells. This pax-6 expression domain at this location also coincides with cellular proliferation during lens generation.
You cannot knock out pax-6 in the newt in a transgenic newt line like you might do in the mouse, because there is no transgenic technology available for the newt. However you can knock out a gene via other means. In one paper the researchers used morpholinos to knock down Pax-6 (ref: Rio-Tsonis 2006). Without Pax-6 expression cellular proliferation was diminished. Also crystalline production was reduced leading to a serious reduction in lens fibers.
It seems therefore that Pax-6 is not only needed to initiate eye development, also in eye regeneration it has a crucial role.
Literature.
Rio-Tsonis et al (2006) The role of Pax-6 in lens regeneration. PNAS, 103: p14848-14853
Rio-Tsonis and Tsonis (2003) Eye regeneration at the molecular Age. Developmental Dynamics 226: p211-224
Hello friends of Biology & Genetics. This will be the first Sticky Topic on a specific topic elected by your friendly Biology & Genetics moderator. I will not always start the sticky topic thread. Some times I will pick an existing interesting thread and make it the sticky topic thread.
This months Sticky Topic is ‘Regeneration’. I will start myself with a rather specific introduction on a narrow topic. This does not mean that the discussion has to be limited to this narrow topic. Far from it! Feel free to meander and ponder!
Let me give you a few suggestions:
Regeneration in humans
Stem cells and regeneration therapies
Why do not all organs regenerate?
Woundhealing
Regeneration in science fiction
Future of regeneration?
trans- and de-differentiation
Lens regeneration
The lens is part of the eye that, along with the cornea, helps to refract light to focus on the retina (see the picture below). It is therefore rather an important structure. Without it we are not exactly blind, but all we see is a blur.
Once damaged it is gone. That is in most vertebrate species. However, not in all species! The newt is a salamander which can regenerate not only its eye lens, but also limbs and its spinal cord.
It isn’t really a recent discovery that the newt can regenerate its lens. There are three publications of different researchers ranging from the year 1880-1895 where this phenomenon was first described. That's more than 100 years ago. These researchers removed the lens and noticed it was completely regenerated.
The lens is regenerated by a process called transdifferentiation. A group of cells that is already committed to a specific cell fate or specialization returns to a ‘blank’ state and then differentiates into a new cell fate. This is a very special event. It doesn’t occur very often in complex organisms.
Some fish, avian and mammalian species also show lens regeneration, but the mechanism does not happen via transdifferentiation, but through another more complex mechanism.
In the figure below you see a summary of the events that occur during lens generation. After the lens is removed the iris pigment epithelial cells or PECs for short (that’s just how they are called) on the dorsal side start de-differentiating at the tip of the iris (1). Nothing much happens at the ventral side.
These dedifferentiated cells will now re-enter the cell cycle which simply means that they start proliferating once again. After a few cell divisions they will form a lens vesicle (2). At this point already cells at the inside start thickening (in orange) and the synthesis of crystallins starts. Crystallins are structural molecules typical of the lens. This process continues, the vesicle grows larger, and the inside is filled up with cells producing more crystallins (3). And finally the lens is almost fully formed (4).
In the newt the entire process takes about 25 days.
Genetic Control of Newt lens regeneration
I don’t really want to go to deeply into this subject here because I’m afraid it will pretty soon get too specialized to be of general interest. I will restrict myself here to discuss the role of Pax-6 in more general terms.
Pax-6 is a very interesting gene. It is a master regulator of eye development. Forced expression of this gene in the wrong place can lead to ectopic eyes. It is also very highly conserved between species. Mouse Pax-6 can trigger eye development in the fruitfly. Without Pax-6 there is no eye development.
It is also expressed in the dorsal and ventral iris. And as we might remember the tip of the dorsal iris is the place where lens regeneration starts in the newt with the de-differentiation of PEC cells. This pax-6 expression domain at this location also coincides with cellular proliferation during lens generation.
You cannot knock out pax-6 in the newt in a transgenic newt line like you might do in the mouse, because there is no transgenic technology available for the newt. However you can knock out a gene via other means. In one paper the researchers used morpholinos to knock down Pax-6 (ref: Rio-Tsonis 2006). Without Pax-6 expression cellular proliferation was diminished. Also crystalline production was reduced leading to a serious reduction in lens fibers.
It seems therefore that Pax-6 is not only needed to initiate eye development, also in eye regeneration it has a crucial role.
Literature.
Rio-Tsonis et al (2006) The role of Pax-6 in lens regeneration. PNAS, 103: p14848-14853
Rio-Tsonis and Tsonis (2003) Eye regeneration at the molecular Age. Developmental Dynamics 226: p211-224
i used to catch those newts in my backyard as a youngster. fast little mofos, actually. maybe slow in comparison to other wildlife, but i can definitely say that it is hard for a 10 year old boy to grab one.