Wednesday, December 27, 2006

 

How does a zebrafish grow a new tail?

If a zebrafish loses a chunk of its tail fin, it'll grow back within a week. Like lizards, newts, and frogs, a zebrafish can replace surprisingly complex body parts. A tail fin, for example, has many different types of cells and is a very intricate structure. It is the fish version of an arm or leg.

The question of how cold-blooded animals re-grow missing tails and other appendages has fascinated veterinary and medical scientists. They also wonder if people, and other warm-blooded animals that evolved from these simpler creatures, might still have untapped regenerative powers hidden in their genes.

People are constantly renewing blood components, skeletal muscles and skin. We can regenerate liver tissue and repair minor injuries to bone, muscle, the tips of our toes and fingers, and the corneas of our eyes. Finding out more about the remarkable ability of amphibians and fish to re-grow complex parts might provide the information necessary to create treatments for people whose hearts, spinal cords, eyes or arms and legs have been badly hurt.

Scientists have discovered some of the genes and cell-to-cell communication pathways that enable zebrafish to restore their tail fins.

'The ability to regenerate body parts such as those that are damaged by injury or disease,' said Dr. Randall Moon*, professor of pharmacology at the University of Washington (UW), an investigator of the Howard Hughes Medical Institute, and a researcher in the UW Institute for Stem Cell and Regenerative Medicine, 'involves creating cells that can take any number of new roles. This can be done by re-programming cells that already have a given function or by activating resident stem cells.'

Continued at "How does a zebrafish grow a new tail?"

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Based on the journal Development paper:

Distinct Wnt signaling pathways have opposing roles in appendage regeneration

Cristi L. Stoick-Cooper, Gilbert Weidinger, Kimberly J. Riehle, Charlotte Hubbert, Michael B. Major, Nelson Fausto, and Randall T. Moon

Abstract

In contrast to mammals, lower vertebrates have a remarkable capacity to regenerate** complex structures damaged by injury or disease. This process, termed epimorphic regeneration, involves progenitor cells created through the reprogramming of differentiated cells or through the activation of resident stem cells. Wnt/beta-catenin signaling regulates progenitor cell fate and proliferation during embryonic development and stem cell function in adults, but its functional involvement in epimorphic regeneration has not been addressed. Using transgenic fish lines, we show that Wnt/beta-catenin signaling is activated in the regenerating zebrafish tail fin and is required for formation and subsequent proliferation of the progenitor cells of the blastema. Wnt/beta-catenin signaling appears to act upstream of FGF signaling, which has recently been found to be essential for fin regeneration. Intriguingly, increased Wnt/beta-catenin signaling is sufficient to augment regeneration, as tail fins regenerate faster in fish heterozygous for a loss-of-function mutation in axin1, a negative regulator of the pathway. Likewise, activation of Wnt/beta-catenin signaling by overexpression of wnt8 increases proliferation of progenitor cells in the regenerating fin. By contrast, overexpression of wnt5b (pipetail) reduces expression of Wnt/beta-catenin target genes, impairs proliferation of progenitors and inhibits fin regeneration. Importantly, fin regeneration is accelerated in wnt5b mutant fish. These data suggest that Wnt/beta-catenin signaling promotes regeneration, whereas a distinct pathway activated by wnt5b acts in a negative-feedback loop to limit regeneration.

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*Info on Randall Moon:

Randall Moon studies the biochemistry of the Wnt signal transduction pathways and the roles of these pathways in vertebrates. He is interested in understanding the normal mechanisms and functions of Wnt signaling and in using this understanding to develop insights into the roles of Wnt signaling in diseases. He is also interested in developing potential therapies, with an emphasis on regenerative medicine.

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**Info on Regeneration:

"...Regeneration occurs in many, if not all vertebrate embryos, and is present in some adult animals such as salamanders ( e.g. the newt and axolotl), hydra, horseshoe crabs and a type of mouse. [1] [2]. Mammals exhibit limited regenerative abilities, although not as impressive as salamanders. Examples of mammalian regeneration include antlers, finger tips and holes in ears. Finger tip regeneration has been well characterized, and these studies have resulted in the first demonstration of a genetic pathway controlling regeneration in a mammal. Several species of mammals can regenerate ear holes; a phenomenon that has been most studied in the MRL mouse. If the processes behind regeneration are fully understood, it is believed this would lead to better treatment for individuals with nerve injuries (such as those resulting from a broken back or a polio infection), missing limbs, and/or damaged or destroyed organs.

Regeneration of a lost limb occurs in two major steps, first de-differentiation of adult cells into a stem cell state similar to embryonic cells and second, development of these cells into new tissue more or less the same way it developed the first time [7]. Some animals like planarians instead keep clusters of non-differentiated cells within their bodies, which migrate to the parts of the body that need healing..."

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