Thursday, December 28, 2006

How does a zebrafish grow a new tail?

December 27, 2006 - The answer may help treat human injuries

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

"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."

Developmental biologists know that a particular kind of cell-to-cell
communication, called Wnt/Beta-catenin signaling, regulates the fate
of these as-yet undeveloped cells as an embryo forms. Through a
cascade of signals, cells waiting for their calling learn which spot
to take to help form the embryo, what kinds of cells to become
there, and how many cells like themselves should be reproduced.
These streams of signals also tell stem cells in adult organisms
what functions to undertake. Once tissue formation starts, something
has to tell it to stop before growth gets out of hand.

In the Dec. 21, 2006 online edition of the scientific journal
Development, UW researchers report on laboratory evidence that
suggests that Wnt/Beta signaling also promotes the regeneration of
tail fins in zebrafish. Another, distinct signaling pathway
activated by a different kind of Wnt protein called Wnt5b, turns
down the genes that are turned on by Wnt/Beta-catenin, impairs cell
proliferation, and inhibits fin regeneration. Fish that have a
mutant Wnt5b protein regenerate missing tails very quickly. Too much
of another related protein, Wnt8, also increases cell proliferation
in the regenerating fin.

"We can actually increase the rate of regeneration by turning on
these genes," Moon said.

The researchers also noted, "We show that Wnt/Beta-catenin signaling
is activated in the regenerating zebrafish tail and is required for
the formation and subsequent proliferation of the progenitor cells
of the blastema." A blastema is a little nub of cells that directs
regeneration, much like the conductor of an orchestra. By directing
cell communication, these few cells grow into an organ or body part,
in this case, a tail fin.

"It is most likely the inability of humans to form a blastema in the
first place that renders us unable to re-grow arms and legs," said
Cristi Stoick-Cooper, a graduate student in the multidisciplinary
Neurobiology and Behavior program at the UW, who, with Gilbert
Weidinger, now of the Technical University of Dresden (TUD),
Germany, was first co-author of the study. The research was done in
Moon's lab.

"Our study is the first to identify a gene (Wnt5b) that inhibits
regeneration," said Weidinger, a former UW postdoctoral fellow who
leads the Wnt Signaling in Development and Regeneration research
group at the TUD's Biotechnology Center. "This is very exciting,
because this gene might also inhibit regeneration in mammals and
man. So, if we find ways of interfering with the function of Wnt5b,
we might be able to promote regeneration."

Moon added that, because the same genes for turning on and turning
off growth and development are found in humans, and drugs exist that
can regulate this pathway, the findings are directly relevant to
future testing of whether scientists can increase the capacity of
humans to re-build damaged organs.

University of Washington

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