Gilbert Weidinger:
Regeneration researcher
Text and Interview by Ruth Williams
ruth.williams@rockefeller.edu
Weidinger wants
to grow new limbs and organs.
Some vertebrates, such as fish, amphibians, and lizards, have the
ability to replace lost limbs and regenerate organs. Regeneration
requires the reactivation of signaling molecules that were used
during embryonic development. Weidinger has spent his career so far
studying aspects of zebrafish embryogenesis, including the role of
Wnt signaling molecules (1, 2), and has
more recently been investigating how these Wnt pathways are used to
rebuild zebrafish fins and hearts (3–5).
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Gilbert Weidinger
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The regenerative capacity of mammals is extremely limited, yet
mammals possess many of the developmental signaling molecules that
other vertebrates reactivate for regeneration, such as the Wnts. Why
is it then that regeneration pathways no longer function in mammals,
Weidinger wonders. By learning more about what controls Wnt signaling
and its involvement in regeneration in zebrafish, he hopes to find
clues.
After completing his postdoc with Randall Moon at the University
of Washington in Seattle in 2006, Weidinger moved to the University
of Dresden where he now leads his own research group.
STARTING OUT
Did you always want to be a scientist?
I don't think so, no. Actually, in high school I was leaning toward
politics. Then I was going back and forth deciding whether to study
science or politics. In the end, when I went to university (in
Salzburg, Austria), I thought, "Okay, I'll go try out both." In
Austria, you can sign up for courses and you don't have to decide
immediately what you want to do. I was so excited by my first biology
courses, however, that I decided I was not going to do any more
politics.
After university you did a Ph.D. with Erez Raz in Germany. What
made you choose his lab?
I really wanted to work with zebrafish. In my undergraduate studies,
I did a diploma thesis project on Xenopus frogs. We thought
back then that this was an old-fashioned model, and it would die
out—of course, that hasn't happened. But I thought, like a lot of
people, that zebrafish might be more versatile than frog, because you
can easily do genetic screens.
I actually applied for a Ph.D. position with Wolfgang Driever, who
was quite famous for his genetic screens in zebrafish. He didn't have
a position available, but luckily Erez had just started his own
little group in the same department.
What was your project?
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Mutant zebrafish (bottom) that fail to grow back their
chopped off tails help Weidinger to understand how
regeneration works.
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I started a project on germ cell development. Back
then, germ cells
had been studied mainly in invertebrates. Very
little was known about
vertebrates, except for the mouse.
Most invertebrates specify germ cells very, very early in embryogenesis,
but mice and other mammals induce germ cells much later (during
gastrulation). At the time, the indications were that germ cell
development in nonmammalian vertebrates might happen in a way more
similar to invertebrates than to mammals. And it turns out that it
does.
What's the benefit of studying nonmammalian vertebrates, such
as fish, if their germ cell development is so different from
mammals?
Actually, it turns out that a lot of the molecules that are involved
are conserved, and probably have similar functions, it's just that
they are needed at a different stage of development.
I think that it's important to study these differences in developmental
biology. For a long time, people have looked for the similarities
between species and have been excited to see that a lot of things
are conserved. And now it's time to try to figure out what are
the differences. Because, of course, there are differences—the
organisms look different, they have to develop differently at some
point.
MOVING STATESIDE
After your Ph.D., you did a postdoc with Randall Moon in Seattle.
What made you choose that lab?
I wanted to continue studying the early events of zebrafish embryo
development, and Randy had been doing great work showing that Wnt
signaling is very important for those kind of things.
I also really wanted to go to the U.S., so I only applied for
postdocs there. I felt it could be a great experience to live abroad
and to see how science and life work there.
Would you recommend a stint in the U.S. to non-U.S. scientists
who are thinking about doing a postdoc?
Yes. The breadth of choice for joining a great lab is bigger in the
U.S. There's more great science in the U.S., more world-class
science, because the funding is better and it's a bigger country.
There's very good science in Europe too, but it's more limited.
It was a great experience for me, and I think it's very useful to
see how science is structured, and how the universities are
organized. You gain a slightly different perspective.
When and why did you move to Dresden?
I just started here a year ago. It is really a great place in Germany
for cell biology. I'm at the Institute for Biotechnology. Dresden
also has the Max Planck Institute for Cell Biology and Genetics,
which is a great place. And there's a new research center for
regenerative therapies, which has received a lot of investment.
There's a lot going on there: new groups are being hired, new
professorships, the funding is very good.
There are also a lot of interactions among the institutes, which
is great. We share talks and have a common graduate school.
TINY FISH, BIG QUESTIONS
How have you found the first year, setting up your own lab?
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heart injury (arrow, left panel) repairs without a
trace (right panel) in zebrafish. Mammals lack the
regeneration process responsible for such scar-less
repair.
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It went pretty smoothly, so I'm happy. Of course,
it's a big change
from the way you work as a postdoc. I now
have the responsibility of
hiring people, dealing with the administration,
the budget, and all
those things. It's a steep learning curve,
but it was okay.
I was very lucky that I could share the fish facility with Michael
Brand's lab (the director of this institute). Building a fish
facility is a lot of work and can take a lot of time. But all I had
to do was move my fish from the U.S.
Did you take them on the plane? Did you give them the window
seat?
[Laughs.] No, you send them in the post as live embryos. You
send them when they're one day old, they arrive a couple days later,
and when they're five days old, you need to start feeding them. So,
there's a convenient window of five days in which to post them.
What are you currently studying in these fish?
The big question for me now is regeneration. How does it work, what
are the molecular mechanisms that regulate it? I'm mainly interested
in epimorphic regeneration, which is the regeneration of complex
organs and limbs—in our case, the fins or the heart of the fish.
We're trying to figure out how these things work, how they're
regulated, and why lower vertebrates are much better than mammals at
regenerating. In mammals, the liver regenerates well, but all the
other organs essentially don't. In lower vertebrates—fish and
amphibia—the heart can regenerate, so can the spinal cord, the brain,
the retina, the lens, the kidney.
Maybe some of the signaling mechanisms that the lower vertebrates
use are just not being activated in mammals. Maybe mammalian cells
are competent for regeneration, but they're not receiving the right
signals in response to injury. If we find out what the signals are in
lower vertebrates, maybe one of the next steps would be to test those
signals in mammals.
If one knows more about the mechanisms, one can actually think
about therapies that might activate mechanisms that are dormant in
mammals.
References
- Weidinger, G., and R.T. Moon. 2003. J. Cell Biol.
162:753–755.[Abstract/Free Full Text]
- Weidinger, G., et al. 2005. Curr. Biol. 15:489–500.[CrossRef][Medline]
- Stoick-Cooper, C.L., et al. 2007. Development.
134:479–489.[Abstract/Free Full Text]
- Ueno, S., et al. 2007. Proc. Natl. Acad. Sci. USA.
104:9685–9690.[Abstract/Free Full Text]
- Stoick-Cooper, C.L., et al. 2007. Genes Dev.
21:1292–1315.[Abstract/Free Full Text]
