Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Starting over: Wnt reactivates dormant limb regeneration program

21.11.2006
Chop off a salamander's leg and a brand new one will sprout in no time. But most animals have lost the ability to replace missing limbs. Now, a research team at the Salk Institute for Biological Studies has been able to regenerate a wing in a chick embryo – a species not known to be able to regrow limbs - suggesting that the potential for such regeneration exists innately in all vertebrates, including humans.

Their study, published in the advance online edition of Genes and Development on Nov. 17, demonstrates that vertebrate regeneration is under the control of the powerful Wnt signaling system: Activating it overcomes the mysterious barrier to regeneration in animals like chicks that can't normally replace missing limbs while inactivating it in animals known to be able to regenerate their limbs (frogs, zebrafish, and salamanders) shuts down their ability to replace missing legs and tails.

"In this simple experiment, we removed part of the chick embryo's wing, activated Wnt signaling, and got the whole limb back - a beautiful and perfect wing," said the lead author, Juan Carlos Izpisúa Belmonte, Ph.D., a professor in the Gene Expression Laboratory. "By changing the expression of a few genes, you can change the ability of a vertebrate to regenerate their limbs, rebuilding blood vessels, bone, muscles, and skin - everything that is needed."

This new discovery "opens up an entirely new area of research," Belmonte says. "Even though certain animals have lost their ability to regenerate limbs during evolution, conserved genetic machinery may still be present, and can be put to work again," he said. Previously, scientists believed that once stem cells turned into muscles, bone or any other type of cells, that was their fate for life – and if those cells were injured, they didn't regenerate, but grew scar tissue.

Manipulating Wnt signaling in humans is, of course, not possible at this point, Belmonte says, but hopes that these findings may eventually offer insights into current research examining the ability of stem cells to build new human body tissues and parts. For example, he said Wnt signaling may push mature cells go back in time and "dedifferentiate" into stem-like cells, in order to be able to then differentiate once more, producing all of the different tissues needed to build a limb.

"This is the reverse of how we currently are thinking of using stem cells therapeutically, so understanding this process could be very illuminating," he says. "It could be that we could use the Wnt signaling pathway to dedifferentiate cells inside a body at the site of a limb injury, and have them carry out the job of building a new structure."

Members of the Wnt gene family (for "wingless," originally discovered in fruit flies) are known to play a role in cell proliferative processes, like fetal growth and cancer development, and Belmonte's lab has characterized the crucial role of Wnt signaling in limb growth. In 1995, the Salk researchers were first to demonstrate that they could induce the growth of extra limbs in embryonic chicks, and in 2001, they found that the Wnt signaling system played a critical role in triggering both normal and abnormal limb growth.

The current study was designed to see if Wnt signaling also was involved in the regeneration of limbs and included three groups of vertebrates: zebrafish and salamanders, which can regenerate limbs throughout their lives; frogs, which can only regenerate new limbs during a limited period during their fetal development; and chicks, which cannot regenerate limbs.

To manipulate animals' regeneration ability, the Salk researchers used inhibitory and excitatory factors for Wnt signaling, which they delivered directly to the remaining bulge after they cut a limb from the experimental embryos.

In adult zebrafish and salamanders, they found that blocking Wnt signaling with the inhibitory factors, prevented normal regeneration. And, conversely, when they treated mutant adult zebrafish that cannot regenerate with the excitatory agent, the ability to regenerate their fins was rescued, Belmonte says.

Using an inhibitory agent on frogs before the regeneration-enabled developmental window closed resulted in loss of that ability, but treating them with the excitatory agent after they had lost their regenerative capacity induced new limb growth.

They then performed the key experiment, successfully testing the ability of an excitatory factor to produce limb regeneration in chick embryos. "The signal restarted the process, and genes that were involved in the initial development of the limb were turned back on," Belmonte says. "It is simply amazing."

The procedure was tricky, however. Belmonte noted that if Wnt signaling is activated for too long of a period in these animals, cancer results. "This has to be done in a controlled way, with just a few cells for a specific amount of time," he says. "The fact is that this pathway is involved in cell proliferation, whether it is to generate or regenerate limbs, control stem cells, or produce cancer."

Gina Kirchweger | EurekAlert!
Further information:
http://www.salk.edu

Further reports about: Belmonte Embryo Regeneration Wnt Wnt signaling excitatory regenerate stem cells

More articles from Life Sciences:

nachricht Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology

nachricht Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Osaka university researchers make the slipperiest surfaces adhesive

18.10.2017 | Materials Sciences

Space radiation won't stop NASA's human exploration

18.10.2017 | Physics and Astronomy

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>