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 How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>