Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Unraveling the mechanisms behind organ regeneration in zebrafish

03.11.2009
The search for the holy grail of regenerative medicine—the ability to "grow back" a perfect body part when one is lost to injury or disease—has been under way for years, yet the steps involved in this seemingly magic process are still poorly understood.

Now researchers at the Salk Institute for Biological Studies have identified an essential cellular pathway in zebrafish that paves the way for limb regeneration by unlocking gene expression patterns last seen during embryonic development. They found that a process known as histone demethylation switches cells at the amputation site from an inactive to an active state, which turns on the genes required to build a copy of the lost limb.

"This is the first real molecular insight into what is happening during limb regeneration," says first author Scott Stewart, Ph.D., a postdoctoral researcher in the lab of Juan Carlos Izpisúa Belmonte, Ph.D., who led the Salk team. "Until now, how amputation is translated into gene activation has been like magic. Finally we have a handle on a process we can actually follow."

Their findings, which will be published in a forthcoming issue of Proceedings of the National Academy of Sciences, U.S.A., help to explain how epimorphic regeneration—the regrowing of morphologically and functionally perfect copies of amputated limbs—is controlled, an important step toward understanding why certain animals can do it and we cannot.

"Our experiments show that normal development and limb regeneration are controlled by similar mechanisms," explains Izpisúa Belmonte, a professor in the Gene Expression Laboratory. "This finding will help us to ask more specific questions about mammalian limb regeneration: Are the same genes involved when we amputate a mammalian limb? If not, what would happen if we turned them on? And if we can affect these methylation marks in an amputated limb, what effect would that have?"

The Belmonte lab uses zebrafish, a small fish from the minnow family, to study limb regeneration. "If you amputate the tail of the zebrafish, it regenerates in about a week, seemingly with no effort and leaving no scar," explains Stewart. "What's more, it regenerates a perfect copy and—like growing grass—it will do this over and over again."

Since regeneration recapitulates in broad strokes embryonic development, during which a complex multi-cellular organism develops from a handful of embryonic stem cells, the researchers began by comparing gene expression patterns between the two processes. During development, genes within specific cell types are turned on and off to trigger the necessary expression patterns that create a whole animal. Once their job is done, they lie silently till they are turned on once again following amputation.

Based on these similarities, Stewart reasoned that genes involved in regeneration may share silencing mechanisms with the ones active in embryonic stem cells. Embryonic stem cells are maintained in a ready-to-go state, "poised" for action to become whatever cell type is needed. The key to this "poised" state are histones, DNA packaging proteins that are also used as carriers for chemical modifications, such as methylation and acetylation. These chemical marks serve as "on" and "off" switches for specific genes.

Stewart discovered that the histone modifications that poise embryonic stem cell–specific genes for activation are also found on the histones near genes involved in regeneration, putting them into a ready-to-go state. "This suggests that two different gene expression programs may exist; one for normal cellular activity and one for regeneration," explains Stewart. To test this hypothesis, the team looked at the histone marks during regeneration. As suspected, they saw a reduction in "off" switches and an increase in "on" switches in regenerating tissue, tipping the balance toward gene expression.

Delving deeper, the researchers found that enzymes that remove the "off" mark, so-called demethylases, are present in high levels in regenerating tissue. One enzyme in particular, called Kdm6b.1, is found exclusively in cells that are undergoing the regeneration process. Without Kdm6b.1, zebrafish failed to regenerate amputated fins, meaning removal of the "off" mark is a prerequisite for fin regeneration.

In the long term, the Salk researchers hope that these findings will help them understand whether we can affect the outcome of mammalian limb regeneration. In the more immediate future, the team plans to use global approaches to identify all the targets of Kdm6b.1 during regeneration, and to find out what gives the signal to turn these genes off when regeneration is complete.

In addition to Stewart and Izpisúa Belmonte, Zhi-Yang Tsun, also contributed to the study.

The study was funded in part by the California Institute for Regenerative Medicine, the Fundacion Cellex, the G. Harold and Leila Y. Mathers Charitable Foundation, the Ipsen Foundation, and the National Institutes of Health.

About the Salk Institute for Biological Studies:

The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes, and cardiovascular disorders by studying neuroscience, genetics, cell and plant biology, and related disciplines.

Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.

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

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>