Featured Research

from universities, journals, and other organizations

Organ Regeneration In Zebrafish: Unraveling The Mechanisms

Date:
November 10, 2009
Source:
Salk Institute
Summary:
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 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.

Unlike humans, zebrafish are able to regenerate amputated appendages.
Credit: Courtesy of the Salk Institute

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.


Story Source:

The above story is based on materials provided by Salk Institute. Note: Materials may be edited for content and length.


Cite This Page:

Salk Institute. "Organ Regeneration In Zebrafish: Unraveling The Mechanisms." ScienceDaily. ScienceDaily, 10 November 2009. <www.sciencedaily.com/releases/2009/11/091102171419.htm>.
Salk Institute. (2009, November 10). Organ Regeneration In Zebrafish: Unraveling The Mechanisms. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2009/11/091102171419.htm
Salk Institute. "Organ Regeneration In Zebrafish: Unraveling The Mechanisms." ScienceDaily. www.sciencedaily.com/releases/2009/11/091102171419.htm (accessed July 29, 2014).

Share This




More Plants & Animals News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) — West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) — Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
Asteroid's Timing Was 'Colossal Bad Luck' For The Dinosaurs

Asteroid's Timing Was 'Colossal Bad Luck' For The Dinosaurs

Newsy (July 28, 2014) — The asteroid that killed the dinosaurs struck at the worst time for them. A new study says that if it hit earlier or later, they might've survived. Video provided by Newsy
Powered by NewsLook.com
Raw: Sea Turtle Hatchlings Emerge from Nest

Raw: Sea Turtle Hatchlings Emerge from Nest

AP (July 27, 2014) — A live-streaming webcam catches loggerhead sea turtle hatchlings emerging from a nest in the Florida Keys. (July 27) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins