Featured Research

from universities, journals, and other organizations

Story of lymphatic system expands to include chapter on valve formation

Date:
November 15, 2011
Source:
St. Jude Children's Research Hospital
Summary:
Scientists have shown that a gene essential for normal development of the lymphatic system also plays a critical role in forming the valves that help maintain the body’s normal fluid balance.

A century after the valves that link the lymphatic and blood systems were first described, St. Jude Children's Research Hospital scientists have detailed how those valves form and identified a gene that is critical to the process.

The gene is Prox1. Earlier work led by Guillermo Oliver, Ph.D., a member of the St. Jude Department of Genetics, showed Prox1 was essential for formation and maintenance of the entire lymphatic vasculature. The lymphatic vasculature is the network of vessels and ducts that help maintain the body's fluid balance and serves as a highway along which everything from cancer cells to disease-fighting immune components moves.

Oliver is senior author of the new study, which appeared in the October 15 edition of the scientific journal Genes & Development.

The new research suggests that Prox1 is also essential for proper formation of the one-way valves that control movement of fluid and nutrients from the lymphatic system into the blood stream. Researchers found evidence that the Prox1 protein also has a role in formation of the venous valves.

"Understanding how valves form is crucial to efforts to develop treatments for valve defects that affect both children and adults," said the paper's first author, R. Sathish Srinivasan, Ph.D., a research associate in the St. Jude Department of Genetics. Those defects are linked to a variety of problems including lymphedema and deep vein thrombosis, which are blood clots that form deep in veins and have the potential for causing life-threatening complications. Lymphedema is the painful and sometimes disfiguring swelling that can occur when lymph flow is disrupted.

For more than a decade, the lymphatic system has been a focus of Oliver's laboratory. The laboratory's contributions through the years include evidence that leaky lymphatic vessels might contribute to obesity. Oliver and his colleagues also demonstrated how the lymphatic system forms from Prox1-producing cells destined to become lymphatic endothelial cells (LECs) when they leave the developing veins and migrate throughout the body.

The investigators also showed the Coup-TFII gene is essential to the process. The Coup-TFII protein binds to the promoter region of the Prox1 gene. The binding switches on production of the Prox1 protein that is required to create and maintain the lymphatic system.

The newer research builds on that earlier work from Oliver's laboratory. The latest study focused on the lymphovenous valves. These valves are found at just two locations in the body, on either side of the chest just under the clavicle bone where the lymphatic vessels intersect with the subclavian and internal jugular veins.

Working in mice, investigators discovered that these lymphovenous valves form from a newly identified subtype of endothelial cell found in developing veins. Like the LECs that form the lymphatic system, the newly identified endothelial cells make Prox1. But while the LECs leave the veins and migrate throughout the body, these endothelial cells stay put to form the lymphovenous valves.

Researchers demonstrated the process requires two copies of the Prox1 gene. That ensures adequate levels of the Coup-TFII-Prox1 complex and with it enough Prox1 to build and maintain the lymphatic system. Mice engineered to carry a single copy of Prox1 either did not survive or were born without lymphovenous and venous valves.

"If you have only one copy of Prox1 you are going to have a reduction in the Coup-TFII -- Prox1 complex and so a dramatic reduction in the number of cells available to build the lymphatic system. That explains the defects we see," Srinivasan said.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. R. S. Srinivasan, G. Oliver. Prox1 dosage controls the number of lymphatic endothelial cell progenitors and the formation of the lymphovenous valves. Genes & Development, 2011; 25 (20): 2187 DOI: 10.1101/gad.16974811

Cite This Page:

St. Jude Children's Research Hospital. "Story of lymphatic system expands to include chapter on valve formation." ScienceDaily. ScienceDaily, 15 November 2011. <www.sciencedaily.com/releases/2011/11/111114111720.htm>.
St. Jude Children's Research Hospital. (2011, November 15). Story of lymphatic system expands to include chapter on valve formation. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2011/11/111114111720.htm
St. Jude Children's Research Hospital. "Story of lymphatic system expands to include chapter on valve formation." ScienceDaily. www.sciencedaily.com/releases/2011/11/111114111720.htm (accessed July 24, 2014).

Share This




More Health & Medicine News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. Video provided by Newsy
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