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.
The study was supported in part by a grant from the National Institutes of Health and ALSAC.St. Jude Children’s Research Hospital
Summer Freeman | Newswise Science News
Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences