Master Controller of Lymphatic System Development Found

Molecular biologists working with a line of genetically engineered mice have found that the Sox18 gene plays a critical role in the development and function of the lymphatic system.

Lymphatic vessels are required for maintaining fluid balance in the body and transporting infection-fighting white blood cells. Furthermore, the rate at which new lymphatic vessels can form is thought to be one of the key factors in determining how quickly a tumor can spread and thus how severely a patient will be affected by cancer.
Investigators at the University of Queensland (Australia) worked with a line of mice that had been genetically engineered to lack the Sox18 gene. They used molecular, cellular, and genetic assays to compare lymph development (lymphangiogenesis) in the modified mice as compared to normal animals.

They reported in the October 20, 2008, online edition of the journal Nature that Sox18 was expressed in a subset of cardinal vein cells that later coexpressed the Prox1 gene and migrated to form lymphatic vessels. Sox18 directly activated Prox1 transcription by binding to its proximal promoter. Overexpression of Sox18 in blood vascular endothelial cells induced them to express Prox1 and other lymphatic endothelial markers, while embryos lacking Sox18 showed a complete blockade of lymphatic endothelial cell differentiation from the cardinal vein.

"We suspected Sox18 might play a critical role in lymphatic vessel formation after observing that mice with one inactivated copy of the gene displayed similar symptoms to humans with a genetic condition that affects the lymphatic system, known as hypotrichosis-lymphedema-telangiectasia (HLT),” said senior author Dr. Peter Koopman, professor of molecular bioscience at the University of Queensland. "It turns out that Sox18 has a much more important role than we first thought – in fact, it is the master controller of lymphatic vessel development.”

"If we know how to prevent lymphatic vessels from forming, then we will be a lot closer to halting the spread of tumors through the body. Conversely, if we know how to stimulate the formation of these vessels, then it might be possible to treat diseases such as lymphedema,” Professor Koopman said.

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