Time to grow up. Blood vessels (red) direct islets (green) to differentiate.

The Green Light for Organ Development

Blood vessels are the body's plumbing, supplying food and oxygen and removing waste. Now two papers published online this week by Science show that blood vessels play a more active role than previously believed: Even before they start to function, blood vessels help the liver and pancreas develop.

In 1995, cancer researchers found the first evidence that there's more to blood vessels than meets the eye. They reported that endothelial cells, which make up blood vessel walls, produce growth factors, indicating they may play some role in development.

The new studies build on that work. The first team, led by Douglas Melton of Harvard, began scrutinizing blood vessels after noticing that the endoderm--embryonic tissue fated to become the pancreas and other organs--touches a major blood vessel, the dorsal aorta. Because the developed pancreas monitors blood vessels, measuring glucose levels and producing insulin accordingly, the researchers wondered whether the pancreas and dorsal aorta also communicated during development. To test this, they performed experiments such as growing mouse endoderm in culture with and without embryonic dorsal aortae. Only alongside the blood vessel did the tissue produce pancreas-specific markers, including insulin.

The second group, led by Kenneth Zaret of the Fox Chase Cancer Center in Philadelphia, took a different approach. They examined how mouse livers develop when a gene called flk-1, which encodes a receptor for VEGF, is mutated so that no endothelial cells develop in the liver. When they grew these liver cells in petri dishes, the flk-1 culture grew to the same size as the normal culture but contained far less liver tissue, growing connective tissue instead. Surprisingly, the endothelial cells' influence arose well before the cells fully formed into vessels, suggesting that the cells themselves--and not some component of the blood--are sending the growth signal.

Understanding how cells define themselves in an embryo is critical to designing stem-cell-based treatments for disease. "If we're going to induce organs to form, we have to have a thorough understanding of how the embryo develops them," says organ replacement biologist Michael Longaker of Stanford University School of Medicine in Palo Alto, California. "We will never do it in a more elegant way than the embryo."

Related sites

Melton lab home page
Zaret lab home page

Posted in Biology