Key protein controlling blood vessel growth in mice’s brain identified

WASHINGTON - A new study has suggested that one protein single-handedly controls the growth of blood vessels into the developing brains of mice embryos.

Stanford University researchers said that understanding how the protein, a cellular receptor, functions could help battle brain tumours and stroke by choking off or supplementing vital blood-vessel development, and may enhance the delivery of drugs across the blood-brain barrier.

“The strength and specificity of this receptor’s effects indicate that it could be a very important target,” said Calvin Kuo, senior author of the research.

“It’s really a spectacular phenotype. For a stroke, we might want to stimulate the function of this receptor; for a brain tumor, we might want to inhibit it,” said Kuo.

The protein, called GPR124, is a member of a family of proteins called G-protein-coupled receptors that span the cellular membrane.

The researchers began by looking to see where in an adult mouse the receptor was normally expressed.

They discovered that it is found almost exclusively on the endothelial cells of the brain and the central nervous system. (Endothelial cells line blood vessels throughout the body and help blood to flow more smoothly.)

When the researchers bred mice lacking the ability to express GPR124, they died as embryos after about 15 days of gestation.

“These embryos did not have any blood vessels entering their forebrains or developing spinal cords at all. And the effects were very specific for the nervous system since all other organs had normal blood vessel development,” said Kuo.

In contrast, control mice embryos, with normal expression of GPR124, began developing brain blood vessels by about 11.5 days.

Interestingly, the researchers noticed that the timing of vessel development coincided with the formation of a physiological security checkpoint called the blood-brain barrier.

Kuo and Kuhnert next overexpressed GPR124 in the mice and followed their development. While the mice at first seemed normal, they began to develop large tangles of blood vessels in their forebrains as they aged.

After about one year, nearly 70 percent of the mice displayed this kind of abnormal hypervasculature - but only in their brains.

The results showed that the action of GPR124 is highly specific for the central nervous system.

The findings were published in the journal Science. (ANI)