Is the zebra fish leading us to new therapies?

A little over a year ago, the Flanders Interuniversity Institute for Biotechnology (VIB), the D. Collen Research Foundation, and the Catholic University of Leuven invested in the acquisition of a new technology provided by the zebra fish. This small aquarium fish can be used to aid the study of the function of human genes. That this investment is reaping returns is evident from the study that VIB researchers at the Catholic University of Leuven are publishing today in the renowned journal Nature. They have shown for the first time that new blood vessels do not grow in random directions, but that they are guided by specific signal molecules. This is a major step in the development of new targeted forms of therapeutic angiogenesis.

A complex network

Blood vessels transport blood throughout our body. They form a kind of network to bring the necessary nutritional and building materials to organs and tissues and to carry off waste products. So, it is difficult to overstate the importance of blood vessels to a well-functioning body. Disorders in which the blood supply is impaired are quite serious: deficient blood supply to the heart, for example, leads to heart attack. Medical science hopes to be able to treat such diseases in the future by stimulating the growth of new blood vessels, a form of therapy called therapeutic angiogenesis.

Despite ever-growing knowledge about blood vessel formation (angiogenesis), scientists still know little about how the new blood vessels choose their path to reach a particular organ or tissue. Discovering these mechanisms would greatly aid development of new strategies for therapeutic angiogenesis. Not only must the growth of new blood vessels be stimulated, but the blood vessels must also be oriented specifically within an organized and coordinated network.

Daring hypothesis

Our nerve-tissue is also constructed as a very well-organized and coordinated network. It is known that, during their growth, nerves orient themselves very specifically toward a target organ or tissue. Then, by means of attraction and repulsion signals, so-called signal molecules guide the nerve cells to their target. In their search for the mechanisms behind the targeted growth of blood vessels, Monica Autiero and her co-researchers under the direction of Peter Carmeliet (VIB, Catholic University of Leuven) asked themselves whether blood vessels might perhaps use the same signals as nerve cells.

To answer this question, the researchers called on the small, translucid zebra fish. The great advantages of using zebra fish instead of mice are that zebra fish grow and multiply very rapidly and – because you can see through them – scientists can study the development of their blood vessels under the microscope.

Blood vessel guides

In collaboration with American and French scientists, the Flemish research team corroborated the bold hypothesis. Focusing their research on UNC5B, a signal molecule receptor for nerve cells, the researchers demonstrated that zebra fish that are unable to produce UNC5B construct a blood vessel network with uncontrolled branches and divergent patterns. This indicates that the receptor and the signal molecule are of crucial importance in guiding new blood vessels.

Scientists can now predict with great certainty that nerves and blood vessels use the same ’guides’ along their routes to their targets. A finding that is very important for the development of new, targeted forms of therapeutic angiogenesis.