The zebrafish should be known to many aquarium enthusiasts mainly because of its striking pigmentation. However, the characteristic black-blue stripes, to which the animal owes its name, only form over time. Its eyelash-sized larvae, on the other hand, are still more or less transparent. Many developmental processes in their bodies can therefore be observed under the light microscope. For this reason, they now serve as a model organism for research groups around the globe.
"At the University of Bonn, for example, we are investigating how zebrafish repair defective nerve tissue," explains Prof. Dr. Benjamin Odermatt from the Institute of Anatomy at the University Hospital Bonn. "We are also interested in this because many genes involved in this process also exist in a similar form in humans." In principle, agents that boost these repair genes in fish could thus also work in humans. However, the differences between the genetic makeup of fish and humans are often significant. The larvae are therefore sometimes of limited use in the search for new drugs.
Fish gene replaced by human gene
"We therefore took a different approach," explains Prof. Dr. Evi Kostenis from the Institute of Pharmaceutical Biology at the University of Bonn. " For a human gene known to play a role in the repair of nerve cells we looked for its counterpart in zebrafish. Then we excised this counterpart in the fish and replaced it with the human version." The new genetic material took over the function of the original zebrafish gene. "If we now find a substance that boosts the repair processes in the fish with the human gene, there is a good chance that this will also be the case in humans," says the scientist, who is also a member of the Transdisciplinary Research Area "Life and Health" at the University of Bonn.
The researchers demonstrated that this replacement works in their pilot study on the so-called GPR17 receptor. In humans, its overactivation can lead to diseases such as multiple sclerosis (MS). Nerve cells communicate by means of electrical signals. Their extensions are surrounded by a kind of insulating layer, a lipid-like substance called myelin. It prevents short circuits and also significantly speeds up the transmission of stimuli. This protective sheath is produced by specialized cells named oligodendrocytes. These resemble a microscopic octopus: many long arms extend from their cell body, most of which consist of myelin. Like an insulating tape, these wrap themselves around the nerve cell processes during brain development. Normally, the protective layer lasts a lifetime. [...]