The zebrafish: the precious ally of researchers

In the aquatic animal facility, in the basement of the research institute, Sébastien Bedu, research engineer, uses a colander to collect eggs just laid by these small fish. Equipped with a needle, he injects a DNA fragment containing a gene whose function he seeks to determine. A manipulation “much easier to achieve than in mice for example, because it does not require surgery”he explains.

The zebrafish: an animal that fascinates researchers

Less known than the laboratory mouse, the zebrafish or “zebrafish” has become in recent years an important model organism for scientists, due to its physiological characteristics close to those of humans. Some 70% of human genes have an equivalent in the genome of this fish. And this is not its only asset: “It’s a small species, so we can raise a large number of them in small volumes of water,” says Sébastien Bedu, head of the animal facility. “When it reproduces, it lays a lot of eggs, it’s easy to handle, much less expensive than a rodent… it’s the dream model for the researcher!”he enthuses.

Also, if this fish got its name from the stripes it acquires as an adult, then in the early stages of its growth the fry is completely transparent, and some may even remain so afterwards. This transparency gives it a major advantage, allowing easy observation, with a simple microscope, of different biological phenomena within the whole organism.

“We can follow on this living animal the fate of the cells, their movement, their divisions, their death, without any invasive manipulation”, summarizes Laure Bally-Cuif, director of the Department of Developmental Biology and Stem Cells at the Institut Pasteur.

The Institute’s teams are particularly interested in the stem cells of the nervous system of this vertebrate. “Very rare in mammals, they are maintained in very large numbers in the adult brain of this fish”, explains the researcher, in the middle of rows of aquariums.

Real-time tracking

Essential to the plasticity of the brain through the neurons they generate, these cells can also be a source of pathologies when they function poorly. “By studying these cells, we hope to better understand their normal functioning and possibly find the mechanisms likely to correct them when they malfunction or activate them to produce more neurons”says Laure Bally-Cuif.

Other teams from the Institut Pasteur are also relying on the brain of zebrafish to decode the mechanisms involved in glioblastoma, a rare but very aggressive brain tumour, which remains without curative treatment to date. “What we are trying to find out is how to block the migration of cancer cells”, describes Sandrine Etienne-Manneville, head of the Cellular Polarity, Migration and Cancer Unit at the Institut Pasteur. “For that, we must first understand how they migrate”.

Here again, the zebrafish proves to be a perfect model. Scientists use tumor cells from patients with this cancer that they make fluorescent. They then inject them into the brain of the larvae, which are transparent, and whose blood vessels or neurons are colored by genetic manipulation. It then becomes possible to follow in real time the movement of cancerous cells inside the brain of fish.

“We can observe in vivo, within the brain tissue, whether these cells have significant invasive properties and how and where they migrate, which will improve the diagnosis in patients with this cancer”, hopes Sandrine Etienne-Manneville. Another interest of zebrafish: “we can test many molecules at home, which we add to our swimming water, to see whether or not they influence the invasion of the tumor”continues the researcher.

The objective is of course to one day develop a treatment for this tumour, which represents the second largest pediatric cancer in France and the leading cause of death due to cancer in children.