Model Organism Week: Research’s Next Top Model

Only in the past three decades has Danio Rerio (Zebrafish) started to call the lab their home. Since then, they have helped in finding cures for cancer, understanding more about embryological (vertebrate) development, and vertebrate behavior. One lucky zebrafish has also gone where few humans have been: space. On June 22nd 1976 the space station Salyut 5 was launched, with one of the crew members being a zebra danio.

Here on earth, zebrafish were pioneered as a model organism by Dr. George Streisinger, a molecular biologist at the University of Oregon who produced the first zebrafish clone.

The early career of the zebrafish

At first, zebrafish were increasingly used by developmental biologists. Thanks to their transparent embryo, scientists can visualize developmental processes under the microscope. Similarly, experiments that aim to disrupt some aspect of embryological development to investigate molecular processes are easily conducted with zebrafish.

The zebrafish embryo develops from fertilized egg to larva in about three days, combined with the few hundred eggs that can be obtained from a single spawning, the zebrafish is not only a prolific subject but also one that provides the possibility of studying developmental processes in a short period of time. As a graduate student, less time is required per experiment, which means a higher turnover rate and productivity. Of course, this is mostly applicable to developmental biologists. Behavioral neuroscientists study the organisms after it hatches and single studies can take a few months to complete.

Fishy Behavior: studying brain function through behavior

The zebrafish may have started out as a favorite among developmental biologists, but it is becoming ever more popular in the behavior genetics, and behavioral neuroscience labs. Zebrafish are a highly social species and form shoals (group aggregation), they also exhibit a rich repertoire of characteristic behaviors that can be exploited in experiments. There are many ways to study the brain, and brain function, but for behavioral scientists the study of the brain doesn’t always have to be invasive and can be modeled in relatively simple organisms. The zebrafish, being a vertebrate, gives us the added advantage that a large number of genes are conserved among other vertebrate species, including humans. Thus, studying zebrafish behavior in response to a drug or compound can give us a better understanding of what the drug effects might be on humans as well.

Pretty much any compound or drug with hydrophilic characteristics, and which consequently can be dissolved in water, can easily be administered to zebrafish. Simply dissolving the drug or compound in the tank water in which the zebrafish is present, will lead to absorption through the gills of the fish. Studies have shown that, for example, alcohol concentrations in the brain reach an equilibrium with the environmental concentration in about an hour of exposure [reviewed in 1].

Behavior is still an area that is not well understood, even though a large number of human conditions have behavioral symptoms (think autism, alcoholism, depression, anxiety disorders). Zebrafish are an excellent model to study some behaviors characteristic of certain conditions, such as anxiety, fear, aggression, and social behavior [2].

Plunging into zebrafish research

Taking the plunge on zebrafish research doesn’t have to take a large investment. This makes starting out with zebrafish in the lab accessible and feasible on modest budgets. Of course maintaining a large facility with thousands of zebrafish does come with a certain cost, and an initial investment in professional aquatic systems, but a small lab can start with a short trip to the pet store. A series of commercially available tanks and filters suffices to house a few hundred zebrafish, at least. Given that a study might require anywhere from 100-1000 zebrafish, it is doable to design projects with very little cost. The start-up expenses for a small facility using supplies from a pet store can run around a few hundred dollars. More elaborate and professional aquatic systems with automatic filtration and the possibility of housing a larger number of fish in a smaller space start in the tens of thousands of dollars in start up expenses. However, the maintenance costs after the initial expense is still very low, compared to mice and rats.

Why Zebrafish research is cool

First of all, zebrafish are a new kid on the bench, and therefore most projects you are interested in doing haven’t been done yet on zebrafish. The body of literature is growing faster and faster, but it does not come close, yet, to the knowledge we have of other model organisms. So here are some advantages to working with zebrafish

1. As a relatively new model, a lot of studies can be designed that have not been performed yet on this species. There is lots to do, and you never run out of ideas.
2. It is a vertebrate, and thus has a strong advantage in studies that benefit from a vertebrate system.
3. Small, easy to keep in large numbers.
4. Cheaper to keep in large numbers than mice and rats, enabling even medium sized labs to perform high throughput screening.
5. A number of genetic tools are available, and the zebrafish genome has been sequenced.
6. High fecundity allows for a lot of subjects to be generated, within a short generation time. Thus, as a graduate student there is hope of finishing a PhD within a reasonable amount of time.
7. Drug administration can be as simple as “add water” (and fish).

There are seemingly endless advantages to using zebrafish in biology, far more than I have summarized above. Having said that, zebrafish enthusiasts do also recognize the limitations of their favorite model organism. Generally speaking, no single model organism will ever be appropriate for all research studies, and the zebrafish can be seen as a very useful and promising tool that complements mice, rats, and fruit fly research.

1. One unavoidable disadvantage of a relatively new model organism is just that; it is new. A much smaller body of literature is available on the zebrafish compared to other model organisms.
2. Although a lot is known about the development of zebrafish, their behavior remains insufficiently studied. A number of labs are working hard to change this at this time.
3. Although zebrafish are a vertebrate, eggs develop outside of the body and although there are advantages to this for the purpose of observing embryonic development, there are limitations when studying vertebrate maternal behavior or aspects of in-utero development.

Zebrafish swimming into the future

With the expanding body of knowledge and the large number of tools available to study zebrafish, there is no doubt that this little organism will continue to make great strides in future research. As zebrafish are now being used in virtually all disciplines, from neurogenesis to oncogenesis, from behavior to genetics, its popularity is steadily increasing. The emergence of zebrafish conferences, and the increasing presence of zebrafish studies at large annual meetings such as the Society for Neuroscience, shows how zebrafish are increasingly becoming a model of choice.

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Christine is a PhD student at the University of Toronto. She studies drug-induced behavior, development of social behavior and neurochemistry. When she isn’t with her fish, she enjoys running, art, travel, and often finds herself behind her computer writing (sometimes, about zebrafish).

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[1] Gerlai, R., Lahav, M., Guo, S. & Rosenthal, A. Drinks like a fish: Zebrafish (Danio rerio) as a behavior genetic model to study alcohol effects. Pharmacol. Biochem. Behav. (2000) 67(4), 773–782.

[2] Sison, M., Cawker, J., Buske, C., & Gerlai, R. Fishing for genes influencing vertebrate behavior: zebrafish making headway. Lab Animal (2006) 35(5), 33-39.

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See other articles in the series:

Drosophila melanogaster- The fruit fly.

EEK! The Mouse.

Getting to Know Your Worms (C. elegans)

Saccharomyces cerevisiae a.k.a Budding/Baker’s/Brewer’s Yeast

The Almighty Fungi: The Revolutionary Neurospora crassa

We’re Gonna Need a Bigger Lab: Large Animal Models in Research

Tetrahymena: Little Creature, Big Discoveries

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