A Fishy Tale
Why scientists find fish so fascinating
In the basement of the Biological Sciences Research Building, behind the heavy metal door with the combination lock, it’s always a tropical 82 degrees. The rooms are filled from floor to ceiling with racks of clear plastic tanks. The only sound is the quiet bubbling of oxygen through water.
At first, the tanks appear to be empty, but move closer and you’ll see quick flashes of silver as hundreds of inch-long striped fish dart around. These are zebrafish — more formally known as Danio rerio.
Native to streams and marshes of India, Pakistan and Southeast Asia, they were originally imported for aquariums. Now they have a new home in biomedical research laboratories worldwide.
According to the U-M’s animal census, there were nearly 24,000 zebrafish on campus in 2009. Over the last two decades, the U-M’s fish population has grown as more scientists switch some, or all, of their research from mice to fish. Zebrafish have special advantages that make them particularly valuable for biomedical research.
- It takes 19-20 days for a female mouse to produce a litter, but a female zebrafish can lay hundreds of eggs that turn into embryos just one to two days after fertilization.
- Zebrafish embryos are transparent and develop outside the mother’s body, so it’s easy to see internal organs as they develop.
- There’s no need to inject zebrafish with experimental drugs. Just add the drug to tank water and the fish will quickly absorb or swallow it.
- Even a small lab can afford its own fish colony and most scientists are happy to donate “starter” fish to colleagues.
- Fish are vertebrates with a backbone and all vertebrates evolved from a common ancestor, so zebrafish and people have a lot in common. Both progress as embryos through the same developmental stages and share similar genes.
Daniel Goldman, Ph.D., a neuroscientist, professor of biological chemistry and research professor in the Molecular & Behavioral Neuroscience Institute, studies genes and signaling pathways that control development of the central nervous system, especially the optic nerve and retina. He was one of the first Medical School scientists to be hooked by zebrafish.
One thing Goldman finds fascinating about zebrafish is their ability to regenerate damaged organs. If you injure the retina of a mouse, the cells die and the mouse goes blind. Injure the retina of a zebrafish and the fish will just grow a new one.
“No one knows why zebrafish retained the ability to regenerate organs or why mammals lost that ability,” says Goldman. “We know that zebrafish have the same retinal cells as mammals, and the genes that regulate regeneration in fish are still present in mammals.” Understanding how regeneration works in zebrafish could be the first step toward finding a way to restore vision in people with damaged retinas.
Goldman has persuaded many U-M scientists to become fish enthusiasts. James Dowling, M.D., Ph.D., assistant professor of pediatrics and communicable diseases and of neurology, is one of them. “I started with 10 fish that Dan gave me,” says Dowling.
Dowling uses zebrafish for research on myotubular myopathy and Duchenne muscular dystrophy. For Dowling, the big advantage of working with fish is that they are almost all muscle. And it’s easy to identify fish with defective muscle tissue.
“Fish have to swim to live; they get their oxygen and food by moving around,” Dowling explains. “Fish that can’t swim normally don’t live more than a couple weeks. Mice, on the other hand, can have a lot of muscle weakness and it doesn’t trouble them that much.”
Mark W. Russell, M.D. (Fellowship 1996), the Aaron Stern Professor of Pediatric Cardiology, uses zebrafish to study a protein called obscurin that organizes and supports skeletal and cardiac muscle fibers as muscle develops in an embryo. “Zebrafish are an excellent model of muscle growth and development,” he says. “Access to the embryos allows you to take cells from one fish and put them in another. You can add or remove genes and then watch the embryos develop to see what happens.”
It may seem like a long way from fish tank to clinic, but U-M scientists say it could be closer than you think. They believe zebrafish have the potential to accelerate the pace of biomedical research and bring about faster, better treatments for human diseases. That makes little Danio rerio a very big fish on campus. —Sally Pobojewski
A Fishy Tale
Other U-M scientists using zebrafish for research