New research animals earn their stripes
Friday, 30 June 2000
Fish are not the most intelligent animals, but Adelaide University geneticists are learning about the great mysteries of life from the brains of humble zebrafish.
Their studies are conducted at the ARC Special Research Centre for the Molecular Genetics of Development. There, Dr Michael Lardelli works with zebrafish, searching for genes expressed during the earliest stages of the brain's development, when its first cells are generated and the future brain is divided up into its various subregions.
"Zebrafish combine some of the best characteristics of those other two workhorses of developmental genetics, the mouse and the vinegar fly ", said Dr Lardelli. "Having worked with both mice and flies, it was love at first sight when I saw a developing zebrafish embryo,"
The zebrafish (Danio rerio) is a small freshwater fish about 3 cm long that gets its name from prominent black and white stripes running along its body. Originating in India, the fish are now widely distributed across the world.
Zebrafish have been studied by developmental researchers for more than 30 years, and they even have their own website <http://zfish.uoregon.edu/> where many details of their biology are revealed. They are small and tolerate high densities, so they are inexpensive to keep and breed in large numbers. They have a short generation time and a single female can produce more than 200 eggs in a week.
Once they are fertilised, zebrafish eggs develop externally, rather than in a womb as mice do. The developing embryos are completely transparent, so they are easily studied under a microscope, where every cell can be seen. The eggs develop quickly; from fertilisation to hatching takes only 3 days.
"A zebrafish embryo does in three days what takes a human three months!", said Dr Lardelli.
Under the microscope, the developing eggs can be filmed, exposed to chemicals in the water that bathes them, or even to surgical procedures, and their progress compared with other untreated eggs at the same stage of development. Parts of embryos can be marked with fluorescent dyes to determine their fate as the embryo increases in complexity. New genes (transgenes) can be injected into the embryos to see their effect on development.
Zebrafish can also be studied by mutating the embryo's own genes and observing what effect this has on development. Such studies are revealing how nerve cells develop in the brain and nervous system, and which genes control the development of the backbone.
These and other advantages mean that zebrafish are replacing laboratory mice for many genetic studies. "Growth in interest in zebrafish has been exponential over the past few years,' said Dr Lardelli. "As the usefulness of this system increases, we may see a greater proportion of articles in developmental journals describing zebrafish research, while mice are used more to address questions specific to mammals," he said.
"Our search for genes controlling brain development has been more successful that we had hoped, " said Dr Lardelli. "We have found more genes than we have the capacity to analyse in detail, so we are forced to focus on a few of the most interesting ones, and put the rest aside," he said. "Still, it's better to have too many than too few."
The understanding of the genetics of zebrafish is now so advanced, that scientists believe the entire zebrafish genome will be sequenced by the end of 2001. While that will mean that they know a great deal about the development of zebrafish, the real benefits of the study will lie in their wider implications.
Knowing how the brain develops, even in a lowly vertebrate such as a fish, will greatly help our understanding of diseases such as Parkinson's disease, spina bifida, Alzheimers disease and other afflictions of humans that have an inherited component or which are the result of incomplete embryonic development.
The scientific discoveries are likely to lead to many health benefits which, in turn, will open up huge commercial possibilities. "There is big money being invested by pharmaceutical companies in the genetic research done on zebrafish," said Dr Lardelli. "The intensity and competitiveness of the research is very exciting, but the zebrafish community still retains a friendly, co-operative attitude," he said. "Let's hope that it continues that way."
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