History of the Zebrafish Model

Zebrafish have only been used as a model organism by a lot of labs in the last 15 years or so. In the 1970s, George Streisinger, a scientist at the University of Oregon, was interested in using a vertebrate model organism that was simpler than the mouse and easy to manipulate genetically.

As a tropical fish enthusiast, he chose the zebrafish, which is commonly found in pet shops and home aquaria. Streisinger’s colleagues in Oregon, amongst them Chuck Kimmel, were impressed with the ease of using the fish and for Kimmel the embryo was particularly attractive for studying nervous system development.

Since the mid 1990s, many more scientists have started using zebrafish as a model organism to study developmental biology. Currently there are at least 600 laboratories around the world that use zebrafish.

The big screens

A big step forward in the zebrafish field came when two large genetic searches for mutants were carried out in the early 1990s. One was led by Nobel prize winner Christiane Nüsslein-Volhard in Tübingen, Germany, and the other by Wolfgang Driever and Mark Fishman in Boston, USA. The identification of mutants is one of the most important strategies for the study of many areas of biology.

A mutation often provides the first insight into the role of the gene in normal development or in a healthy individual.

The screens looked at thousands of families of fish to find mutations that affected early development. In the end around 4000 mutants were identified, and the results were published in a single, mammoth issue of the journal Development in December 1996.

Scientists have spent many years since then working with the mutants that came out of the screens. And many more screens have been carried out in individual labs since then.

However, finding a mutant is just the first part of the story: you can see the effect of the mutation on the zebrafish embryo, but you do not know what gene is affected.

Sequencing the genome

Zebrafish researchers needed more genetic resources in order to understand and characterise the mutants further. The community got together to initiate the sequencing of the whole zebrafish genome, which began in 2001 at the Wellcome Trust Sanger Institute in Cambridge.

To date over 14,000 genes have been described in the zebrafish genome, and although sequencing is not fully complete, we have a working draft that has proved immensely useful to scientists around the world.

More information is available at the Wellcome Trust Sanger Institute: Zebrafish Genome Project resources webpage.