Zebrafish emerging as a research model

Zebrafish (Danio rerio) is a tiny, tropical freshwater fish that is native to River Ganges. In recent decades, it is gaining popularity in biological research as a model organism owing to its diverse potentials. Recent investigations on this fish have unfolded vital genetic mechanisms involved in vertebrate development, tissue and organ regeneration, and gene function and
regulation in human diseases. Consequently, the demand for this model is increasing in experimental research.

Widely studied

However, this was not always the case. For many years, zebrafish was an aquarium pet and was rarely in use as lab model. It started attaining the status of an experimental model when two genetic screens developed by Christiane Nüsslein-Volhard and Wolfgang Driever proved that this fish was a promising model for gene-knock-down and gene-over-expression protocols. Since then, the popularity of zebrafish expanded exponentially in research work and presently, this fish is considered as the ‘ultimate system’ to resolve biological questions that have remained unanswered using other conventional models like frogs.

But why zebrafish? A number of features make it an ideal organism for laboratory experimentation. These include its small size (2.5 – 4.0 cm) and slender body (0.8 – 1.2 g), and short generation time. An adult zebrafish lives for a maximum of 5.5 years in captivity (laboratory) and 3.5 years in nature on an average.

In biology, it is essential to estimate the extent of similarity in gene structure and genome of an organism with that of humans to be considered as model organism in the study of human genetics or disease. The scientists of the Wellcome Trust Sanger Institute, UK have come out with a complete sequence of zebrafish genome that comprises 1.3x 10 billion base pairs representing more than 26,206 protein-coding genes. The genome of this fish embodies more than 70% human gene orthologues. Signalling pathways of both zebrafish and humans have overlapping genomic consensus. Thus, fully sequenced zebrafish genome is not only serving as a reference tool for genetic regulation of development, but also enabling researchers to understand the evolution of vertebrate gene function as a whole.

Zebrafish is occupying a prominent position in biomedical research for identifying genes, dissecting genetic pathways and their regulation in a wide range of human diseases. Because of neuroanatomical, neuroendocrine, neurochemical and genetic homology to mammals, chemical genetic screens of zebrafish is an ideal experimental model in understanding neurological disorders such as depression, anxiety, autism, Alzheimer and Parkinson diseases.

The fish is proving to be promising in the investigations pertaining to muscle dystrophy and regeneration, and renal and gastrointestinal disorders among others. Recent research has revealed that this fish is capable of repairing and regenerating heart muscles. So, if it is possible to find and activate the similar genes responsible for the repair of damaged cardiac muscles in humans, it may prove to be promising in optimising remedial measures for myocardial infarction. Another important area where this model seems pertinent is cancer biology. It can help in deciphering oncogenes, their expression profile, regulatory mechanisms involved in tumorigenesis, tumour growth, angiogenesis and progression of metastasis.

The expansion of utility of zebrafish as research model during the last few decades has lead to emergence of a community of zebrafish researchers and the establishment of global research associations where researchers discuss the latest advancements in zebrafish research. As the field grew, conferences dedicated to zebrafish research came into existence. Of the many, the two largest ones that are held are the International Zebrafish Conference, an biennial conference organised in USA, and the European Zebrafish Meeting, a conference that is held in one of the European countries, in the years alternate to that of International Zebrafish Conference. Closer home, the Indian Zebrafish Investigator’s Meeting (iZIM) has been taking place every year since 2015. A recent review on zebrafish research in India reveals that there are more than 30 active research groups working and contributing to research on zebrafish as research model.

Currently, biologists are confident that this fish indeed is an asset in resolving biological problems. The tremendous optimism that has developed in scientific community has inspired them to refer this fish as ‘Molecular Swiss Army Knife’. Nancy Hopkins of Massachusetts Institute of Technology, USA, goes a step further and remarks overwhelmingly, “This is not a mere fish, it’s a little human with fins.”

(The author is a faculty at Karnatak University, Dharwad)