Everything you always wanted to know about Zebrafish but were afraid to ask.

What about Zebrafish?

Zebrafish (Danio rerio) is a small tropical freshwater fish, native to the streams of the southeastern Himalayan region that commonly inhabits slow-moving water bodies. It takes his name from the horizontal blue-pigmented stripes aligning his body, which are reminiscent of the zebra stripes. Danio rerio adults grow up to 4 cm and their lifespan is between two to three years in standard laboratory conditions. Both size and age can be larger in their natural habitat.

Zebrafish are omnivorous, primarily eating zooplankton and insects, although they can eat a variety of other foods, such as worms, small crustaceans or algae. This is one of the reasons that make this freshwater fish an extremelly robust animal model.

The approximate sexual maturity time for them is three months. A male must be present to induce female ovulation and egg fecundation. Females are able to spawn at intervals of two to three days, laying more than two hundred eggs in each mating. This vast progeny is another advantage for using this particular family of fishes.

Upon eggs release, embryonic development begins. The zebrafish embryo develops quickly, with precursors to all major organs appearing within 36 hours post fertilization (hpf). The embryo begins as a yolk with a single enormous cell on top, which divides into two and continues dividing until there are thousands of small cells. The cells then migrate down the sides of the yolk and begin forming a head and tail, which later grows and separates from the body. From 4 dpf, heart physiology is stable; from 5 dpf they respond to optical, touch and acoustic stimuli and display free swimming, which sugest a mature nervous system; also from 5 days the digestive/excretory system is fully functional. Interestingly, zebrafish embryonic and larval tissues are optically transparent, what allows to vizualise morphogenetic movements and organs in vivo (i.e.: Heart beating). Thus, fast life cycle and transparency are additional features making this species a powerful animal model for biomedicine.

Zebrafish larvae

Zebrafish (Danio Rerio) larvae

All the named advantages have allowed zebrafish to become an important tool for high-throughput screenings of small molecules with therapeutic effects. In that sense, both academy and pharmaceutical industry use zebrafish to save time and money in preclinical studies for assessing toxicity and efficacy of new drugs, in the fields of infection, cardiovascular diseases, neural disorders or cancer. In summary, the advantages of using an animal model such as zebrafish for biomedicine and drug discovery are multiple:

i) Drugs are administered directly in their swimming water. This feature has two main advantages, it saves time in the procedure, if compared for example with the time invested in injecting drugs in mice; and it helps to understand how a molecule behaves in terms of ADME - Absorption, Distribution, Metabolism and Excretion - when confronted to a whole living animal versus its behavior in a biochemical or cell culture drug screening, which by nature will give a much limited information in that regard.

ii) The small size and high number of the zebrafish progeny allows the parallel and reproducible testing of several drugs and dosages in simple multiwell plates.

iii) Zebrafish share a high degree of conservation with humans in both their genome and their physiological processes (close to 80%), which permit to asses with certainty the possible toxicity or effects that a drug could have when administered to us.

iv) Transparency in Danio rerio larval stage, combined with a growing battery of fluorescent tissue-specific zebrafish transgenic lines, plus novel advances in imaging capture and processing allows to analyze in vivo the effects of drugs in groups of cells or single tissues.

All these features have allowed the use of zebrafish to yield advances in the fields of developmental biology, oncology, toxicology, reproductive studies, teratology, genetics, neurobiology, environmental sciences, stem cell research and regenerative medicine, and evolutionary theory… and this is only the beginning!