Zebrafish are a powerful model for studying how organs form and what goes wrong in early development, because embryos develop outside the mother and can be observed and gently manipulated. This, and their previously mentioned genome mapping in 2013, makes zebrafish particularly useful for investigating rare genetic developmental disorders, where identifying the responsible gene and its effects is the first step towards better diagnosis and, eventually, targeted treatment.

For instance, in a study at Augusta University, Georgia, USA (then the Georgia Health Sciences University), scientists were able to confirm that the PHF21A gene was involved in head and brain abnormalities in the rare disorder Potocki-Shaffer syndrome, which affects the development of several tissues, by deactivating the gene in zebrafish.

Zebrafish brains share many core features with other vertebrates, and researchers can track brain activity and brain development with advanced imaging approaches. This makes zebrafish useful for studying how neural circuits form and how they influence behaviour such as learning, stress responses and social interactions.

When it comes to conditions related to the brain, zebrafish have been used not only to improve our understanding of neurological conditions, such as motor neurone disease (MND) and multiple sclerosis (see this University of Edinburgh, UK, study), but also behaviour. This is because the zebrafish brain and nervous system can be studied at the level of nerve cells, in both healthy and diseased tissue, to reveal new information about how these conditions work and, in turn, can be treated.

Forms of MND, such as amyotrophic lateral sclerosis (ALS), currently lack a cure, and symptoms tend to get progressively worse as the motor neurons in the brain and spinal cord die. A non-invasive study using zebrafish at the Institut National de la Recherche Scientifique, Canada, revealed the differences in the neural system between healthy and diseased zebrafish with ALS-like symptoms, to help understand how ALS develops.

Zebrafish can also accurately mimic strokes, for example in the research by the University of Manchester, UK, which developed an improved way to study haemorrhagic stroke (brain bleeding that kills brain cells) that closely resembles the condition in humans. (brain bleeding that kills brain cells) that closely resembles the condition in humans. 

Because zebrafish show similarities with humans in how they behave, such as in terms of social behaviour, they can be very useful in the understanding of learning, cognition and brain function, as well as conditions related to these factors, such as stress and anxiety.

Zebrafish also have several of the same brain chemicals to humans — those that control behaviour — including oxytocin, which is involved in emotions like love and fear. 

In a study at EARA member the Max Planck Institute for Biological Intelligence, for instance, researchers were able to selectively breed zebrafish to uncover distinct personality traits and brain activity differences associated with human psychiatric conditions. 

Meanwhile, scientists at Harvard University, Massachusetts, USA, gained surprising new insights into behaviour during feeding by studying zebrafish larvae.

Larvae have also revealed how social experiences can impact behaviour at an early stage, in research by EARA member the Champalimaud Foundation, Portugal, to potentially shape behaviour into adulthood.

Zebrafish can develop similar cancers to humans, such as skin cancer, with tumours that can resemble those found in cancer patients. One of the ways to do this is through a xenograft – where tissue from one species (in this case, humans) is grafted or implanted into a zebrafish (an avatar) even though the zebrafish will not have this cancer naturally. These cancer avatars can then provide evidence about how well a particular drug, or chemotherapy, may work in the clinic, without the unknown risk of testing it on people. 

The clear bodies of zebrafish larvae can allow for more precise imaging techniques to be developed, or for live tracking inside the body, such as to monitor the development of tumours, or the passage of toxins and their resulting effect.  

Some of the main advantages to using zebrafish in general – namely, a fully sequenced genome that shares many genes with humans, and transparent embryos – also means that scientists can search for genes within the zebrafish genome that are linked to human cancer, and precisely visualise cancer growth at the level of single cells. This also applies to drug discovery by testing small molecules for their response to treatment, or toxicity, such as the study at the zebrafish core facility of the Karolinska Institute, in Sweden.

Recently, researchers at the Children’s Hospital Los Angeles, USA, were also able to reliably study the aggressive childhood bone cancer Ewing sarcoma by using zebrafish, to shed light on how the tumours grow and interact with other cells and molecules in the body.  

Conditions affecting the metabolism (the chemical reactions that provide energy in organisms) such as obesity and diabetes, are among the most prevalent – and growing – global health conditions today. As zebrafish are similar to humans in several key aspects related to metabolism, such as the biology of fat cells and tissue, they can be used to study these types of disease to understand the effects of genetic and environmental factors, or to identify new targets for treatments.

At the Karolinksa Institute, Sweden, researchers found a molecule that can stimulate the formation of cells that produce insulin – a crucial hormone needed to manage type 1 diabetes – to lower blood sugar levels in zebrafish. While another team, at the University of Sheffield, UK, developed a method to observe how the brain regulates blood supply in zebrafish, which not only led to the discovery of a drug that can reverse the effect of high glucose in diabetes on the brain, but also new insights into Alzheimer’s disease.

Zebrafish can regenerate many of their organs and body parts, including the heart, nervous system, eyes and fins and they could hold the key to understanding how regeneration could also be achieved for people with permanent injuries, such as from accidents, or lasting damage caused by conditions like cardiovascular disease and diabetes. 
A team at the Weizmann Institute of Science, Israel, has looked at the healing powers of zebrafish to understand how they are able to regenerate their heart. Another group of researchers from Caltech, US, identified that heart cells derived from early development cells - neural crest cells - orchestrate this process of regeneration and are now investigating how to reactivate these genes in humans.  
A group led by Imperial College London, UK, has identified a vital mechanism in zebrafish embryos that regulates heart valve development. The described pathway, involving calcium ions and ATP, is crucial for heart valve development and could inform future prevention and treatment of congenital heart valve defects and diseases.  
Meanwhile, a study at Ludwig Maximillian University (LMU), Germany, used zebrafish to understand how to prevent the formation of scars in the brain that result from brain injury.  

Zebrafish are widely used to study immunity because researchers can observe immune cells moving through the body and responding to infection in living animals. In 2023, researchers at the University of Wisconsin–Madison, US, visualised zebrafish T cells in unprecedented detail and linked this to how adaptive immunity is organised in fish. More recently, researchers at the EARA member Université Libre de Bruxelles (ULB), Belgium, are also mapping immune cell diversity in the zebrafish brain, supporting its use in neuro-immune research relevant to neurological disease and making this map a resource for the entire zebrafish community.  
Zebrafish have also provided important insights into diseases caused by infections, such as tuberculosis – a group at Leiden University, Netherlands, identified how the bacteria can be cleared most efficiently from the lungs of zebrafish by looking at the movement of specific immune cells.  

Read about zebrafish in nanomedicine studies in this Medical News article, which summarises the advantages of using these animals and highlights their value in investigating nanomedicines.  
Zebrafish have also proven to be an ideal organism to use to improve and refine new scientific techniques — an example is imaging the body using microscopy and other methods. Although transparent when younger, zebrafish become more opaque as adults, but researchers have worked to overcome this, for example at Cornell University, New York, USA, which developed techniques to allow the networks of whole adult zebrafish brains to be visualised to better study brain disorders.  
​Meanwhile, a study at the Swiss Federal Institute of Technology in Lausanne (EPFL), Switzerland, tested a microsurgeon robot on zebrafish embryos to demonstrate that the tool could successfully target specific areas of tissue to look at how a body grows.  
Zebrafish can even help to understand how spaceflight affects humans. In research by Queen’s University Belfast, UK, zebrafish in a hibernation state were found to experience fewer effects from radiation, bolstering our knowledge of how humans may safely travel to Mars.