Why are Zebrafish so Cool for Scientists?

“Zebrafish” is the common name for the freshwater fish Danio rerio, a pretty animal about the size of a pen cap, with unique characteristics. This small species is originally from South Asia, where they like to live in slow-moving streams, shallow ponds, irrigation canals, and even rice fields. Maybe you have seen one of these little striped fish in an aquarium at home or at a friend’s house, as they are easy to keep as pets (Figure 1). However, in recent decades, they have also been widely used as laboratory animals, supporting experiments in biology and other sciences.

As a laboratory animal, zebrafish have numerous advantages. For example, each female can lay hundreds of eggs per reproduction cycle; the eggs develop into baby fish (embryos) very rapidly outside their mother; and the embryos are transparent, which makes it easy to follow their growth and development. When they are between 2 and 3 days old, the embryos start to swim around as they become larvae. It takes around 3 months (90 days) for them to turn into adult fish (Figure 2).

Another interesting fact about zebrafish is how similar our genetic backgrounds are to theirs. This means that the genes in zebrafish DNA closely resemble human genes. In fact, scientists discovered that 70% of zebrafish genes are shared with humans [1]. This means that a gene responsible for the zebrafish’s skin color, for instance, could be the same gene humans use to create skin color. This high similarity makes zebrafish an ideal model organism for studying diseases and novel treatments, as well as other important biological questions.

The Amazing Regenerating Zebrafish

Do you know Wolverine from the comics? He is one of the most well-known mutants, with a healing power that allows him to recover from even the most life-threatening of wounds. Imagine you had a superpower that allowed you to regrow a lost finger or a scraped knee overnight. Sounds like something out of a superhero movie, right? Well, the zebrafish, this tiny underwater superhero, can do it!

If zebrafish lose a part of their tail or fin, they can grow it back. When a zebrafish gets injured, its body immediately sends out an alarm that something is wrong, and it gets to work, fixing and rebuilding the lost part as if nothing happened. This process works not just for the fins, but also for the heart, brain, and other organs.

The process of growing back a body part that was lost or damaged is called regeneration. Humans can regenerate small things, like skin after a cut, but we cannot regrow big parts like arms or legs. This is why scientists are fascinated by zebrafish: their regeneration ability is like having a real-life guidebook for healing injuries. By understanding the mysteries of how zebrafish regrow their body parts, scientists hope to unlock the secrets of human healing. One day, we might be able to use what we learn from zebrafish to help people get better treatments for similar conditions involving injuries.

While the ability to regenerate is not present in higher vertebrates, such as humans or other mammals, it is a common feature among lower vertebrates, such as some fish with bony skeletons (like zebrafish) and amphibians that have tails, such as newts and salamanders [2]. For both animal groups, the research on regeneration started out by studying external appendages, such as tails and fins.

Although zebrafish fins are the most-studied structure in regenerative biology, remember these fish can also regrow other body parts. For example, a heart attack leaves a scar on a human heart forever. Yet, zebrafish can remove the scar and regenerate injured muscles. Thus, scientists are trying to figure out how this special power works, in hopes of advancing medical treatments for human heart patients.

How Does Zebrafish Regeneration Work?

Researchers often choose the caudal (tail) fin to investigate regeneration because it allows them to study the whole process clearly. It is also the largest zebrafish fin and thus easy to experiment on and observe compared to internal organs like the heart [3]. The caudal fin is also accessible at the larval stage, making it the earliest structure to study to understand tissue regeneration (Figure 3). Finally, the caudal fin can be cut without affecting zebrafish survival.

Tissue recovery has several stages, and specific types of cellular communication and certain genes are active at each stage. In zebrafish, a group of cells called the blastema is responsible for growing into a new structure just like the original one (Figure 3) [2, 4]. Imagine the blastema as a seed that grows and becomes a plant—in this comparison, the cells in the blastema of the injured organ multiply, forming a new body part.

The first stage starts immediately after the damage, when the body sends the alert that something is wrong. Inflammation is the body’s alarm system, indicating that there is a problem and protecting the body from attacking invaders, like bacteria. In about a day, a cap of skin forms to cover the injured area. It is important to cover the wound site to protect it and start the healing process, which begins about 1 day after the injury [5].

From 1 to 2 days post injury, the blastema forms and those seed-like cells multiply. These cells are like little builders that can turn into any type of cell needed to fix the injury. After the blastema is settled (from the second day after injury on), the regeneration process starts to rebuild the organ. New cells are created exactly where they are needed, like they have a blueprint for building a perfect new body part. Then, in a few days, voilà… the zebrafish has recovered and is as healthy as before the injury.

Take-Home Message

The zebrafish is amazing! This tiny, striped fish can regrow lost parts of its body, like its tail, fins, and even parts of its heart and brain! Scientists are fascinated by this ability and are studying zebrafish to uncover the secrets of regeneration. By learning how zebrafish heal so effectively, researchers hope to find ways to help humans recover from injuries and diseases and improve our overall health. Zebrafish are not just adorable pets; they are helping us unlock the mysteries of regeneration treatments.

Zebrafish regeneration involves a special group of cells called the blastema. The cells act like little seeds or builders to recreate lost body parts. Even cooler, zebrafish share many genes with humans, making them perfect for scientific research. By studying these cute fish, scientists are discovering how genes and cells work together to heal injuries. Next time you see a zebrafish, remember it is not just a beautiful aquarium fish—it is a real-life superhero helping scientists discover new ways to improve tissue recovery. They may be small, but they are making big waves in the world of science and medicine.

Glossary

Laboratory Animal: ↑ A small creature, like a mouse or fish, used in scientific research to help scientists safely learn about health, diseases, and new medicines.

Model Organism: ↑ A living being (animal, plant, or tiny organism) that scientists study to better understand how natural phenomena occur.

Regeneration: ↑ The ability of some animals to regrow lost or damaged body parts, like a zebrafish growing back its tail.

Blastema: ↑ A special mass of cells in animals that can regrow lost body parts (like a zebrafish’s tail or a salamander’s leg) by multiplication, creating new tissues and organs.

Inflammation: ↑ The body’s natural response to injury or infection, which cause redness, swelling, heat, or pain while the body works to heal itself.

Conflict of Interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

We thank the São Paulo Research Foundation (FAPESP) for the support, notably through the Center of Toxins, Immune Response and Cell Signaling - CeTICS (grants #2013/07467-1; #2019/27677-7) and its dissemination branch. GRD thanks National Council for Scientific and Technological Development (CNPq) for the support (grant # 446270/2024-5).

AI Tool Statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

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