Introductory Chapter: The Zebrafish Model is Pushing Science Forward

1. Introduction

The use of Danio rerio (zebrafish) in science has a long track. It started in the 1970s and early 1980s, driven mainly by George Streisinger’s (1927–1984) work. Streisinger was the founding father of zebrafish research while based at the University of Oregon, where he established a zebrafish research colony and developed the first practices for mutagenesis and mutation screening, aiming to study the development of the nervous system through molecular analysis. His fish clones stood among the primary successful vertebrate clones generated; altogether, those were the first steps that led to many novel applications around the globe. Interestingly, zebrafish had such a notorious impact on science that it is one of the few fish species to be part of a space mission to assess the effects of microgravity on their development.

Against this background, and notwithstanding the under-development research techniques still to be explored, the purpose of the present book is to pay homage to the zebrafish as such an exquisite alternative experimental model, celebrating all the significant achievements it has provided to the scientific community and what is yet to come.

2. From South Asia to the world and beyond

The zebrafish is a small freshwater fish native to South Asia, where it is naturally found in India, Bangladesh, Pakistan, and Nepal. The reason it is an extensively studied vertebrate model organism is due to the fact it can be bred rapidly in large numbers, fertilized eggs are transparent, and the embryo develops rapidly outside of the uterus, with precursors to all major organs taking shape within 36 hours of fertilization, making it attractive to study vertebrate development, physiology, and diseases.

Besides, over the last two decades, the zebrafish has joined the outstanding list of model organisms for biomedical research since it is amenable to genetics with a full suite of tools and genomic resources [1]. Just recently, the tenth anniversary of the publication of the complete zebrafish genome was celebrated. The zebrafish genome project kicked off at the Wellcome Trust Sanger Institute in 2001 and was completed in 2013 [2]. The sequencing provided evidence of more than 26,000 protein-coding genes, the most extensive set of any vertebrate sequenced so far. Additionally, the project demonstrated the high homology between zebrafish and humans, which share 70% genetic homology; perhaps more importantly, regarding genes that cause human diseases, around 84% of the zebrafish genes have a human counterpart.

The deep knowledge of the zebrafish genome has made it a powerful and versatile model organism, boosting its use in various fields of research, and contributing significantly to our understanding of fundamental biological processes and human health. Such advancements allowed thousands of mutants, transgenic lines, and a wealth of know-how techniques for embryological manipulation, drug discovery, among others. Genome sequencing, for example, is crucial for designing and implementing genetic manipulations, such as gene knock-in and knockout through CRISPR/Cas9 technology [3]. Understanding the genomic context is essential for precision targeting and accurately interpreting the outcomes of these manipulations. Moreover, it contributes to comparative genomics, biotechnological applications, and drug discovery. Zebrafish’s genome sequencing bridges the gap between basic research and clinical applications, facilitating translational research. It provides insights into the genetic basis of diseases, enabling the development of novel diagnostics, therapies, and interventions, helping identify potential drug targets, and understanding the genetic factors influencing drug response and toxicity.

The zebrafish research advancements and information have been shared worldwide through several platforms such as the Zebrafish Information Network (ZFIN). ZFIN serves as a comprehensive and centralized resource for the zebrafish research community by providing essential information and tools for researchers studying Danio rerio. Also, it offers a user-friendly database encompassing curated data on zebrafish genes, mutants, transgenic lines, antibodies, and other molecular and phenotypic information. Moreover, it is well-known that using zebrafish as a model organism has substantially increased scientific publications over the years. Its popularity across disciplines has contributed to a growing body of literature, which might continue to expand.

3. New insights and research prospects from the zebrafish

Taken as a successful ever-expanding experimental model, zebrafish has already been instrumental in numerous scientific research; current investigations have still yielded advances in many significant fields. In cancer research, zebrafish models have played a fundamental part in studying cancer biology, including tumor initiation, progression, and metastasis. Researchers can also use it in drug screening assays to identify compounds with therapeutic potential [4]. The high-throughput nature of these screens allows for the rapid evaluation of a large number of potential drug candidates, including screening for potential anti-cancer drugs. Other areas benefiting from the gathered knowledge are neurological disorders, but not exclusively, where zebrafish are employed to study various aspects of neurobiology, including neural development, in addition to cardiovascular research and regeneration.

Notably, zebrafish’s regenerative abilities in the heart make it particularly interesting for cardiac regeneration studies, in conjunction with the fact that zebrafish can serve as a regeneration model for lateral line hair cells during early-life stages, photoreceptor cells and retinal neurons, and tail fins after injury. Tail fin amputations work as a protocol to analyze their regrowth to test for the local inflammatory response and mutations. It was also demonstrated that histone demethylation occurs at the amputation site, transitioning the cells to a so-called active, regenerative, stem cell-like state [5]. The screening of gene expression during regeneration additionally helped to identifying critical signaling pathways which take part in the process, such as Wnt signaling and fibroblast growth factor [6].

Looking ahead, considerable advancements in zebrafish research are driven by the substantial demand for alternative models in animal experimentation. Zebrafish emerges as a pivotal link between in vitro and in vivo models, maintaining the complex features of a complete vertebrate organism. Zebrafish contribution continues to expand, underscoring its significance in experimental biology and advancing our understanding of fundamental biological processes and human health, fostering a promising trajectory for future scientific endeavors.