Evolutionary Developmental Biology, also known as EvoDevo, explores how developmental processes shape evolutionary change. Zebrafish, with their unique genetic and developmental features, have become a cornerstone for EvoDevo research and a powerful tool for drug discovery and toxicity testing. This article introduces the science behind EvoDevo, the advantages of zebrafish as a model, and how automation is revolutionizing their use in biomedical research.
Introduction
- How do genetic changes alter development?
- How do these changes lead to new traits or species?
- How are developmental pathways conserved or modified across evolution?
At its core, EvoDevo is built on the idea that small changes in gene regulation or signaling during development can have profound effects on an organism’s form and function. By comparing species, researchers uncover the principles that govern how evolution repurposes with development to generate novelty.
Today, EvoDevo is gaining traction because it connects evolutionary biology, genetics, and developmental biology, offering powerful insights into how new functions arise and informing fields such as medicine, ecology, and synthetic biology.
Zebrafish as a Model in EvoDevo
The zebrafish (Danio rerio) is one of those model organisms whose value goes far beyond what meets the eye. As a member of the teleost fishes, a lineage that includes more than 30,000 species and represents about half of all living vertebrates, it offers a rich evolutionary context in which to study development (1). At the genetic level, zebrafish share more than 70% of their genes with humans, positioning them as a highly relevant system for uncovering the molecular mechanisms of vertebrate form and function (2).
What really sets zebrafish apart in developmental and evolutionary studies is their optical clarity and external development: embryos are transparent, fertilized externally, and develop rapidly, allowing researchers to observe developmental processes in real time. Their prolific reproduction and rapid generation times make them ideal for large-scale genetic, comparative and screening experiments. Learn more about these tiny superstars in our previous article.
In the field of EvoDevo, these attributes combine to make zebrafish a powerful platform for exploring how gene regulation and developmental pathways evolve, how new traits and forms emerge, and how conserved mechanisms can be repurposed across deep evolutionary time. The zebrafish thus act as a bridge between embryonic development, molecular genetics and evolutionary innovation.
Current Research
By comparing zebrafish DNA with that of other fish species, scientists have discovered that zebrafish went through a whole-genome duplication (WGD) early in their evolution. This event left them with extra copies of many genes, a kind of genetic “backup” that evolution could experiment with. Over time, some of these duplicated genes shared their original functions, while others took on entirely new or specialized roles, contributing to the incredible diversity of body forms and functions seen in fish today (3).
Researchers are now uncovering how these genes are regulated by small switches in the genome, known as regulatory elements. These elements control when and where a gene is active during development and are part of larger gene regulatory networks (GRNs), the systems that coordinate the activity of thousands of genes. Subtle changes in these regulatory regions can shift developmental timing and patterning, leading to new traits or species-specific morphologies (4). The same mechanisms help scientists understand the evolutionary roots of human disease genes, making zebrafish a powerful model for linking evolution, development, and health.
Zebrafish GRNs are central not only to development but also to regeneration. For example, recent studies showed that overlapping GRNs guide both developmental neurogenesis and injury-induced regeneration in the zebrafish retina (5). These findings illustrate how zebrafish can serve as a model to uncover conserved regulatory mechanisms that may eventually inform regenerative medicine in humans.
Applications in Drug Testing and Toxicity
The same signaling pathways that guide development and regeneration, such as Wnt, FGF, and Notch, are often targeted by drugs and environmental chemicals (6, 7). Signaling pathways are the cellular communication systems that transmit instructions from the environment or other cells to trigger specific gene expression programs. If a drug disrupts these pathways, it can alter gene activity, leading to developmental defects or disease. Zebrafish, with their well-characterized GRNs, are ideal for studying these effects in vivo. For example, Al‑Hamaly et al. (2024) showed that the drug Erlotinib inhibits the Wnt/β-catenin pathway in zebrafish embryos, demonstrating how this model can be used to screen compounds that target specific signaling pathways relevant to human health.
The Role of Automation
Handling large numbers of zebrafish embryos and collecting high-quality data for development, regeneration, and drug testing can be labor-intensive and prone to variability. Automated workflows address these challenges by making experiments faster, more reproducible, and cost-effective, while enabling the analysis of large datasets that would be difficult to manage manually. At Bionomous, our solutions streamline processes such as embryo sorting and imaging, helping researchers generate reliable, standardized data and accelerate discoveries. Learn more about our EggSorter here.
Conclusions & Outlooks
Over the years, zebrafish have proven to be an invaluable model for understanding evolution, development, and gene regulation, while also providing insights into regeneration and drug effects on signaling pathways. By combining these biological insights with automation technologies, researchers can efficiently generate large, high-quality datasets, accelerating discoveries and improving reproducibility.
Looking ahead, integrating zebrafish models with advanced computational models (8), AI-powered analysis, and automated workflows promises to further enhance our understanding of complex biological processes across different research organisms and enable more predictive, ethical, and scalable approaches in drug discovery and regenerative medicine.
References
- Cumplido, N., Allende, M.L. and Arratia, G. (2020) ‘From Devo to evo: Patterning, fusion and evolution of the zebrafish terminal vertebra’, Frontiers in Zoology, 17(1). doi:10.1186/s12983-020-00364-y.
- Howe, K., Clark, M., Torroja, C. et al.The zebrafish reference genome sequence and its relationship to the human genome. Nature 496, 498–503 (2013). https://doi.org/10.1038/nature12111
- Tasnim, M., Wahlquist, P. & Hill, J.T. Zebrafish: unraveling genetic complexity through duplicated genes. Dev Genes Evol 234, 99–116 (2024). https://doi.org/10.1007/s00427-024-00720-6
- Chan TM, Longabaugh W, Bolouri H, Chen HL, Tseng WF, Chao CH, Jang TH, Lin YI, Hung SC, Wang HD, Yuh CH. Developmental gene regulatory networks in the zebrafish embryo. Biochim Biophys Acta. 2009 Apr;1789(4):279-98. doi: 10.1016/j.bbagrm.2008.09.005. Epub 2008 Oct 8. PMID: 18992377.
- Lyu, P., Iribarne, M., Serjanov, D. et al. Common and divergent gene regulatory networks control injury-induced and developmental neurogenesis in zebrafish retina. Nat Commun 14, 8477 (2023). https://doi.org/10.1038/s41467-023-44142-w
- ten Berge D, Brugmann SA, Helms JA, Nusse R. Wnt and FGF signals interact to coordinate growth with cell fate specification during limb development. Development. 2008 Oct;135(19):3247-57. doi: 10.1242/dev.023176. PMID: 18776145; PMCID: PMC2756806.
- Collu GM, Hidalgo-Sastre A, Brennan K. Wnt-Notch signalling crosstalk in development and disease. Cell Mol Life Sci. 2014 Sep;71(18):3553-67. doi: 10.1007/s00018-014-1644-x. Epub 2014 Jun 19. PMID: 24942883; PMCID: PMC11113451.
- Yuan H, Mancuso CA, Johnson K, Braasch I, Krishnan A. Computational strategies for cross-species knowledge transfer and translational biomedicine. ArXiv [Preprint]. 2024 Aug 16:arXiv:2408.08503v1. PMID: 39184546; PMCID: PMC11343225.