Trends in Cell Biology
Volume 23, Issue 12, December 2013, Pages 584-586
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Science & Society
Special Issue: Translational Cell Biology
Of fish and men: using zebrafish to fight human diseases

https://doi.org/10.1016/j.tcb.2013.09.009Get rights and content

Long restricted to the field of developmental biology, the use of the zebrafish (Danio rerio) has extended to the study of human pathogenesis. Fostered by the rapid adaptation of new technologies, the design and analysis of fish models of human diseases have contributed important findings that are now making their way from aquariums to clinics. Here we outline the clinical relevance of the zebrafish as a model organism.

Section snippets

Disease modeling: is the zebrafish the new mouse?

Understanding and fighting diseases require the right tools. Some aspects of disease biology and treatment, such as tissue homeostasis, interactions between cells and their microenvironment, and response to drugs, cannot be fully recapitulated in vitro. There is thus a clear need for reliable animal models. Over the past 20 years, the mouse (Mus musculus) has become the inescapable preclinical model. Despite its strengths as a mammalian system, the mouse has experimental limitations that

Insights from zebrafish models

Numerous fish models of human diseases have been generated and studied, ranging from blood disorders and muscular dystrophies to neurodegenerative syndromes and cancer [4] (Figure 1). To illustrate the use of zebrafish for disease modeling, we first focus on selected blood disorders, which constitute the first human pathologies modeled in fish, in part due to the high degree of conservation of hematopoiesis between fish and human. Because cancer modeling in zebrafish has also become a field of

From tank to bedside

The possibility of collecting thousands of synchronized zebrafish embryos as well as their easy handling make them particularly amenable to chemical treatment. Accordingly, numerous chemical screens have been successfully performed in the fish [12]. One such screen looking for chemicals that would block formation of the neural crest, from which melanocytes arise, led to the identification of leflunomide, an inhibitor of pyrimidine synthesis [13]. Leflunomide was shown to trigger a pause in the

Concluding remarks: the translational future of the zebrafish

The generation of faithful zebrafish models is fueled by our knowledge of the genetics of human diseases. The recent development of deep-sequencing strategies on large sets of human tumor samples may yield novel insights into the genetic determinants of malignant transformation. Accordingly, the number of zebrafish models of cancer will continue to rise. The range of available techniques for the manipulation of zebrafish is increasing, thus offering new options to build models. Similar to

Disclaimer statement

L.I.Z. is a founder and stockholder of Fate, Inc. and Scholar Rock and a scientific advisor for Stemgent.

Acknowledgments

The authors thank Elliott J. Hagedorn for critical reading of the manuscript. This work was supported by NIH grant 5 R01 CA103846-10. In addition, L.I.Z. is a Howard Hughes Medical Institute Investigator and J.A. received support from the Foundation Bettencourt–Schueller.

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