Int. J. Dev. Biol. 53: 835 - 850 (2009)
doi: 10.1387/ijdb.082615sb
© UBC Press

Zebrafish development and regeneration: new tools for biomedical research

Sebastiaan A. Brittijn1, Suzanne J. Duivesteijn1, Mounia Belmamoune2, Laura F.M.Bertens2, Wilbert Bitter3, Joost D. de Bruijn4,5, Danielle L. Champagne6, Edwin Cuppen7, Gert Flik8, Christina M. Vandenbroucke-Grauls3, Richard A.J. Janssen9, Ilse M.L. de Jong1, Edo Ronald de Kloet6, Alexander Kros10, Annemarie H. Meijer11, Juriaan R. Metz8, Astrid M. van der Sar3, Marcel J.M. Schaaf1,11, Stefan Schulte-Merker7, Herman P. Spaink11,12, Paul P. Tak13, Fons J. Verbeek2, Margriet J. Vervoordeldonk14, Freek J. Vonk1, Frans Witte1, Huipin Yuan4 and Michael K. Richardson*,1

1Institute of Biology, Dept. Integrative Zoology, University of Leiden, The Netherlands, 2Leiden Institute for Advanced Computer Science, Leiden University, The Netherlands, 3Dept. Medical Microbiology and Infection Control, Vrije Universiteit Medisch Centrum (VUmc), Amsterdam, The Netherlands, 4Progentix BV, MB Bilthoven, The Netherlands, 5School of Engineering and Materials Science, Queen Mary University of London, U.K., 6Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research (LACDR) and Leiden University Medical Center (LUMC), The Netherlands, 7Hubrecht Institute, Utrecht, The Netherlands, 8Department of Organismal Animal Physiology, Institute for Water and Wetland Research, Radboud University Nijmegen, The Netherlands, 9BioFocusDPI, Leiden, The Netherlands, 10Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, The Netherlands, 11Institute of Biology, Dept. Molecular Cell Biology, University of Leiden, The Netherlands, 12ZFscreens, Leiden, The Netherlands, 13Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, The Netherlands and 14Arthrogen BV, Amsterdam, The Netherlands

ABSTRACT Basic research in pattern formation is concerned with the generation of phenotypes and tissues. It can therefore lead to new tools for medical research. These include phenotypic screening assays, applications in tissue engineering, as well as general advances in biomedical knowledge. Our aim here is to discuss this emerging field with special reference to tools based on zebrafish developmental biology. We describe phenotypic screening assays being developed in our own and other labs. Our assays involve: (i) systemic or local administration of a test compound or drug to zebrafish in vivo; (ii) the subsequent detection or "readout" of a defined phenotypic change. A positive readout may result from binding of the test compound to a molecular target involved in a developmental pathway. We present preliminary data on assays for compounds that modulate skeletal patterning, bone turnover, immune responses, inflammation and early-life stress. The assays use live zebrafish embryos and larvae as well as adult fish undergoing caudal fin regeneration. We describe proof-of-concept studies on the localised targeting of compounds into regeneration blastemas using microcarriers. Zebrafish are cheaper to maintain than rodents, produce large numbers of transparent eggs, and some zebrafish assays could be scaled-up into medium and high throughput screens. However, advances in automation and imaging are required. Zebrafish cannot replace mammalian models in the drug development pipeline. Nevertheless, they can provide a cost-effective bridge between cell-based assays and mammalian whole-organism models.

Keywords:

Danio rerio, zebrafish, high-throughput screening, high-content screening

*Corresponding author e-mail: m.k.richardson@biology.leidenuniv.nl