1. Zebrafish development and regeneration: new tools for biomedical research.
- Author
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Brittijn SA, Duivesteijn SJ, Belmamoune M, Bertens LF, Bitter W, de Bruijn JD, Champagne DL, Cuppen E, Flik G, Vandenbroucke-Grauls CM, Janssen RA, de Jong IM, de Kloet ER, Kros A, Meijer AH, Metz JR, van der Sar AM, Schaaf MJ, Schulte-Merker S, Spaink HP, Tak PP, Verbeek FJ, Vervoordeldonk MJ, Vonk FJ, Witte F, Yuan H, and Richardson MK
- Subjects
- Amino Acid Sequence, Animals, Automation, Computational Biology, Gene Library, Humans, Immune System, Inflammation, Models, Biological, Molecular Sequence Data, Phenotype, Sequence Homology, Amino Acid, Body Patterning, Developmental Biology methods, Zebrafish embryology, Zebrafish physiology
- 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.
- Published
- 2009
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