Brittijn, S. A. and Duivesteijn, S. J. and Belmamoune, M. and Bertens, L. F. and Bitter, W. and Bruijn de, J. D. and Champagne, D.L. and Cuppen, E.P.J.G. and Flik, G. and Vandenbroucke-Grauls, C. M. and Janssen, R. A. and Jong de, I. M. and Kloet de, E. R. and Kros, A. and Meijer, A.H. and Metz, J. R. and Sar van der, A. M. and Schaaf, M. J. and Schulte-Merker, S. and Spaink, H.P. and Tak, P. P. and Verbeek, F. J. and Vervoordeldonk, M. J. and Vonk, F. J. and Witte, F. and Yuan, H. and Richardson, M. K. (2009) Zebrafish development and regeneration: new tools for biomedical research. The International journal of developmental biology, 53, 835-50. ISSN 1696-3547.
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Official URL: http://dx.doi.org/10.1387/ijdb.082615sb
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.
|Deposited On:||25 Jan 2010|
|Last Modified:||31 Dec 2011 04:00|
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