title: Zebrafish development and regeneration: new tools for biomedical research.
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.
authors: Institute of Biology, Dept. Integrative Zoology, University of Leiden, The Netherlands.
authors: Sebastiaan A
authors: SA
authors: Brittijn
authors: Suzanne J
authors: SJ
authors: Duivesteijn
authors: Mounia
authors: M
authors: Belmamoune
authors: Laura F M
authors: LF
authors: Bertens
authors: Wilbert
authors: W
authors: Bitter
authors: Joost D
authors: JD
authors: de Bruijn
authors: Danielle L
authors: DL
authors: Champagne
authors: Edwin
authors: E
authors: Cuppen
authors: Gert
authors: G
authors: Flik
authors: Christina M
authors: CM
authors: Vandenbroucke-Grauls
authors: Richard A J
authors: RA
authors: Janssen
authors: Ilse M L
authors: IM
authors: de Jong
authors: Edo Ronald
authors: ER
authors: de Kloet
authors: Alexander
authors: A
authors: Kros
authors: Annemarie H
authors: AH
authors: Meijer
authors: Juriaan R
authors: JR
authors: Metz
authors: Astrid M
authors: AM
authors: van der Sar
authors: Marcel J M
authors: MJ
authors: Schaaf
authors: Stefan
authors: S
authors: Schulte-Merker
authors: Herman P
authors: HP
authors: Spaink
authors: Paul P
authors: PP
authors: Tak
authors: Fons J
authors: FJ
authors: Verbeek
authors: Margriet J
authors: MJ
authors: Vervoordeldonk
authors: Freek J
authors: FJ
authors: Vonk
authors: Frans
authors: F
authors: Witte
authors: Huipin
authors: H
authors: Yuan
authors: Michael K
authors: MK
authors: Richardson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001331:Automation; D019521:Body Patterning; D019295:Computational Biology; D015509:Developmental Biology / Q000379:methods*; D015723:Gene Library; D006801:Humans; D007107:Immune System; D007249:Inflammation; D008954:Models, Biological; D008969:Molecular Sequence Data; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish / Q000196:embryology* / Q000502:physiology*