Zebrafish development and regeneration: new tools for biomedical research.
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.
Brittijn
Sebastiaan A
SA
Institute of Biology, Dept. Integrative Zoology, University of Leiden, The Netherlands.
Duivesteijn
Suzanne J
SJ
Belmamoune
Mounia
M
Bertens
Laura F M
LF
Bitter
Wilbert
W
de Bruijn
Joost D
JD
Champagne
Danielle L
DL
Cuppen
Edwin
E
Flik
Gert
G
Vandenbroucke-Grauls
Christina M
CM
Janssen
Richard A J
RA
de Jong
Ilse M L
IM
de Kloet
Edo Ronald
ER
Kros
Alexander
A
Meijer
Annemarie H
AH
Metz
Juriaan R
JR
van der Sar
Astrid M
AM
Schaaf
Marcel J M
MJ
Schulte-Merker
Stefan
S
Spaink
Herman P
HP
Tak
Paul P
PP
Verbeek
Fons J
FJ
Vervoordeldonk
Margriet J
MJ
Vonk
Freek J
FJ
Witte
Frans
F
Yuan
Huipin
H
Richardson
Michael K
MK
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*