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ZIRC
ZFIN ID: ZDB-PUB-080415-3
Identification of a novel retinoid by small molecule screening with zebrafish embryos
Sachidanandan, C., Yeh, J.R., Peterson, Q.P., and Peterson, R.T.
Date: 2008
Source: PLoS One   3(4): e1947 (Journal)
Registered Authors: Sachidanandan, Chetana, Yeh, Jing-Ruey (Joanna)
Keywords: Embryos, Zebrafish, Small molecules, Library screening, Phenotypes, Hormone receptor signaling, In situ hybridization, Retinoic acid
MeSH Terms:
  • Aminobenzoates/pharmacology*
  • Animals
  • Body Patterning
  • Cell Line
  • Gene Expression Regulation, Developmental*
  • Humans
  • In Situ Hybridization
  • Models, Biological
  • Receptors, Retinoic Acid/metabolism
  • Retinoid X Receptors/metabolism
  • Retinoids/metabolism*
  • Signal Transduction
  • Tretinoin/metabolism
  • Triazines
  • Zebrafish
  • Zebrafish Proteins/metabolism
  • meta-Aminobenzoates
PubMed: 18398471 Full text @ PLoS One
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ABSTRACT
Small molecules have played an important role in delineating molecular pathways involved in embryonic development and disease pathology. The need for novel small molecule modulators of biological processes has driven a number of targeted screens on large diverse libraries. However, due to the specific focus of such screens, the majority of the bioactive potential of these libraries remains unharnessed. In order to identify a higher proportion of compounds with interesting biological activities, we screened a diverse synthetic library for compounds that perturb the development of any of the multiple organs in zebrafish embryos. We identified small molecules that affect the development of a variety of structures such as heart, vasculature, brain, and body-axis. We utilized the previously known role of retinoic acid in anterior-posterior (A-P) patterning to identify the target of DTAB, a compound that caused A-P axis shortening in the zebrafish embryo. We show that DTAB is a retinoid with selective activity towards retinoic acid receptors gamma and beta. Thus, conducting zebrafish developmental screens using small molecules will not only enable the identification of compounds with diverse biological activities in a large chemical library but may also facilitate the identification of the target pathways of these biologically active molecules.
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