PUBLICATION
A Chemical Genetic Screen for Cell Cycle Inhibitors in Zebrafish Embryos
- Authors
- Murphey, R.D., Stern, H.M., Straub, C.T., and Zon, L.I.
- ID
- ZDB-PUB-061116-17
- Date
- 2006
- Source
- Chemical Biology & Drug Design 68(4): 213-219 (Journal)
- Registered Authors
- Stern, Howard, Zon, Leonard I.
- Keywords
- none
- MeSH Terms
-
- Animals
- Aphidicolin/administration & dosage
- Cell Cycle/drug effects*
- Cell Cycle/genetics
- Cell Cycle/physiology
- Cell Line
- DNA/metabolism
- Dimethyl Sulfoxide/administration & dosage
- Drug Evaluation, Preclinical/methods*
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/metabolism
- Flow Cytometry
- Histones/metabolism
- Immunohistochemistry
- Mice
- Mitosis/drug effects
- Mitosis/genetics
- Mitosis/physiology
- NIH 3T3 Cells
- Nocodazole/administration & dosage
- Pharmaceutical Preparations/administration & dosage*
- Pharmaceutical Preparations/classification
- Phenotype
- Phosphorylation/drug effects
- Tubulin/metabolism
- Zebrafish/embryology*
- Zebrafish/genetics
- PubMed
- 17105485 Full text @ Chem. Biol. Drug Des.
Citation
Murphey, R.D., Stern, H.M., Straub, C.T., and Zon, L.I. (2006) A Chemical Genetic Screen for Cell Cycle Inhibitors in Zebrafish Embryos. Chemical Biology & Drug Design. 68(4):213-219.
Abstract
Chemical genetic screening is an effective strategy to identify compounds that alter a specific biological phenotype. As a complement to cell line screens, multicellular organism screens may reveal additional compounds. The zebrafish embryo is ideal for small molecule studies because of its small size and the ease of waterborne treatment. We first examined a broad range of known cell cycle compounds in embryos using the mitotic marker phospho-histone H3. The majority of the known compounds exhibited the predicted cell cycle effect in embryos. To determine whether we could identify novel compounds, we screened a 16 320-compound library for alterations of pH3. This screen revealed 14 compounds that had not been previously identified as having cell cycle activity despite numerous mitotic screens of the same library with mammalian cell lines. With six of the novel compounds, sensitivity was greater in embryos than cell lines, but activity was still detected in cell lines at higher doses. One compound had activity in zebrafish embryos and cell lines but not in mammalian cell lines. The remaining compounds exhibited activity only in embryos. These findings demonstrate that small molecule screens in zebrafish can identify compounds with novel activity and thus may be useful tools for chemical genetics and drug discovery.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping