A High-Content Screen Reveals New Small-Molecule Enhancers of Ras/Mapk Signaling as Probes for Zebrafish Heart Development.

ABSTRACT: Zebrafish is the preferred vertebrate model for high throughput chemical screens to discover modulators of complex biological pathways. We adapted a transgenic zebrafish line, Tg(dusp6:EGFP), which reports on fibroblast growth factor (Fgf)/Ras/Mapk activity, into a quantitative, high-content chemical screen to identify novel Fgf hyperactivators as chemical probes for zebrafish heart development and regeneration. We screened 10,000 compounds from the TimTec ActiProbe library, and identified several structurally distinct classes of molecules that enhanced Fgf/Ras/Mapk signaling. We chose three agents-ST020101, ST011282, and ST006994-for confirmatory and functional studies based on potency, repeatability with repurchased material, favorable whole organism toxicity, and evidence of structure⁻a

SUBMITTER: Saydmohammed M 

PROVIDER: S-EPMC6099644 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature