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First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic ?-cell mass.

ABSTRACT: Whole-organism chemical screening can circumvent bottlenecks that impede drug discovery. However, in vivo screens have not attained throughput capacities possible with in vitro assays. We therefore developed a method enabling in vivo high-throughput screening (HTS) in zebrafish, termed automated reporter quantification in vivo (ARQiv). In this study, ARQiv was combined with robotics to fully actualize whole-organism HTS (ARQiv-HTS). In a primary screen, this platform quantified cell-specific fluorescent reporters in >500,000 transgenic zebrafish larvae to identify FDA-approved (Federal Drug Administration) drugs that increased the number of insulin-producing ? cells in the pancreas. 24 drugs were confirmed as inducers of endocrine differentiation and/or stimulators of ?-cell proliferation. Further, we discovered novel roles for NF-?B signaling in regulating endocrine differentiation and for serotonergic signaling in selectively stimulating ?-cell proliferation. These studies demonstrate the power of ARQiv-HTS for drug discovery and provide unique insights into signaling pathways controlling ?-cell mass, potential therapeutic targets for treating diabetes.

SUBMITTER: Wang G

PROVIDER: S-EPMC4534842 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic β-cell mass.

Wang Guangliang G Rajpurohit Surendra K SK Delaspre Fabien F Walker Steven L SL White David T DT Ceasrine Alexis A Kuruvilla Rejji R Li Ruo-Jing RJ Shim Joong S JS Liu Jun O JO Parsons Michael J MJ Mumm Jeff S JS

eLife 20150728

Whole-organism chemical screening can circumvent bottlenecks that impede drug discovery. However, in vivo screens have not attained throughput capacities possible with in vitro assays. We therefore developed a method enabling in vivo high-throughput screening (HTS) in zebrafish, termed automated reporter quantification in vivo (ARQiv). In this study, ARQiv was combined with robotics to fully actualize whole-organism HTS (ARQiv-HTS). In a primary screen, this platform quantified cell-specific flu ...[more]

PMID: 26218223

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Dataset Information

First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic ?-cell mass.

Publications

First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic β-cell mass.

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