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

Guangliang Wang, Surendra Kumar Rajpurohit, Fabien Delaspre, Steven L Walker, David T White, Alexis Ceasrine, Rejji Kuruvilla, Ruo-Jing Li, Joong S Shim, Jun O Liu, Michael J Parsons, Jeff S Mumm

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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 β cells in the pancreas. 24 drugs were confirmed as inducers of endocrine differentiation and/or stimulators of β-cell proliferation. Further, we discovered novel roles for NF-κB signaling in regulating endocrine differentiation and for serotonergic signaling in selectively stimulating β-cell proliferation. These studies demonstrate the power of ARQiv-HTS for drug discovery and provide unique insights into signaling pathways controlling β-cell mass, potential therapeutic targets for treating diabetes.

Original languageEnglish (US)
JournaleLife
Volume4
DOIs
StatePublished - 2015

Fingerprint Dive into the research topics of 'First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic β-cell mass'. Together they form a unique fingerprint.

Cite this