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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wang, G; Rajpurohit, SK; Delaspre, F; Walker, SL; White, DT; Ceasrine, A; Kuruvilla, R; Li, R-J; Shim, JS; Liu, JO; Parsons, MJ; Mumm, JS

Published Date

  • July 28, 2015

Published In

Volume / Issue

  • 4 /

PubMed ID

  • 26218223

Pubmed Central ID

  • 26218223

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

International Standard Serial Number (ISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.08261

Language

  • eng