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Publication

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

Authors Wang G, Rajpurohit SK, Delaspre F, Walker SL, White DT, Ceasrine A, Kuruvilla R, Li RJ, Shim JS, Liu JO, Parsons MJ, Mumm JS Submitted By Jeff Mumm on 8/4/2015 Status Published Journal eLife Year 2015 Date Published 7/28/2015 Volume : Pages 4 : Not Specified PubMed Reference 26218223 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). Here, 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 drugs that increased the number of insulin-producing ß cells in the pancreas. Twenty-four drugs were confirmed as inducers of endocrine differentiation and/or stimulators of ß-cell proliferation. Further, we discovered novel roles for NF-?B signaling in regulating endocrine differentiation and for serotonergic signaling in selectively stimulating ß-cell proliferation. These studies demonstrate the power of ARQiv-HTS for drug discovery and provide unique insights into signaling pathways controlling ß-cell mass, potential therapeutic targets for treating diabetes.

Investigators with authorship
Name Institution Jeff Mumm Augusta University

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