
First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic β-cell mass
- Cited 47
- Views 5,901
- Annotations
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 β cells in the pancreas. Twenty-four 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.
Article and author information
Author details
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved animal care and use committee (ACUC) protocols of Johns Hopkins University and Georgia Regents University
Reviewing Editor
- Tanya T Whitfield, University of Sheffield, United Kingdom
Publication history
- Received: April 21, 2015
- Accepted: July 24, 2015
- Accepted Manuscript published: July 28, 2015 (version 1)
- Version of Record published: August 14, 2015 (version 2)
Copyright
© 2015, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 5,901
- Page views
-
- 1,104
- Downloads
-
- 47
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
Downloads (link to download the article as PDF)
Download citations (links to download the citations from this article in formats compatible with various reference manager tools)
Open citations (links to open the citations from this article in various online reference manager services)
Further reading
-
- Cell Biology
- Physics of Living Systems
-
- Cell Biology
- Developmental Biology