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Sci Rep. 2017 May 17;7(1):1994. doi: 10.1038/s41598-017-01687-3.

Development of a Whole Organism Platform for Phenotype-Based Analysis of IGF1R-PI3K-Akt-Tor Action.

Liu C1,2, Dai W2,3, Bai Y2, Chi C2,4, Xin Y2, He G1, Mai K1, Duan C5.

Author information

1
The Key Laboratory of Mariculture, Education Ministry of China and College of Fisheries, Ocean University of China, Qingdao, 266003, China.
2
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
3
Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA.
4
National Engineering Research Center for Marine Facilities Aquaculture, School of Marine Science and Technology, Zhejiang Ocean University, Zhoushan, 316022, China.
5
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA. cduan@umich.edu.

Abstract

Aberrant regulation of the insulin-like growth factor (IGF)/insulin (IIS)-PI3K-AKT-TOR signaling pathway is linked to major human diseases, and key components of this pathway are targets for therapeutic intervention. Current assays are molecular target- or cell culture-based platforms. Due to the great in vivo complexities inherited in this pathway, there is an unmet need for whole organism based assays. Here we report the development of a zebrafish transgenic line, Tg(igfbp5a:GFP), which faithfully reports the mitotic action of IGF1R-PI3K-Akt-Tor signaling in epithelial cells in real-time. This platform is well suited for high-throughput assays and real-time cell cycle analysis. Using this platform, the dynamics of epithelial cell proliferation in response to low [Ca2+] stress and the distinct roles of Torc1 and Torc2 were elucidated. The availability of Tg(igfbp5a:GFP) line provides a whole organism platform for phenotype-based discovery of novel players and inhibitors in the IIS-PI3K-Akt-Tor signaling pathway.

PMID:
28515443
PMCID:
PMC5435685
DOI:
10.1038/s41598-017-01687-3
[Indexed for MEDLINE]
Free PMC Article

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