Open AccessDevelopment of a Whole Organism Platform for Phenotype-Based Analysis of IGF1R-PI3K-Akt-Tor Action
Author(s) -
Chengdong Liu,
Wei Dai,
Yan Bai,
Chang-Feng Chi,
Xin Yi,
Gang He,
Kangsen Mai,
Cunming Duan
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-01687-3
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , biology , microbiology and biotechnology , zebrafish , phenotype , insulin like growth factor 1 receptor , model organism , signal transduction , computational biology , cell growth , organism , genetics , growth factor , gene , receptor
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 [Ca 2+ ] 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.