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

Scientific Reports
Chengdong LiuCunming Duan

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.

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Citations

Mar 21, 2020·Frontiers in Endocrinology·Cumming Duan, John B Allard
May 28, 2019·The Journal of Clinical Endocrinology and Metabolism·Berta Mas-ParésJudit Bassols
Apr 27, 2021·Frontiers in Cell and Developmental Biology·Shuang LiCunming Duan
Sep 22, 2021·Journal of Cell Science·Yi XinCunming Duan

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Datasets Mentioned

BETA
BX321894.8

Methods Mentioned

BETA
transgenic
FACS
PCR
Fluorescence-activated cell sorting
Flow Cytometry

Software Mentioned

Leica LAS AF
GraphPad Prism

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