ZFIN ID: ZDB-PUB-170519-15
Development of a Whole Organism Platform for Phenotype-Based Analysis of IGF1R-PI3K-Akt-Tor Action
Liu, C., Dai, W., Bai, Y., Chi, C., Xin, Y., He, G., Mai, K., Duan, C.
Date: 2017
Source: Scientific Reports   7: 1994 (Journal)
Registered Authors: Duan, Cunming
Keywords: Cell proliferation, Insulin signalling
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Biomarkers
  • Calcium/metabolism
  • Cell Proliferation
  • Gene Expression
  • Genes, Reporter
  • Phosphatidylinositol 3-Kinases/metabolism*
  • Proto-Oncogene Proteins c-akt/metabolism*
  • Receptor, IGF Type 1/metabolism*
  • Signal Transduction*
  • Stress, Physiological
  • Zebrafish
PubMed: 28515443 Full text @ Sci. Rep.
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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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