A systems-level interrogation identifies regulators of Drosophila blood cell number and survival

PLoS Genetics
Richelle SopkoKatja Brückner

Abstract

In multicellular organisms, cell number is typically determined by a balance of intracellular signals that positively and negatively regulate cell survival and proliferation. Dissecting these signaling networks facilitates the understanding of normal development and tumorigenesis. Here, we study signaling by the Drosophila PDGF/VEGF Receptor (Pvr) in embryonic blood cells (hemocytes) and in the related cell line Kc as a model for the requirement of PDGF/VEGF receptors in vertebrate cell survival and proliferation. The system allows the investigation of downstream and parallel signaling networks, based on the ability of Pvr to activate Ras/Erk, Akt/TOR, and yet-uncharacterized signaling pathway/s, which redundantly mediate cell survival and contribute to proliferation. Using Kc cells, we performed a genome wide RNAi screen for regulators of cell number in a sensitized, Pvr deficient background. We identified the receptor tyrosine kinase (RTK) Insulin-like receptor (InR) as a major Pvr Enhancer, and the nuclear hormone receptors Ecdysone receptor (EcR) and ultraspiracle (usp), corresponding to mammalian Retinoid X Receptor (RXR), as Pvr Suppressors. In vivo analysis in the Drosophila embryo revealed a previously unrecognized role...Continue Reading

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Citations

Jul 27, 2015·Current Opinion in Cell Biology·Aparna RatheeshDaria E Siekhaus
Apr 28, 2016·Seminars in Immunology·Katrina S Gold, Katja Brückner
Nov 2, 2016·Biology Open·Yongfeng GuoLaura A Buttitta
Apr 29, 2020·G3 : Genes - Genomes - Genetics·Daniel BakopoulosTravis K Johnson
Mar 30, 2021·Frontiers in Cell and Developmental Biology·Anjeli MaseKatja Brückner

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Methods Mentioned

BETA
sumoylation
GTPase
two-hybrid
affinity purification
transgenic
Transfection
Fluorescence-activated cell sorting
PCR
RNA-Seq
gene knockdown

Software Mentioned

CFX Manager
ZDiffFinal
TreeView
modEncode
DIOPT Integrative Ortholog Prediction Tool
ProbeFinder
COMPLEAT
ImageJ

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