Research

PDGF/VEGF signaling controls cell size in Drosophila

David Sims^1,2 , Peter Duchek^1,3 and Buzz Baum^1,4

¹  Morphogenesis Group, Ludwig Institute for Cancer Research (UCL Branch), Riding House Street, London, W1W 7BS, UK

²  Current address: The Breakthrough Toby Robins Breast Cancer Research Centre at the Institute of Cancer Research, Chester Beatty Laboratories, Fulham Road, London, SW3 6JB, UK

³  Current address: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr Bohrgasse, 1030 Vienna, Austria

⁴  Current address: MRC Laboratory for Molecular and Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK

author email corresponding author email

Genome Biology 2009, 10:R20doi:10.1186/gb-2009-10-2-r20

Published:	12 February 2009

Subject areas: Cell biology, Development, Genetics

Abstract

Background

In multicellular animals, cell size is controlled by a limited set of conserved intracellular signaling pathways, which when deregulated contribute to tumorigenesis by enabling cells to grow outside their usual niche. To delineate the pathways controlling this process, we screened a genome-scale, image-based Drosophila RNA interference dataset for double-stranded RNAs that reduce the average size of adherent S2R+ cells.

Results

Automated analysis of images from this RNA interference screen identified the receptor tyrosine kinase Pvr, Ras pathway components and several novel genes as regulators of cell size. Significantly, Pvr/Ras signaling also affected the size of other Drosophila cell lines and of larval hemocytes. A detailed genetic analysis of this growth signaling pathway revealed a role for redundant secreted ligands, Pvf2 and Pvf3, in the establishment of an autocrine growth signaling loop. Downstream of Ras1, growth signaling was found to depend on parallel mitogen-activated protein kinase (MAPK) and phospho-inositide-3-kinase (PI3K) signaling modules, as well as the Tor pathway.

Conclusions

This automated genome-wide screen identifies autocrine Pvf/Pvr signaling, upstream of Ras, MAPK and PI3K, as rate-limiting for the growth of immortalized fly cells in culture. Since, Pvf2/3 and Pvr show mutually exclusive in vivo patterns of gene expression, these data suggest that co-expression of this receptor-ligand pair plays a key role in driving cell autonomous growth during the establishment of Drosophila cell lines, as has been suggested to occur during tumor development.