Autonomous Control of Cell and Organ Size by CHICO, a Drosophila Homolog of Vertebrate IRS1–4

• Published in: Cell 1999-06, Vol.97 (7), p.865-875
• Main Authors: Böhni, Ruth, Riesgo-Escovar, Juan, Oldham, Sean, Brogiolo, Walter, Stocker, Hugo, Andruss, Bernard F, Beckingham, Kathy, Hafen, Ernst
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Apoptosis; Body Constitution; Carrier Proteins; Cell Count; Cell Size; Drosophila; Drosophila - genetics; Drosophila - metabolism; Drosophila - physiology; Drosophila Proteins; Female; Insect Proteins - genetics; Insect Proteins - metabolism; Insulin Receptor Substrate Proteins; Intracellular Signaling Peptides and Proteins; Lipid Metabolism; Male; Molecular Sequence Data; Mutagenesis; Phosphatidylinositol 3-Kinases - metabolism; Phosphoproteins - genetics; Phosphoproteins - metabolism; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; Sequence Homology, Amino Acid; Vertebrates
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)80799-0

The control of growth is fundamental to the developing metazoan. Here, we show that CHICO, a Drosophila homolog of vertebrate IRS1–4, plays an essential role in the control of cell size and growth. Animals mutant for chico are less than half the size of wild-type flies, owing to fewer and smaller cells. In mosaic animals, chico homozygous cells grow slower than their heterozygous siblings, show an autonomous reduction in cell size, and form organs of reduced size. Although chico flies are smaller, they show an almost 2-fold increase in lipid levels. The similarities of the growth defects caused by mutations in chico and the insulin receptor gene in Drosophila and by perturbations of the insulin/IGF1 signaling pathway in vertebrates suggest that this pathway plays a conserved role in the regulation of overall growth by controling cell size, cell number, and metabolism.