Insulin-Related Size Regulator Identified

Researchers working with the Drosophila fruit fly model have identified a metabolic pathway controlling the number and size of cells, thereby determining the size of the animal.

Reduced insulin signaling in developing flies produces small flies with fewer and smaller cells. To understand why this should be, investigators at the University of Zurich (Switzerland; www.unizh.ch) looked at the Forkhead transcription factor FOXO, which is known to mediate the reduction in cell number associated with reduced insulin signaling.

Using microarray analysis and subsequent genetic validation, they identified d4E-BP, which encodes a translation inhibitor, as a relevant dFOXO target gene. Through genetic engineering techniques, they showed that flies with no functional FOXO looked normal but were more sensitive to oxidative stress. The flies were not smaller because they had more cells than normal insulin signaling pathway mutants. Thus if insulin was not present, FOXO played a role in reducing the number of cells in the developing fly by inhibiting cell division.

Summing up in their August 7, 2003, Journal of Biology paper, the authors wrote, "In this study we provide genetic evidence that the Drosophila FOXO homologue, dFOXO is an important downstream effector of Drosophila insulin signaling and regulator of stress resistance.”



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