Developmental cues control a precise programme of growth, proliferation and cell death which ensures that each organ within an animal reaches its characteristic size and shape. Understanding how cells "sense" the limits of organ size and respond accordingly by exiting the cell cycle or undergoing apoptosis has wide-ranging implications for both developmental and cancer biology.

Using genetic and biochemical approaches in the fruit fly Drosophila melanogaster, we and others have identified three genes that restrict organ size in vivo: salvador (sav), warts/LATS (wts) and hippo (hpo). The sav gene encodes a WW-domain containing scaffold proteins which interacts directly with the serine/threonine kinases Hpo and Wts. In the absence of either of these regulators, a failure of both developmental apoptosis and cell cycle exit leads to an increase in cell number and organ size. Thus, the Sav/Hpo/Wts complex promotes apoptosis and cell cycle exit in vivo.

Through a series of biochemical and genetic experiments, it has become apparent that Sav, Hpo and Wts promote cell cycle exit, at least in part, by restricting transcription of Cyclin E. Furthermore, Sav, Hpo and Wts trigger apoptosis by inactivating the anti-apoptotic protein DIAP1 (Drosophila Inhibitor of Apoptosis Protein), probably both via transcriptional control and by modulating its stability.