Tribbles coordinates mitosis and morphogenesis in Drosophila by regulatingstring/CDC25 proteolysis

Morphogenesis and cell differentiation in multicellular organisms often req uire accurate control of cell divisions. We show that a novel cell cycle re gulator, tribbles, is critical for this control during Drosophila developme nt. During oogenesis, the level of tribbles affects the number of germ cell divisions as well as oocyte determination. The mesoderm anlage enters mito sis prematurely in tribbles mutant embryos, leading to gastrulation defects . We show that Tribbles acts by specifically inducing degradation of the CD C25 mitotic activators String and Twine via the proteosome pathway. By regu lating CDC25, Tribbles serves to coordinate entry into mitosis with morphog enesis and cell fate determination.