Fates-shifted, a novel F-box protein that targets Bicoid for degradation, regulates developmental fate determination in Drosophila embryos

Bicoid (Bcd) is a morphogenetic protein that instructs patterning along the anterior-posterior (A-P) axis in Drosophila embryos. Despite extensive studies, what controls the formation of a normal concentration gradient of Bcd remains an unresolved and controversial question. In this report we show that Bcd protein degradation is mediated by the ubiquitin-proteasome pathway. We identify a novel F-box protein, encoded by fates-shifted (fsd), that plays an important role in Bcd protein degradation by targeting it for ubiquitination. Embryos from females lacking fsd have an altered Bcd gradient profile, resulting in a shift of the fatemap along the A-P axis. Our study represents a first experimental demonstration that, contrary to an alternative hypothesis, Bcd protein degradation is required for normal gradient formation and developmental fate determination.