Polarization of the Drosophila oocyte by active cortical exchange

Anterior-posterior polarization in the Drosophila oocyte requires posterior localization of oskar mRNA. oskar mRNA is produced in the anteriorly situated nurse cells, moved into the oocyte, and assembled into oskar-Staufen ribonucleoprotein particles (RNPs). These RNPs then move through the oocyte and interact with the cortex, where myosin-V binds them to the actin network and kinesin-1 removes them along cortically anchored microtubules. This cortical tug-of-war takes place against an anterior-to-posterior decrease in microtubule density. How the interplay between cytoplasmic transport and cortical binding and unbinding produces a stable posterior cap is unclear. Here, we combine quantitative microscopy, photoconversion experiments, experimental perturbations, and biophysical modeling to show that posterior localization emerges from position-dependent cortical exchange coupled to cytoplasmic diffusion. Our model, which accounts for the tendency of RNPs to demix, suggests that two key parameters that determine the observed localization pattern are the total amount of oskar and the ratio of cortical unbinding to binding rates (the exchange equilibrium constant). Given oskar volume fractions in wild-type, the measured exchange constant is such that oskar localizes to the posterior cortex without demixing. If the balance is broken, say by increasing unbinding rates, oskar irreversibly demixes into cytoplasmic droplets. This is consistent with observations from our experimental perturbations. Our results show how bulk diffusion and cortical exchange, in the face of oskar RNPs' self-attraction, convert a cytoskeletal asymmetry into robust developmental polarity.