Asymmetric division ensures the diversification of cell lineages by generating progeny with two distinct fates. Cellular polarity must be established for cells to divide asymmetrically, and in most systems this relies on the subcellular localisation of the evolutionarily conserved partitioning defective (PAR) proteins. PAR proteins have been shown to interact with phospholipids in the lipid membrane, but the functional requirement for this interaction in polarity establishment is unclear. Now, Pierre Gönczy and colleagues demonstrate that the plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) is distributed in a PAR-dependent manner and is required for the establishment of cell polarity in the one-cell C. elegans zygote. Using live imaging and particle image velocimetry, the authors demonstrate an association between PIP2 and F-actin whereby PIP2 cortical structures and the F-actin cytoskeleton move in concert during the establishment of polarity. Small molecule-induced depletion of PIP2 during pseudocleavage results in changes to the embryo shape on the anterior side, altered F-actin organisation and variable spindle positioning. Conversely, increased cellular PIP2 levels results in sustained cortical flows towards the anterior side of the embryo and perturbed actin cytoskeletal organisation. Together, PIP2 and F-actin regulate the sizing of PAR cortical domains, not only during polarity establishment but also during polarity maintenance, and thus play an important role in setting up cellular polarity and subsequent asymmetric division in the C. elegans zygote.
