Dissecting the mechanism of asymmetric cell division
Throughout biology, the ability of a cell to generate two different cell types requires the process of asymmetric division. This intrinsic asymmetry plays a crucial role in development, stem-cell like divisions and the formation of differentiated epithelial or neuronal cells. Defects in cell polarity have even been associated with metastatic spread of epithelial cancer cells. In higher eukaryotes, this ability to polarize requires the establishment of domains within the cell, which acquire distinct molecular and functional identities. The C.elegans worm model has been instrumental in studying cortical polarity. Prior to germ cell line division, a complex of conserved polarity proteins (PARs) is segregated to the anterior half of the embryo, while at the same time, a posterior domain forms in the complementary posterior region. While it is believed that these anterior and posterior polarity complexes act antagonistically, the precise mechanisms underlying this process are poorly understood and no coherent model has been achieved. Seeking to address this issue, the EU-funded ‘Establishment of cortical polarity in the one-cell C. elegans embryo’ (Goehring-Polarity) proposal aimed to explore how specific kinetic properties of PAR proteins give rise to discrete and robust cortical domains. Scientists developed several novel fluorescence microscopy techniques to address the mobility of the PARs within embryos. They discovered that PARs diffused freely, indicating that no transport process was responsible for maintaining them within the correct halves of the cell. Rather, it was suggested that the interaction of PARs with the cell membrane resulted in spatial asymmetry in membrane association and dissociation, giving rise to cell polarity. Furthermore, a physical model for cell polarity was developed where PARs were diffused within the cell to displace one another from the membrane. This proved an invaluable tool in evaluating the role of individual PARs and their role in stable pattern formation. The Goehring-Polarity work provided new insight into PARs, and their role in asymmetric cell division. These data have potential stem cell implications, possibly extending to therapeutic applications. The developed tools will also be useful to the entire scientific community for examining the kinetics of membrane-associated proteins.
