Yukinobu Arata

Extracellular control of PAR protein localization during asymmetric cell division in the C. elegans embryo

The axis of asymmetric cell division is controlled to determine the future position of differentiated cells during animal development. The asymmetric localization of PAR proteins in the Drosophila neuroblast and C. elegans embryo are aligned with the axes of the embryo. However, whether extracellular or intracellular signals determine the orientation of the localization of PAR proteins remains controversial. In C. elegans, the P0 zygote and germline cells (P1, P2, and P3) undergo a series of asymmetric cell divisions. Interestingly, the axis of the P0 and P1 divisions is opposite to that of the P2 and P3 divisions. PAR-2, a ring-finger protein, and PAR-1, a kinase, relocalize to the anterior side of the P2 and P3 germline precursors at the site of contact with endodermal precursors. Using an in vitro method, we have found that the PAR-2 protein is distributed asymmetrically in the absence of extracellular signals, but the orientation of the protein localization in the P2 and P3 cells is determined by contact with endodermal precursor cells. Our mutant analyses suggest that mes-1 and src-1, which respectively encode a transmembrane protein and a tyrosine kinase, were not required to establish the asymmetric distribution of PAR-2, but were required to determine its orientation at the site of contact with the endodermal precursors. The PAR-2 localization during the asymmetric P2 and P3 divisions is controlled by extracellular signals via MES-1/SRC-1 signaling. Our findings suggest that Src functions as an evolutionarily conserved molecular link that coordinates extrinsic cues with PAR protein localization.

Power law relationship between cell cycle duration and cell volume in the early embryonic development of Caenorhabditis elegans.

Cell size is a critical factor for cell cycle regulation. In Xenopus embryos after midblastula transition (MBT), the cell cycle duration elongates in a power law relationship with the cell radius squared. This correlation has been explained by the model that cell surface area is a candidate to determine cell cycle duration. However, it remains unknown whether this second power law is conserved in other animal embryos. Here, we found that the relationship between cell cycle duration and cell size in Caenorhabditis elegans embryos exhibited a power law distribution. Interestingly, the powers of the time-size relationship could be grouped into at least three classes: highly size-correlated, moderately size-correlated, and potentially a size-non-correlated class according to C. elegans founder cell lineages (1.2, 0.81, and <0.39 in radius, respectively). Thus, the power law relationship is conserved in Xenopus and C. elegans, while the absolute powers in C. elegans were different from that in Xenopus. Furthermore, we found that the volume ratio between the nucleus and cell exhibited a power law relationship in the size-correlated classes. The power of the volume relationship was closest to that of the time-size relationship in the highly size-correlated class. This correlation raised the possibility that the time-size relationship, at least in the highly size-correlated class, is explained by the volume ratio of nuclear size and cell size. Thus, our quantitative measurements shed a light on the possibility that early embryonic C. elegans cell cycle duration is coordinated with cell size as a result of geometric constraints between intracellular structures.

Cortical Polarity of the RING Protein PAR-2 Is Maintained by Exchange Rate Kinetics at the Cortical-Cytoplasmic Boundary

Cell polarity arises through the spatial segregation of polarity regulators. PAR proteins are polarity regulators that localize asymmetrically to two opposing cortical domains. However, it is unclear how the spatially segregated PAR proteins interact to maintain their mutually exclusive partitioning. Here, single-molecule detection analysis in Caenorhabditis elegans embryos reveals that cortical PAR-2 diffuses only short distances, and, as a result, most PAR-2 molecules associate and dissociate from the cortex without crossing into the opposing domain. Our results show that cortical PAR-2 asymmetry is maintained by the local exchange reactions that occur at the cortical-cytoplasmic boundary. Additionally, we demonstrate that local exchange reactions are sufficient to maintain cortical asymmetry in a parameter-free mathematical model. These findings suggest that anterior and posterior PAR proteins primarily interact through the cytoplasmic pool and not via cortical diffusion.