Cell polarity needs to be oriented in many developmental processes; cell migration, axonal projection, and asymmetric cell division. At the 16-cell stage in the C. elegans embryo, the P3 cell divides asymmetrically to produce the large C cell and the small P4 cell, which is a primordial germ cell. This division is oriented toward the endodermal precursor (E) such that the P4 cell forms proximal to the E cell. To study mechanisms of the asymmetric division of the P3 cell, we used an in vitro cell-isolation system. When the P3 cell was isolated and cultured alone, the P3 cell divided asymmetrically. Notably, when the isolated P3 cell was re-attached to the E cell, the P3 division was oriented toward the E cell. To identify the extracellular signals that orient the P3 division, we attached the wild-type P3 cell with the E cell of
mes-1mutants.
mes-1 encodes a transmembrane protein, which is localized at the boundary between the P3 cell and the E cell. In the recombined embryos, the P3 division failed to be directed. These results indicate that the asymmetric division of the P3 cell is polarized spontaneously, but nevertheless is directed by the extracellular signal, MES-1 from the E cell. We further demonstrated that MES-1 and SRC-1 tyrosine kinase regulate the localization of PAR-2, the polarity regulator of zygote (P0), to the boundary between the P3 cell and the E cell. Moreover, we found that
par-2 is required for asymmetric division of the P3 cell. Therefore, we conclude that MES-1/SRC-1 signaling provides a positional cue to direct the PAR-dependent cell polarization in the P3 division. We also introduce a novel approach using a program for quantitative data acquisition and mathematical modeling to understand the process of orienting cell polarity as a dynamical system.