A/P and radial polarity in the C. elegans embryo. (A) The zygote polarizes along its A/P axis, distributing PAR proteins to distinct anterior and posterior domains. PAR-3, PAR-6, and PKC-3/aPKC enrich at the anterior cortex, whereas PAR-1 and PAR-2 concentrate at the posterior cortex. (B) During the four-cell stage (an eight-cell embryo is shown), the axis of PAR protein asymmetry switches from A/P to contacted and contact free as the embryo polarizes radially. PAR-3, PAR-6, and PKC-3 are found at contact-free surfaces of cells, whereas PAR-1 and PAR-2 are found at contacted surfaces. The single germline precursor cell (asterisk) does not polarize radially and instead retains the A/P asymmetry of PAR proteins seen in the zygote. (C) Radial polarization is initiated and maintained by a contact-induced asymmetry in Rho GTPase activity. The RhoGAP PAC-1 binds to the cortex adjacent to contact sites, where it is predicted to locally inactivate CDC-42 (CDC-42–GDP). Active CDC-42 (CDC-42–GTP) is thus restricted to contact-free surfaces where it recruits PAR-3, PAR-6, and PKC-3.