The PAR proteins are required for polarity and asymmetric localization of cell fate determinants in C. elegans embryos. In addition, several of the PAR proteins are conserved and localized asymmetrically in polarized

Asymmetric divisions generate cellular diversity during development in a wide range of organisms. During intrinsically asymmetric divisions, a polarized parent cell divides to produce daughters that are different. For such a division to occur, the division plane, which is specified by the position of the mitotic spindle, must be aligned with the axis of polarity (Bowerman and Shelton, 1999; Doe and Bowerman, 2001; Hawkins and Garriga, 1998; Jan and Jan, 2000; Rose and Kemphues, 1998). Recent work has implicated a conserved set of proteins as functioning in cellular polarity and/or asymmetric divisions in several organisms. The PAR proteins were originally identified in C. elegans as being essential for establishment of polarity and partitioning of cell fate determinants (Kemphues et al., 1988). PAR-3 and PAR-6, both PDZ domain proteins, and an atypical protein kinase C, PKC-3, are all localized to the anterior cortex of asymmetrically dividing cells in early embryos (Etemad-Moghadam et al., 1995; Hung and Kemphues, 1999; Tabuse et al., 1998). Homologs of these proteins localize to the animal pole of mature oocytes and embryos in Xenopus(Nakaya et al., 2000), to the tight junctions of epithelial cells in Xenopusand mammals (Izumi et al., 1998; Nakaya et al., 2000; Suzuki et al., 2001), and to the apical surface of epithelial cells and asymmetrically dividing neuroblasts in Drosophila (Kuchinke et al., 1998; Petronczki and Knoblich, 2001). Several studies have shown that PAR-3, PAR-6 and PKC-3 can bind to each other, and that they are interdependent upon each other for asymmetric localization (Hung and Kemphues, 1999; Izumi et al., 1998; Joberty et al., 2000; Lin et al., 2000; Petronczki and Knoblich, 2001; Qiu et al., 2000; Suzuki et al., 2001; Tabuse et al., 1998). Disruption of PAR-3 or PAR-6 in cultured mammalian epithelial cells results in a loss of junctional complexes and disruptions in surface polarity (Joberty et al., 2000; Suzuki et al., 2001). Similarly, loss of function of the DrosophilaPAR3 and PAR-6 homologs disrupts epithelial integrity and causes misorientation of asymmetric divisions in neuroblasts (Kuchinke et al., 1998; Petronczki and Knoblich, 2001). Finally, the PAR-6 protein was recently found to associate with CDC42 in mammalian cells; inhibition of CDC42 function disrupts polarity in mammals and in C. elegansembryos (Gotta et al., 2001; Joberty et al., 2000; Kay and Hunter, 2001; Lin et al., 2000; Qiu et al., 2000). Thus, it is clear that an asymmetric istribution of the PAR-3/PAR-6/PKC-3 complex is characteristic of many types of polarized cells, and some aspects of its function in polarity may be conserved as well. However, the precise means by which these proteins are localized to their appropriate cortical domains remains to be elucidated. C. elegans is an excellent animal in which to study the 4645 Development 128, 4645-4656 (2001) Printed in Great Britain © The Company of Biologists Limited 2001 DEV8813