INTRODUCTION Asymmetries established during the first cell cycle of the C. elegans embryo are necessary for proper patterning and establishment of differential cell fates in the early blastomeres

Asymmetries established during the first cell cycle of the C. elegans embryo are necessary for proper patterning and establishment of differential cell fates in the early blastomeres (see Bowerman, 1998; Rose and Kemphues, 1998 for recent reviews). The posterior pole of the zygote is determined by the position of the sperm at fertilization (Goldstein and Hird, 1996). In response to this polarity cue, a dramatic reorganization of cytoplasm occurs that correlates with the emergence of a number of visible asymmetries, including a transient accumulation of foci of filamentous actin at the anterior pole (Strome, 1986) and localization of P granules to the posterior pole (Hird et al., 1996; Strome and Wood, 1982, 1983). The first mitotic spindle forms along the anteroposterior axis and migrates to the posterior leading to asymmetric placement of the cleavage furrow. This results in production of a larger blastomere, AB, in the anterior and a smaller blastomere, P1, in the posterior. In addition to their size difference, the AB and P1 blastomeres exhibit different cell cycle rates, different spindle orientations and different cell fate potentials (Sulston et al., 1983). Differences in cell fate potentials are reflected in differences in the distribution of the known cell fate regulators SKN-1, GLP-1, MEX-3, PIE-1 and PAL-1 in AB and P1 (Bowerman et al., 1993; Draper et al., 1996; Evans et al., 1994; Hunter and Kenyon, 1996; Mello et al., 1996). Maternal effect lethal mutations in the par (partitioning defective) genes disrupt many of the asymmetries established during the first cell cycle of embryogenesis (Cheng et al., 1995; Kemphues et al., 1988; Kirby et al., 1990; Morton et al., 1992; Watts et al., 1996), including P granule distribution, cleavage spindle placement and cell cycle asynchrony. The products of several of the par genes have been identified and have been shown to be asymmetrically distributed in the 1-cell embryo. PAR-1, a putative serine-threonine kinase, and PAR-2, a protein containing a zinc-binding motif of the ring finger class, are distributed to the posterior periphery of the 1-cell embryo (Boyd et al., 1996; Guo and Kemphues, 1995). PAR-3 and PAR-6 proteins, which contain PDZ domains, are distributed at the anterior cell cortex (Etemad-Moghadam et al., 1995; Hung and Kemphues, 1999). An atypical protein kinase C, PKC-3, has recently been identified, that co-localizes with PAR-3 and PAR-6, and gives a phenotype similar to par-3 and par-6 mutants upon RNA interference (Tabuse et al., 1998). Mutations in the par-4 gene, like mutations in the other par genes, affect several aspects of polarity, but with some unique features (Morton et al., 1992). Unlike other par mutants, 1467 Development 127, 1467-1475 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV5360