Fig. 4. A schematic of C. elegans embryos undergoing meiosis, axis specification and the first mitotic division in wild-type and different E3 ubiquitin ligase mutants. (A) During meiosis in wild-type embryos, cytoplasmic cell fate determinants are uniformly distributed in the cytoplasm and the PAR-3 protein (blue) occupies the entire cortex (a). After meiosis, the centrosomes that accompany the male pronucleus trigger the establishment of anteroposterior (AP) polarity: starting at the site of sperm aster-cortex contact, the posterior pole is specified and PAR-2 (red) spreads, replacing PAR-3 at the posterior cortex. (b,c) During this process, cytoplasmic cell fate determinants are also actively partitioned to the anterior (yellow; e.g. MEX-5 and MEX-6) and posterior (green; e.g. MEX-1, PIE-1, POS-1 and germline P granules) cytoplasm. (d) The first mitotic spindle aligns along the AP axis and cytokinesis cleaves the cell asymmetrically. (e) The respective cell fate determinants are confined to the anterior or posterior cell, and residual `mis-localized' determinants are degraded by the ubiquitin proteasome system late at the two-cell stage. (B) Partial loss-of-function APC/C mutants do not arrest in meiosis, but go on to divide mitotically. (a,b) In these embryos, the meiotic spindle often persists longer than in wild type, the sperm pronucleus does not properly associate with the cortex and an aberrant cortical PAR-2 crescent often forms. (c-e) Subsequently, polarity is lost and the embryo divides symmetrically. (C) (a-c) Loss of function of CUL-2 results in a delayed exit from meiosis II and aberrant establishment of the cortical PAR-2 domain. (c,d) In some embryos, this polarity reversal is corrected and the first division is executed properly. (d,e) Although cortical polarity is normal, the cytoplasm is not polarized properly, owing to impaired degradation of cell fate determinants. (D) No polarity defects are observed in embryos in which CUL-3 has been inactivated. (a,b) Rather, extensive cortical contractions are apparent during pronuclear migration, owing to ectopic activation of the acto-myosin cytoskeleton by MEL-26. (c,d) The failure to degrade MEI-1/katanin results in the severing of mitotic microtubules and spindle orientation defects. (e) During and after cytokinesis, MEL-26-dependent ectopic furrows appear again.