Zyg-11 and cul-2 regulate progression through meiosis II and polarity establishment in C. elegans.
The mechanisms that ensure coupling between meiotic cell cycle progression and subsequent developmental events, including specification of embryonic axes, are poorly understood. Here, we establish that zyg-11 and the cullin cul-2 promote the metaphase-to-anaphase transition and M phase exit at meiosis II in Caenorhabditis elegans. Our results indicate that ZYG-11 acts with a CUL-2-based E3 ligase that is essential at meiosis II and that functions redundantly with the anaphase-promoting complex/cyclosome at meiosis I. Our data also indicate that delayed M phase exit in zyg-11(RNAi) embryos is due to accumulation of the B type cyclin CYB-3. We demonstrate that PAR proteins and P granules become polarized in an inverted manner during the meiosis II delay resulting from zyg-11 or cul-2 inactivation, and that zyg-11 and cul-2 can regulate polarity establishment independently of a role in cell cycle progression. Furthermore, we find that microtubules appear dispensable for ectopic polarity during the meiosis II delay in zyg-11(RNAi) embryos, as well as for AP polarity during the first mitotic cell cycle in wild-type embryos. Our findings suggest a model in which a CUL-2-based E3 ligase promotes cell cycle progression and prevents polarity establishment during meiosis II, and in which the centrosome acts as a cue to polarize the embryo along the AP axis after exit from the meiotic cell cycle.
Sonneville
Rémi
R
ISREC (Swiss Institute for Experimental Cancer Research Boveresses, CH-1066 Epalinges/Lausanne, Switzerland.
Gönczy
Pierre
P
D000818:Animals; D015415:Biomarkers; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D056744:Cyclin B1; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D008540:Meiosis / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism; D009024:Morphogenesis; D009687:Nuclear Proteins / Q000378:metabolism; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; C491028:CYB-3 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; D019926:Cyclin B; D056744:Cyclin B1; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C491027:cul-2 proteins, C elegans; C454942:zyg-11 protein, C elegans