Asymmetric cortical and nuclear localizations of WRM-1/β-catenin during asymmetric cell division in C. elegans

Abstract

␤-Catenin can promote adhesion at the cell cortex and mediate Wnt signaling in the nucleus. We show that, in Caenorhabditis elegans, both WRM-1/␤-catenin and LIT-1 kinase localize to the anterior cell cortex during asymmetric cell division but to the nucleus of the posterior daughter afterward. Both the cortical and nuclear localizations are regulated by Wnts and are apparently coupled. We also found that the daughters show different nuclear export rates for LIT-1. Our results indicate that Wnt signals release cortical WRM-1 from the posterior cortex to generate cortical asymmetry that may control WRM-1 asymmetric nuclear localization by regulating cell polarity.Supplemental material is available at htttp://www.genesdev.org. Asymmetric cell division is a fundamental mechanism for producing cellular diversity (Horvitz and Herskowitz 1992). Asymmetric division often involves the polarized localization and segregation of cell-fate determinants. In Drosophila, the Numb and Prospero proteins are cellfate determinants that are asymmetrically segregated into one of the daughter cells (ganglion mother cell [GMC]) (Betschinger and Knoblich 2004;Roegiers and Jan 2004). During neuroblast divisions, these proteins localize to the basal side of the cell cortex where they are segregated into the GMC. The asymmetric localizations of these molecules are regulated by Bazooka/Par-3, Par-6, and aPKC, which localize to the opposite side, i.e., the apical cell cortex. Similarly, in the Caenorhabditis elegans embryo at the one-cell stage, PAR-3, PAR-6, and aPKC localize to the anterior cortex (Kemphues 2000). Although the mechanisms are not clearly understood, these molecules control the localization of fate determinants (Numb and Prospero in Drosophila and P granules in C. elegans) to the opposite side of the cells through the regulation of cell polarity. Therefore, the cortical localization of polarity regulators appears to play important roles in asymmetric cell division, although this has not been clearly demonstrated.After the four-cell stage of C. elegans development, the polarity of many cells, including the EMS blastomere and the T hypodermal cell, is regulated by the Wnt signaling pathway (Thorpe et al. 2000;Korswagen 2002). Unlike the tissue-polarity Wnt pathway, which regulates cell polarity in Drosophila and mammals independent of ␤-catenin (Adler 2002), the Wnt pathway that controls the EMS polarity involves WRM-1/␤-catenin and the POP-1/TCF transcription factor and hence is related to the canonical Wnt pathway. Unlike ␤-catenin in other organisms, WRM-1 does not bind to cadherins and functions in Wnt signaling only, but not in cell adhesion (Korswagen et al. 2000). In the canonical Wnt pathway, the Wnt signal regulates the stability and nuclear localization of ␤-catenin (Logan and Nusse 2004). However, it is not known how the Wnt signal regulates WRM-1, especially because WRM-1 does not have the conserved phosphorylation sites of GSK3␤. Furthermore, the subcellular localization of WRM-1 has not been determined. Therefor...

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