Program in Molecular Medicine
Medical Subject Headings
Amino Acid Sequence; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Division; Cell Polarity; Cyclin-Dependent Kinases; Cytoskeletal Proteins; Genes, Helminth; Mitotic Spindle Apparatus; Models, Biological; Molecular Sequence Data; Mutation; Prophase; Sequence Homology, Amino Acid; Signal Transduction; Wnt Proteins; Wnt Signaling Pathway; beta Catenin; src-Family Kinases
Cell and Developmental Biology | Cell Biology | Genetics | Molecular Genetics
In early Caenorhabditis elegans embryos, the Wingless/int (Wnt)- and Src-signaling pathways function in parallel to induce both the division orientation of the endomesoderm (EMS) blastomere and the endoderm fate of the posterior EMS daughter cell, called E. Here, we show that, in addition to its role in endoderm specification, the beta-catenin-related protein Worm armadillo 1 (WRM-1) also plays a role in controlling EMS division orientation. WRM-1 localizes to the cortex of cells in both embryos and larvae and is released from the cortex in a Wnt-responsive manner. We show that WRM-1 cortical release is disrupted in a hypomorphic cyclin-dependent protein kinase 1 (cdk-1) mutant and that WRM-1 lacking potential CDK-1 phosphoacceptor sites is retained at the cortex. In both cases, cortical WRM-1 interferes with EMS spindle rotation without affecting endoderm specification. Finally, we show that removal of WRM-1 from the cortex can restore WT division orientation, even when both Wnt- and Src-signaling pathways are compromised. Our findings are consistent with a model in which Wnt signaling and CDK-1 modify WRM-1 in a temporal and spatial manner to unmask an intrinsic polarity cue required for proper orientation of the EMS cell division axis.
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Citation: Soyoung Kim, Takao Ishidate, Rita Sharma, Martha C. Soto, Darryl Conte, Jr., Craig C. Mello, Masaki Shirayama. Wnt and CDK-1 regulate cortical release of WRM-1/β-catenin to control cell division orientation in early Caenorhabditis elegans embryos. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):E918-27. doi: 10.1073/pnas.1300769110. Link to article on publisher's site
cell polarity, embryogenesis, asymmetric cell division, Src signaling
Kim, Soyoung; Ishidate, Takao; Sharma, Rita; Soto, Martha C.; Conte, Darryl Jr.; Mello, Craig C.; and Shirayama, Masaki, "Wnt and CDK-1 regulate cortical release of WRM-1/beta-catenin to control cell division orientation in early Caenorhabditis elegans embryos" (2013). University of Massachusetts Medical School Faculty Publications. 147.