title: Wnt regulates spindle asymmetry to generate asymmetric nuclear β-catenin in C. elegans.
abstract: Extrinsic signals received by a cell can induce remodeling of the cytoskeleton, but the downstream effects of cytoskeletal changes on gene expression have not been well studied. Here, we show that during telophase of an asymmetric division in C. elegans, extrinsic Wnt signaling modulates spindle structures through APR-1/APC, which in turn promotes asymmetrical nuclear localization of WRM-1/β-catenin and POP-1/TCF. APR-1 that localized asymmetrically along the cortex established asymmetric distribution of astral microtubules, with more microtubules found on the anterior side. Perturbation of the Wnt signaling pathway altered this microtubule asymmetry and led to changes in nuclear WRM-1 asymmetry, gene expression, and cell-fate determination. Direct manipulation of spindle asymmetry by laser irradiation altered the asymmetric distribution of nuclear WRM-1. Moreover, laser manipulation of the spindles rescued defects in nuclear POP-1 asymmetry in wnt mutants. Our results reveal a mechanism in which the nuclear localization of proteins is regulated through the modulation of microtubules.
authors.affiliation: Laboratory for Cell Fate Decision, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugioka
authors.forename: Kota
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sawa
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D016547:Kinesins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; C120104:WRM-1 protein, C elegans; D051153:Wnt Proteins; D051176:beta Catenin; D016547:Kinesins