Wnt Regulates Spindle Asymmetry to Generate Asymmetric Nuclear β-Catenin in C. elegans

SummaryExtrinsic 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.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (389 K)Download as PowerPoint slideHighlights► Microtubules are necessary for asymmetric β-catenin nuclear localization ► Wnt generates asymmetric numbers of astral microtubules through cortical APC ► Microtubule asymmetry correlates with asymmetric daughter cell fates ► Laser manipulation of microtubules rescues a Wnt mutant phenotype