Walston Timothy, Tuskey Christina, Edgar Lois, Hawkins Nancy, Ellis Gregory, Bowerman Bruce, Wood William, Hardin Jeff
Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
Dev Cell. 2004 Dec;7(6):831-41. doi: 10.1016/j.devcel.2004.10.008.
How cells integrate the input of multiple polarizing signals during division is poorly understood. We demonstrate that two distinct Caenorhabditis elegans Wnt pathways contribute to the polarization of the ABar blastomere by differentially regulating its duplicated centrosomes. Contact with the C blastomere orients the ABar spindle through a nontranscriptional Wnt spindle alignment pathway, while a Wnt/beta-catenin pathway controls the timing of ABar spindle rotation. The three C. elegans Dishevelled homologs contribute to these processes in different ways, suggesting that functional distinctions may exist among them. We also find that CKI (KIN-19) plays a role not only in the Wnt/beta-catenin pathway, but also in the Wnt spindle orientation pathway as well. Based on these findings, we establish a model for the coordination of cell-cell interactions and distinct Wnt signaling pathways that ensures the robust timing and orientation of spindle rotation during a developmentally regulated cell division event.
细胞在分裂过程中如何整合多个极化信号的输入尚不清楚。我们证明,秀丽隐杆线虫的两条不同的Wnt信号通路通过差异调节ABar卵裂球的复制中心体,对其极化起作用。与C卵裂球的接触通过非转录的Wnt纺锤体排列通路使ABar纺锤体定向,而Wnt/β-连环蛋白通路控制ABar纺锤体旋转的时间。秀丽隐杆线虫的三个Dishevelled同源物以不同方式参与这些过程,表明它们之间可能存在功能差异。我们还发现CKI(KIN-19)不仅在Wnt/β-连环蛋白通路中起作用,也在Wnt纺锤体定向通路中起作用。基于这些发现,我们建立了一个细胞间相互作用与不同Wnt信号通路协调的模型,该模型确保了在发育调控的细胞分裂事件中纺锤体旋转的稳健时间和定向。