Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
Centro de Biología Molecular Severo Ochoa, 28049 Madrid, Spain.
Dev Cell. 2015 May 4;33(3):299-313. doi: 10.1016/j.devcel.2015.02.001. Epub 2015 Apr 16.
Morphogenesis, homeostasis, and regeneration of epithelial tissues rely on the accurate orientation of cell divisions, which is specified by the mitotic spindle axis. To remain in the epithelial plane, symmetrically dividing epithelial cells align their mitotic spindle axis with the plane. Here, we show that this alignment depends on epithelial cell-cell communication via semaphorin-plexin signaling. During kidney morphogenesis and repair, renal tubular epithelial cells lacking the transmembrane receptor Plexin-B2 or its semaphorin ligands fail to correctly orient the mitotic spindle, leading to severe defects in epithelial architecture and function. Analyses of a series of transgenic and knockout mice indicate that Plexin-B2 controls the cell division axis by signaling through its GTPase-activating protein (GAP) domain and Cdc42. Our data uncover semaphorin-plexin signaling as a central regulatory mechanism of mitotic spindle orientation necessary for the alignment of epithelial cell divisions with the epithelial plane.
上皮组织的形态发生、稳态和再生依赖于细胞分裂的精确定向，这由有丝分裂纺锤体轴决定。为了保持在上皮平面内，对称分裂的上皮细胞将其有丝分裂纺锤体轴与平面对齐。在这里，我们表明这种对齐取决于通过 semaphorin-plexin 信号的上皮细胞-细胞通讯。在肾脏形态发生和修复过程中，缺乏跨膜受体 Plexin-B2 或其 semaphorin 配体的肾小管上皮细胞无法正确定向有丝分裂纺锤体，导致上皮结构和功能严重缺陷。对一系列转基因和敲除小鼠的分析表明，Plexin-B2 通过其 GTPase 激活蛋白 (GAP) 结构域和 Cdc42 信号传导来控制细胞分裂轴。我们的数据揭示了 semaphorin-plexin 信号作为有丝分裂纺锤体定向的中央调节机制，对于上皮细胞分裂与上皮平面的对齐是必需的。
