In multicellular systems, oriented cell divisions are essential for morphogenesis and homeostasis as they determine the position of daughter cells within the tissue and also, in many cases, their fate. Early studies in invertebrates led to the identification of conserved core mechanisms of mitotic spindle positioning centred on the Gα_i–LGN–NuMA–dynein complex. In recent years, much has been learnt about the way this complex functions in vertebrate cells. In particular, studies addressed how the Gα_i–LGN–NuMA–dynein complex dynamically crosstalks with astral microtubules and the actin cytoskeleton, and how it is regulated to orient the spindle according to cellular and tissue-wide cues. We have also begun to understand how dynein motors and actin regulators interact with mechanosensitive adhesion molecules sensing extracellular mechanical stimuli, such as cadherins and integrins, and with signalling pathways so as to respond to extracellular cues instructing the orientation of the division axis in vivo. In this Review, with the focus on epithelial tissues, we discuss the molecular mechanisms of mitotic spindle orientation in vertebrate cells, and how this machinery is regulated by epithelial cues and extracellular signals to maintain tissue cohesiveness during mitosis. We also outline recent knowledge of how spindle orientation impacts tissue architecture in epithelia and its emerging links to the regulation of cell fate decisions. Finally, we describe how defective spindle orientation can be corrected or its effects eliminated in tissues under physiological conditions, and the pathological implications associated with spindle misorientation.

在多细胞系统中，定向细胞分裂对于形态发生和稳态至关重要，因为它们决定子细胞在组织内的位置，在许多情况下还决定子细胞的命运。对无脊椎动物的早期研究导致了以 Gα _i –LGN-NuMA-dynein 复合物为中心的有丝分裂纺锤体定位的保守核心机制的识别。近年来，人们对这种复合物在脊椎动物细胞中的功能方式有了很多了解。特别是，研究探讨了 Gα _i –LGN-NuMA-dynein 复合物如何与星体微管和肌动蛋白细胞骨架动态串扰，以及如何根据细胞和组织范围的线索调节纺锤体的方向。我们还开始了解动力蛋白马达和肌动蛋白调节剂如何与感知细胞外机械刺激的机械敏感粘附分子（例如钙粘蛋白和整合素）以及信号通路相互作用，以便对指导体内分裂轴方向的细胞外信号做出反应。在这篇综述中，我们重点关注上皮组织，讨论了脊椎动物细胞有丝分裂纺锤体定向的分子机制，以及这种机制如何受到上皮信号和细胞外信号的调节，以在有丝分裂过程中维持组织的凝聚力。我们还概述了关于纺锤体方向如何影响上皮组织结构及其与细胞命运决定调节的新兴联系的最新知识。最后，我们描述了在生理条件下如何纠正有缺陷的纺锤体定向或消除其在组织中的影响，以及与纺锤体定向错误相关的病理学意义。