Actin

Cell

Microtubule

Spindle apparatus

Transcription factor

Biology

Gene

Dynein

Cell fate determination

Spindle pole body

Cell division

Mitosis

Cell biology

Morphogenesis

Genetics

Multicellular organism

Astral microtubules

Nature Reviews Molecular Cell Biology

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 Gαi–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 Gαi–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. The orientation of cell divisions regulates tissue architecture and cell fate and depends on mitotic spindle positioning, which is controlled by intracellular and extracellular cues. Building on work in invertebrate systems, recent studies addressed how these mechanisms operate in vertebrates, and provided initial insights into their roles in vertebrate tissue development and homeostasis.

Spindle positioning and its impact on vertebrate tissue architecture and cell fate