Tension at intercellular junctions is necessary for accurate orientation of cell division in the epithelium plane.
Tension at intercellular junctions is necessary for accurate orientation of cell division in the epithelium plane.
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DOI：
10.1073/pnas.2201600119
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发表时间：
2022-12-06
影响因子：
11.1
通讯作者：
Charras GT
中科院分区：
文献类型：
--
作者：
Lisica A;Fouchard J;Kelkar M;Wyatt TPJ;Duque J;Ndiaye AB;Bonfanti A;Baum B;Kabla AJ;Charras GT
In growing epithelia, divisions are typically oriented in the epithelial plane to drive tissue expansion. In some organs, divisions are then reoriented to occur perpendicular to the epithelium plane to drive tissue stratification and cell differentiation. When uncontrolled, this switch in orientation can lead to defects in tissue organization and has been suggested to contribute to cancer metastasis. While much is known about the molecular machinery guiding mitotic spindle orientation, less is known about the role of mechanical factors. Here, we show that mechanics plays a role in controlling the plane of division. Overall, our data suggest that the orientation of spindles in the epithelium plane requires a threshold level of mechanical tension at intercellular junctions. The direction in which a cell divides is set by the orientation of its mitotic spindle and is important for determining cell fate, controlling tissue shape, and maintaining tissue architecture. Divisions parallel to the epithelial plane sustain tissue expansion. By contrast, divisions perpendicular to the plane promote tissue stratification and lead to the loss of epithelial cells from the tissue—an event that has been suggested to promote metastasis. Much is known about the molecular machinery involved in orienting the spindle, but less is known about the contribution of mechanical factors, such as tissue tension, in ensuring spindle orientation in the plane of the epithelium. This is important as epithelia are continuously subjected to mechanical stresses. To explore this further, we subjected suspended epithelial monolayers devoid of extracellular matrix to varying levels of tissue tension to study the orientation of cell divisions relative to the tissue plane. This analysis revealed that lowering tissue tension by compressing epithelial monolayers or by inhibiting myosin contractility increased the frequency of out-of-plane divisions. Reciprocally, increasing tissue tension by elevating cell contractility or by tissue stretching restored accurate in-plane cell divisions. Moreover, a characterization of the geometry of cells within these epithelia suggested that spindles can sense tissue tension through its impact on tension at subcellular surfaces, independently of their shape. Overall, these data suggest that accurate spindle orientation in the plane of the epithelium relies on a threshold level of tension at intercellular junctions.
