RT Journal Article
SR Electronic
T1 Tension at intercellular junctions is necessary for accurate orientation of cell division in the epithelium plane
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.30.478396
DO 10.1101/2022.01.30.478396
A1 Ana Lisica
A1 Jonathan Fouchard
A1 Manasi Kelkar
A1 Tom P. J. Wyatt
A1 Julia Duque
A1 Anne-Betty Ndiaye
A1 Alessandra Bonfanti
A1 Buzz Baum
A1 Alexandre J. Kabla
A1 Guillaume T. Charras
YR 2022
UL http://biorxiv.org/content/early/2022/01/31/2022.01.30.478396.abstract
AB 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. Division perpendicular to the plane of the substrate can promote tissue stratification during development or wound healing, but also metastasis when orientation is aberrant. Much is known about the molecular mechanisms involved in setting the spindle orientation. However, less is known about the contribution of mechanical factors, such as tissue tension, in ensuring spindle orientation in the plane of the epithelium, despite epithelia being continuously subjected to mechanical stresses. Here, we used suspended epithelial monolayers devoid of extracellular matrix and subjected to varying levels of tissue tension to study the orientation of division relative to the tissue plane. We found that decreasing tissue tension by compressing the monolayers or by inhibiting myosin contractility leads to a higher frequency of out-of-plane divisions. Reciprocally, accurate in-plane division can be restored by increasing tissue tension by increasing cell contractility or by tissue stretching. By considering the full three-dimensional geometry of the epithelium, we show that spindles are sensitive to tissue tension, independently of cell shape, through its impact on the tension at subcellular surfaces. Overall, our data suggest that accurate spindle orientation in the plane of the epithelium necessitates the presence of a sufficiently large tension at intercellular junctions.Significance statement In growing epithelia, divisions are typically oriented in the plane of the tissue to drive expansion. In some organs, divisions are then re-oriented so that they 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 organisation and, in cancer, likely contribute to metastasis. While much is known about the molecular mechanisms controlling mitotic spindle orientation, less is known about the role of mechanical factors. Here we use mechanical and chemical perturbations to 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 sufficient tension across intercellular junctions.Competing Interest StatementThe authors have declared no competing interest.