000 03013 am a22003133u 4500
042 _adc
100 1 0 _aLisica, Ana
_eauthor
_92432
700 1 0 _aFouchard, Jonathan
_eauthor
_92433
700 1 0 _aKelkar, Manasi
_eauthor
_92434
700 1 0 _aWyatt, Tom P. J.
_eauthor
_92435
700 1 0 _aDuque, Julia
_eauthor
_92436
700 1 0 _aNdiaye, Anne-Betty
_eauthor
_92437
700 1 0 _aBonfanti, Alessandra
_eauthor
_92438
700 1 0 _aBaum, Buzz
_eauthor
_92439
700 1 0 _aKabla, Alexandre J.
_eauthor
_92440
700 1 0 _aCharras, Guillaume T.
_eauthor
_92441
245 0 0 _aTension at intercellular junctions is necessary for accurate orientation of cell division in the epithelium plane
260 _bNational Academy of Sciences,
_c2022-12-01.
500 _a/pmc/articles/PMC7614093/
500 _a/pubmed/36454762
520 _aThe 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.
540 _aCopyright © 2022 the Author(s). Published by PNAS.
540 _ahttps://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
546 _aen
690 _aBiological Sciences
_92442
655 7 _aText
_2local
786 0 _nProc Natl Acad Sci U S A
856 4 1 _uhttp://dx.doi.org/10.1073/pnas.2201600119
_zConnect to this object online.
999 _c425
_d425