Lovegrove Holly E, Hulmes Georgia E, Ghadaouia Sabrina, Revell Christopher, Giralt-Pujol Marta, Alhashem Zain, Pena Andreia, Nogare Damian D, Appleton Ellen, Costa Guilherme, Mort Richard L, Ballestrem Christoph, Jones Gareth W, Manning Cerys S, Chitnis Ajay B, Franco Claudio A, Linker Claudia, Bentley Katie, Herbert Shane P
Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK.
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
Science. 2025 May;388(6746):eadu9628. doi: 10.1126/science.adu9628. Epub 2025 May 1.
During tissue formation, dynamic cell shape changes drive morphogenesis while asymmetric divisions create cellular diversity. We found that the shifts in cell morphology that shape tissues could concomitantly act as conserved instructive cues that trigger asymmetric division and direct core identity decisions underpinning tissue building. We performed single-cell morphometric analyses of endothelial and other mesenchymal-like cells. Distinct morphological changes switched cells to an "isomorphic" mode of division, which preserved pre-mitotic morphology throughout mitosis. In isomorphic divisions, interphase morphology appeared to provide a geometric code defining mitotic symmetry, fate determinant partitioning, and daughter state. Rab4-positive endosomes recognized this code, allowing them to respond to pre-mitotic morphology and segregate determinants accordingly. Thus, morphogenetic shape change sculpts tissue form while also generating cellular heterogeneity, thereby driving tissue assembly.