Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Loic A Royer
Chan Zuckerberg Biohub, San Francisco, United States
Department of Physiology, University of California, San Francisco, San Francisco, United States
David Castillo-Azofeifa
Department of Orofacial Sciences, University of California, San Francisco, San Francisco, United States; Program in Craniofacial Biology, University of California, San Francisco, San Francisco, United States
Markus Delling
Department of Physiology, University of California, San Francisco, San Francisco, United States
Department of Orofacial Sciences, University of California, San Francisco, San Francisco, United States; Program in Craniofacial Biology, University of California, San Francisco, San Francisco, United States; Department of Pediatrics, University of California, San Francisco, San Francisco, United States; Institute for Human Genetics, University of California, San Francisco, San Francisco, United States
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Cell division is essential to expand, shape, and replenish epithelia. In the adult small intestine, cells from a common progenitor intermix with other lineages, whereas cell progeny in many other epithelia form contiguous patches. The mechanisms that generate these distinct patterns of progeny are poorly understood. Using light sheet and confocal imaging of intestinal organoids, we show that lineages intersperse during cytokinesis, when elongated interphase cells insert between apically displaced daughters. Reducing the cellular aspect ratio to minimize the height difference between interphase and mitotic cells disrupts interspersion, producing contiguous patches. Cellular aspect ratio is similarly a key parameter for division-coupled interspersion in the early mouse embryo, suggesting that this physical mechanism for patterning progeny may pertain to many mammalian epithelia. Our results reveal that the process of cytokinesis in elongated mammalian epithelia allows lineages to intermix and that cellular aspect ratio is a critical modulator of the progeny pattern.
