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.
All data generated or analysed during this study are included in the manuscript and supporting files. Due to their large size (100s of GBs), the source movies are available upon request.
- Kara L McKinley
- Nico Stuurman
- Ronald D Vale
- Kara L McKinley
- David Castillo-Azofeifa
- Ophir D Klein
- Loic A Royer
- Christoph Schartner
- Markus Delling
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All experiments involving mice were approved by the Institutional Animal Care and Use Committee of the University of California, San Francisco (protocol #AN151723).
- Jody Rosenblatt, University of Utah, United States
© 2018, McKinley et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.