Telophase correction refines division orientation in stratified epithelia
- University of North Carolina at Chapel Hill, United States
- University of California, San Francisco, United States
Abstract
During organogenesis, precise control of spindle orientation balances proliferation and differentiation. In the developing murine epidermis, planar and perpendicular divisions yield symmetric and asymmetric fate outcomes, respectively. Classically, division axis specification involves centrosome migration and spindle rotation, events occurring early in mitosis. Here, we identify a novel orientation mechanism which corrects erroneous anaphase orientations during telophase. The directionality of reorientation correlates with the maintenance or loss of basal contact by the apical daughter. While the scaffolding protein LGN is known to determine initial spindle positioning, we show that LGN also functions during telophase to reorient oblique divisions toward perpendicular. The fidelity of telophase correction also relies on the tension-sensitive adherens junction proteins vinculin, α-E-catenin, and afadin. Failure of this corrective mechanism impacts tissue architecture, as persistent oblique divisions induce precocious, sustained differentiation. The division orientation plasticity provided by telophase correction may enable progenitors to adapt to local tissue needs.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for all Figures.
Article and author information
Author details
Carlos P Descovich
Danielle C Spitzer
Funding
National Institute of Dental and Craniofacial Research (Predoctoral Fellowship F31 DE026956)
- Kendall J Lough
National Institute of Dental and Craniofacial Research (Career Development Award K08 DE026537)
- Kevin M Byrd
Sidney Kimmel Foundation for Cancer Research (Scholar Award SKF-15-165)
- Scott E Williams
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Valerie Horsley, Yale University, United States
Ethics
Animal experimentation: Mice were housed in an AAALAC-accredited (#329; June 2017), USDA registered (55-R-0004), NIH welfare-assured (D16-00256 (A3410-01)) animal facility. All procedures were performed under IACUC-approved animal protocols (19-155).
Version history
- Received: June 11, 2019
- Accepted: December 12, 2019
- Accepted Manuscript published: December 13, 2019 (version 1)
- Version of Record published: January 14, 2020 (version 2)
Copyright
© 2019, Lough 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.
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Telophase correction refines division orientation in stratified epithelia
eLife 8:e49249.
https://doi.org/10.7554/eLife.49249
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