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ASPP2/PP1 complexes maintain the integrity of pseudostratified epithelia undergoing remodelling during morphogenesis

View ORCID ProfileChristophe Royer, Elizabeth Sandham, Elizabeth Slee, Jonathan Godwin, Nisha Veits, Holly Hathrell, Felix Zhou, Karolis Leonavicius, Jemma Garratt, Tanaya Narendra, Anna Vincent, Celine Jones, Tim Child, Kevin Coward, Chris Graham, Xin Lu, View ORCID ProfileShankar Srinivas
doi: https://doi.org/10.1101/2020.11.03.366906
Christophe Royer
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom
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  • ORCID record for Christophe Royer
  • For correspondence: christophe.royer@dpag.ox.ac.uk shankar.srinivas@dpag.ox.ac.uk
Elizabeth Sandham
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom
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Elizabeth Slee
2Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom
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Jonathan Godwin
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom
3Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom
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Nisha Veits
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom
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Holly Hathrell
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom
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Felix Zhou
2Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom
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Karolis Leonavicius
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom
4Institute of Biotechnology, Vilnius University, Vilnius, Lithuania
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Jemma Garratt
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom
6Nuffield Department of Women’s and Reproductive Health, University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, United Kingdom
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Tanaya Narendra
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom
6Nuffield Department of Women’s and Reproductive Health, University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, United Kingdom
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Anna Vincent
5Oxford Fertility, Institute of Reproductive Sciences, Oxford Business Park North, Oxford, OX4 2HW, United Kingdom
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Celine Jones
6Nuffield Department of Women’s and Reproductive Health, University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, United Kingdom
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Tim Child
5Oxford Fertility, Institute of Reproductive Sciences, Oxford Business Park North, Oxford, OX4 2HW, United Kingdom
6Nuffield Department of Women’s and Reproductive Health, University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, United Kingdom
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Kevin Coward
6Nuffield Department of Women’s and Reproductive Health, University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, United Kingdom
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Chris Graham
6Nuffield Department of Women’s and Reproductive Health, University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, United Kingdom
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Xin Lu
2Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom
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Shankar Srinivas
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom
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  • ORCID record for Shankar Srinivas
  • For correspondence: christophe.royer@dpag.ox.ac.uk shankar.srinivas@dpag.ox.ac.uk
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ABSTRACT

During development, pseudostratified epithelia undergo large scale morphogenetic events associated with increased mechanical stress. The molecular mechanisms that maintain tissue integrity in this context are poorly understood. Using a variety of genetic and imaging approaches, we uncover that the ASPP2/PP1 complex ensures proper epiblast and proamniotic cavity architecture via a mechanism that specifically prevents the most apical daughter cells from delaminating apically following cell division events. The ASPP2/PP1 complex achieves this by maintaining the integrity and organisation of the F-actin cytoskeleton at the apical surface of dividing cells. ASPP2/PP1 is also essential during gastrulation in the primitive streak, in somites and in the head fold region, suggesting that this complex is required across a wide range of pseudostratified epithelia during morphogenetic events that are accompanied by intense tissue remodelling and high cell proliferation. Finally, our study also suggests that the interaction between ASPP2 and PP1 is essential to the tumour suppressor function of ASPP2 which may be particularly relevant in the context of tissues that are subject to increased mechanical stress.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 04, 2020.
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ASPP2/PP1 complexes maintain the integrity of pseudostratified epithelia undergoing remodelling during morphogenesis
Christophe Royer, Elizabeth Sandham, Elizabeth Slee, Jonathan Godwin, Nisha Veits, Holly Hathrell, Felix Zhou, Karolis Leonavicius, Jemma Garratt, Tanaya Narendra, Anna Vincent, Celine Jones, Tim Child, Kevin Coward, Chris Graham, Xin Lu, Shankar Srinivas
bioRxiv 2020.11.03.366906; doi: https://doi.org/10.1101/2020.11.03.366906
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ASPP2/PP1 complexes maintain the integrity of pseudostratified epithelia undergoing remodelling during morphogenesis
Christophe Royer, Elizabeth Sandham, Elizabeth Slee, Jonathan Godwin, Nisha Veits, Holly Hathrell, Felix Zhou, Karolis Leonavicius, Jemma Garratt, Tanaya Narendra, Anna Vincent, Celine Jones, Tim Child, Kevin Coward, Chris Graham, Xin Lu, Shankar Srinivas
bioRxiv 2020.11.03.366906; doi: https://doi.org/10.1101/2020.11.03.366906

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