ASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis

Christophe Royer; Elizabeth Sandham; Elizabeth Slee; Falk Schneider; Christoffer B. Lagerholm; Jonathan Godwin; Nisha Veits; Holly Hathrell; Felix Zhou; Karolis Leonavicius; Jemma Garratt; Tanaya Narendra; Anna Vincent; Celine Jones; Tim Child; Kevin Coward; Chris Graham; Marco Fritzsche; Xin Lu; Shankar Srinivas

doi:10.1038/s41467-022-28590-4

ASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis

Christophe Royer, Elizabeth Sandham, Elizabeth Slee, Falk Schneider, Christoffer B. Lagerholm, Jonathan Godwin, Nisha Veits, Holly Hathrell, Felix Zhou, Karolis Leonavicius, Jemma Garratt, Tanaya Narendra, Anna Vincent, Celine Jones, Tim Child, Kevin Coward, Chris Graham, Marco Fritzsche, Xin Lu, Shankar Srinivas

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

During development, pseudostratified epithelia undergo large scale morphogenetic events associated with increased mechanical stress. Using a variety of genetic and imaging approaches, we uncover that in the mouse E6.5 epiblast, where apical tension is highest, ASPP2 safeguards tissue integrity. It achieves this by preventing the most apical daughter cells from delaminating apically following division events. In this context, ASPP2 maintains the integrity and organisation of the filamentous actin cytoskeleton at apical junctions. ASPP2 is also essential during gastrulation in the primitive streak, in somites and in the head fold region, suggesting that it is required across a wide range of pseudostratified epithelia during morphogenetic events that are accompanied by intense tissue remodelling. 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.

Original language	English (US)
Article number	941
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-28590-4
State	Published - Dec 2022
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Royer, C., Sandham, E., Slee, E., Schneider, F., Lagerholm, C. B., Godwin, J., Veits, N., Hathrell, H., Zhou, F., Leonavicius, K., Garratt, J., Narendra, T., Vincent, A., Jones, C., Child, T., Coward, K., Graham, C., Fritzsche, M., Lu, X., & Srinivas, S. (2022). ASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis. Nature communications, 13(1), Article 941. https://doi.org/10.1038/s41467-022-28590-4

Royer, C, Sandham, E, Slee, E, Schneider, F, Lagerholm, CB, Godwin, J, Veits, N, Hathrell, H, Zhou, F, Leonavicius, K, Garratt, J, Narendra, T, Vincent, A, Jones, C, Child, T, Coward, K, Graham, C, Fritzsche, M, Lu, X & Srinivas, S 2022, 'ASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis', Nature communications, vol. 13, no. 1, 941. https://doi.org/10.1038/s41467-022-28590-4

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abstract = "During development, pseudostratified epithelia undergo large scale morphogenetic events associated with increased mechanical stress. Using a variety of genetic and imaging approaches, we uncover that in the mouse E6.5 epiblast, where apical tension is highest, ASPP2 safeguards tissue integrity. It achieves this by preventing the most apical daughter cells from delaminating apically following division events. In this context, ASPP2 maintains the integrity and organisation of the filamentous actin cytoskeleton at apical junctions. ASPP2 is also essential during gastrulation in the primitive streak, in somites and in the head fold region, suggesting that it is required across a wide range of pseudostratified epithelia during morphogenetic events that are accompanied by intense tissue remodelling. 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.",

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AU - Godwin, Jonathan

AU - Veits, Nisha

AU - Hathrell, Holly

AU - Zhou, Felix

AU - Leonavicius, Karolis

AU - Garratt, Jemma

AU - Narendra, Tanaya

AU - Vincent, Anna

AU - Jones, Celine

AU - Child, Tim

AU - Coward, Kevin

AU - Graham, Chris

AU - Fritzsche, Marco

AU - Lu, Xin

AU - Srinivas, Shankar

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ASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis

Abstract

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