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 and Shankar Srinivas ()
Additional contact information
Christophe Royer: University of Oxford
Elizabeth Sandham: University of Oxford
Elizabeth Slee: University of Oxford
Falk Schneider: University of Oxford
Christoffer B. Lagerholm: University of Oxford
Jonathan Godwin: University of Oxford
Nisha Veits: University of Oxford
Holly Hathrell: University of Oxford
Felix Zhou: University of Oxford
Karolis Leonavicius: University of Oxford
Jemma Garratt: University of Oxford
Tanaya Narendra: University of Oxford
Anna Vincent: Oxford Business Park North
Celine Jones: University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital
Tim Child: University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital
Kevin Coward: University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital
Chris Graham: University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital
Marco Fritzsche: University of Oxford
Xin Lu: University of Oxford
Shankar Srinivas: University of Oxford

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28590-4

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