ASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis

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 a...

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Vydané v:	Nature communications Ročník 13; číslo 1; s. 941 - 19
Hlavní autori:	Royer, Christophe, Sandham, Elizabeth, Slee, Elizabeth, Schneider, Falk, Lagerholm, Christoffer B., Godwin, Jonathan, Veits, Nisha, Hathrell, Holly, Zhou, Felix, Leonavicius, Karolis, Garratt, Jemma, Narendra, Tanaya, Vincent, Anna, Jones, Celine, Child, Tim, Coward, Kevin, Graham, Chris, Fritzsche, Marco, Lu, Xin, Srinivas, Shankar
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 17.02.2022 Nature Publishing Group Nature Portfolio
Predmet:	13/100 13/51 14/34 14/63 38/35 631/136/1660 631/80/128/1276 631/80/641 631/80/85/2361 64/110 9/10 96/106 Actin Actin Cytoskeleton - metabolism Animals Apoptosis Regulatory Proteins - metabolism Caco-2 Cells Cell Polarity Context Cytoskeleton Delamination Dogs Embryo Culture Techniques Embryo, Mammalian Epithelium Epithelium - growth & development Epithelium - metabolism Female Gastrulation Germ Layers Humanities and Social Sciences Humans Integrity Madin Darby Canine Kidney Cells Mice Mice, Transgenic Morphogenesis multidisciplinary Mutation Primitive Streak Receptors, Neuropeptide Y - metabolism Science Science (multidisciplinary) Somites Stress, Mechanical Tight Junctions - metabolism Tumor suppressor genes Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Tumors
ISSN:	2041-1723, 2041-1723
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Shrnutí:	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. The early embryo maintains its structure in the face of large mechanical stresses during morphogenesis. Here they show that ASPP2 acts to preserve epithelial integrity in regions of high apical tension during early development.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-022-28590-4