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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Veröffentlicht in:Nature communications Jg. 13; H. 1; S. 941 - 19
Hauptverfasser: 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
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 17.02.2022
Nature Publishing Group
Nature Portfolio
Schlagworte:
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14/34
14/63
38/35
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631/80/128/1276
631/80/641
631/80/85/2361
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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
Online-Zugang:Volltext
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-28590-4