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Nat Commun ; 13(1): 941, 2022 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-35177595

RESUMEN

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.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Epitelio/crecimiento & desarrollo , Morfogénesis , Proteínas Supresoras de Tumor/metabolismo , Citoesqueleto de Actina/metabolismo , Animales , Células CACO-2 , Polaridad Celular , Perros , Técnicas de Cultivo de Embriones , Embrión de Mamíferos , Epitelio/metabolismo , Femenino , Gastrulación , Estratos Germinativos , Humanos , Células de Riñón Canino Madin Darby , Ratones , Ratones Transgénicos , Mutación , Línea Primitiva , Receptores de Neuropéptido Y/metabolismo , Estrés Mecánico , Uniones Estrechas/metabolismo , Proteínas Supresoras de Tumor/genética
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