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ASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis.
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.
Afiliación
  • Royer C; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK. christophe.royer@dpag.ox.ac.uk.
  • Sandham E; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
  • Slee E; Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK.
  • Schneider F; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Lagerholm CB; Translational Imaging Center, University of Southern California, Los Angeles, CA, 90089, USA.
  • Godwin J; Wolfson Imaging Centre Oxford, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Veits N; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
  • Hathrell H; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
  • Zhou F; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
  • Leonavicius K; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
  • Garratt J; Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK.
  • Narendra T; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
  • Vincent A; Institute of Biotechnology, Vilnius University, Vilnius, Lithuania.
  • Jones C; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
  • Child T; Nuffield Department of Women's and Reproductive Health, University of Oxford, Level 3, Women's Centre, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
  • Coward K; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
  • Graham C; Nuffield Department of Women's and Reproductive Health, University of Oxford, Level 3, Women's Centre, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
  • Fritzsche M; Oxford Fertility, Institute of Reproductive Sciences, Oxford Business Park North, Oxford, OX4 2HW, UK.
  • Lu X; Nuffield Department of Women's and Reproductive Health, University of Oxford, Level 3, Women's Centre, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
  • Srinivas S; Nuffield Department of Women's and Reproductive Health, University of Oxford, Level 3, Women's Centre, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
Nat Commun ; 13(1): 941, 2022 02 17.
Article en En | MEDLINE | ID: mdl-35177595
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Supresoras de Tumor / Epitelio / Proteínas Reguladoras de la Apoptosis / Morfogénesis Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Supresoras de Tumor / Epitelio / Proteínas Reguladoras de la Apoptosis / Morfogénesis Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido