Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK.
Nat Commun. 2022 Feb 17;13(1):941. doi: 10.1038/s41467-022-28590-4.
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.
在发育过程中，假复层上皮经历与机械应力增加相关的大规模形态发生事件。通过使用各种遗传和成像方法，我们发现，在 E6.5 期小鼠的外胚层中，顶端张力最高，ASPP2 可保护组织完整性。它通过防止最顶端的子细胞在分裂事件后从顶端分离来实现这一点。在这种情况下，ASPP2 维持顶端连接处丝状肌动蛋白细胞骨架的完整性和组织。ASPP2 在原条、体节和头部褶皱区域的原肠胚形成期间也是必需的，这表明它在伴随着强烈组织重塑的形态发生事件期间在广泛的假复层上皮中是必需的。最后，我们的研究还表明，ASPP2 与 PP1 之间的相互作用对 ASPP2 的肿瘤抑制功能至关重要，这在易受机械应力增加影响的组织中可能尤为重要。
