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.
Highlights
During development, pseudostratified epithelia undergo large scale morphogenetic events associated with increased mechanical stress
Our study unveils a central role for ASPP2 in maintaining the integrity of pseudostratified epithelia under increased mechanical stress during major morphogenetic events: in the forming proamniotic cavity, in the primitive streak during gastrulation, in somites and in the head fold region
Though it is required across a diverse range of epithelia, ASPP2 is not required in all epithelia it is expressed during early mouse embryonic development
Summary
During development, pseudostratified epithelia undergo large scale morphogenetic events associated with increased mechanical stress. During development, pseudostratified epithelia are subject to largescale morphogenetic events that dramatically affect their shape and structural organisation This is true during gastrulation in the mouse embryo when cells apically constrict in the primitive streak as they push their cell body basally to eventually delaminate into the underlying mesoderm cell layer[4,5,6,7], or when the ectoderm is reshaped to form the head folds. Such morphogenesis is inextricably linked to mechanical stress (both compressive and tensile), the forces applied to the unit area to produce a change in the shape, volume or length of a cell, tissue or structure[8]. It remains unknown how components of the apicalbasal polarity machinery maintain tissue integrity in conditions of increased mechanical stress as morphogenetic events occur
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