Coward, K. | Search bioRxiv

bioRxiv2020

ASPP2/PP1 complexes maintain the integrity of pseudostratified epithelia undergoing remodelling during morphogenesis

During development, pseudostratified epithelia undergo large scale morphogenetic events associated with increased mechanical stress. The molecular mechanisms that maintain tissue integrity in this context are poorly understood. Using a variety of genetic and imaging approaches, we uncover that the ASPP2/PP1 complex ensures proper epiblast and proamniotic cavity architecture via a mechanism that specifically prevents the most apical daughter cells from delaminating apically following cell division events. The ASPP2/PP1 complex achieves this by maintaining the integrity and organisation of the F-actin cytoskeleton at the apical surface of dividing cells. ASPP2/PP1 is also essential during gastrulation in the primitive streak, in somites and in the head fold region, suggesting that this complex is required across a wide range of pseudostratified epithelia during morphogenetic events that are accompanied by intense tissue remodelling and high cell proliferation. 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.

developmental biology↗

bioRxiv2019

Position-sensing established duringcompaction dictates cell fate in themammalian embryo

Precise patterning within the 3-dimensional context of tissues, organs and embryos implies that cells can sense their relative position. We still understand relatively little about how cells sense their relative position within small groups of cells. During preimplantation development, outside and inside cells rely on apicobasal polarity and the Hippo pathway to choose their fate. Despite recent findings suggesting that mechanosensing may be central to this process, the relationship between blastomere geometry (i.e. shape and position) and the Hippo pathway effector YAP remains unknown. To address this, we used a highly quantitative approach to collect and analyse information on the geometry and YAP localisation of individual blastomeres of mouse and human embryos. We find that the fraction of YAP in the nucleus responds to the proportion of exposed cell surface area rather than blastomere shape. To directly test the influence of blastomere position on YAP localisation we developed an approach using hydrogel based cylindrical cavities to alter blastomere arrangement in cultured embryos. Unbiased clustering analyses of blastomeres from such embryos reveal that the ability to respond to position emerges as early as the 8-cell stage during compaction and that altering the relative position of a blastomere within an embryo can alter its fate. Finally, we demonstrate that this response is lost upon inhibiting PKC signalling, linking it to the cell polarity. Our results pinpoint when during early embryogenesis cell specification decisions are initiated and show how blastomeres can sense their position in a polarity dependent manner to alter YAP localisation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/856161v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@845b46org.highwire.dtl.DTLVardef@18473ceorg.highwire.dtl.DTLVardef@cf0124org.highwire.dtl.DTLVardef@53fc8b_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗