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Sequential formation and resolution of multiple rosettes drive embryo remodelling after implantation

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Christodoulou, N 
Kyprianou, Christos 
Wang, Ran 
Cui, Guizhong 


The morphogenetic remodelling of embryo architecture after implantation culminates in pro-amniotic cavity formation. Despite its key importance, how this transformation occurs remains unknown. Here, we apply high-resolution imaging of embryos developing in vivo and in vitro, spatial RNA sequencing and 3D trophoblast stem cell models to determine the sequence and mechanisms of these remodelling events. We show that cavitation of the embryonic tissue is followed by folding of extra-embryonic tissue to mediate the formation of a second extra-embryonic cavity. Concomitantly, at the boundary between embryonic and extra-embryonic tissues, a hybrid 3D rosette forms. Resolution of this rosette enables the embryonic cavity to invade the extra-embryonic tissue. Subsequently, β1-integrin signalling mediates the formation of multiple extra-embryonic 3D rosettes. Podocalyxin exocytosis leads to their polarized resolution, permitting the extension of embryonic and extra-embryonic cavities and their fusion into a unified pro-amniotic cavity. These morphogenetic transformations of embryogenesis reveal a previously unappreciated mechanism for lumen expansion and fusion



Animals, Cells, Cultured, Embryo, Mammalian, Female, Gene Expression Profiling, Gene Expression Regulation, Developmental, Male, Mice, Transgenic, Microscopy, Confocal, Morphogenesis, Stem Cells, Trophoblasts

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Nature Cell Biology

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Springer Nature
Wellcome Trust (098287/Z/12/Z)
European Research Council (669198)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (721537)
BBSRC (1497839)
The M.Z.G lab is supported by grants from the European Research Council (669198) and the Welcome Trust (098287/Z/12/Z) and the EU Horizon 2020 Marie Sklodowska-Curie actions (ImageInLife,721537). C.K is supported by BBSRC Doctoral training studentship.