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dc.contributor.authorZhu, Meng
dc.contributor.authorShahbazi, Marta
dc.contributor.authorMartin, Angel
dc.contributor.authorZhang, Chuanxin
dc.contributor.authorSozen, Berna
dc.contributor.authorBorsos, Mate
dc.contributor.authorMandelbaum, Rachel S
dc.contributor.authorPaulson, Richard J
dc.contributor.authorMole, Matteo A
dc.contributor.authorEsbert, Marga
dc.contributor.authorTitus, Shiny
dc.contributor.authorScott, Richard T
dc.contributor.authorCampbell, Alison
dc.contributor.authorFishel, Simon
dc.contributor.authorGradinaru, Viviana
dc.contributor.authorZhao, Han
dc.contributor.authorWu, Keliang
dc.contributor.authorChen, Zi-Jiang
dc.contributor.authorSeli, Emre
dc.contributor.authorde Los Santos, Maria J
dc.contributor.authorZernicka Goetz, Magdalena
dc.date.accessioned2021-10-29T01:12:07Z
dc.date.available2021-10-29T01:12:07Z
dc.date.issued2021-09-27
dc.identifier.issn2050-084X
dc.identifier.otherPMC8514238
dc.identifier.other34569938
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330019
dc.descriptionFunder: Open Philanthropy Project
dc.descriptionFunder: Curci and Weston Heavens Foundations
dc.descriptionFunder: European molecular biology organisation
dc.description.abstractApico-basal polarization of cells within the embryo is critical for the segregation of distinct lineages during mammalian development. Polarized cells become the trophectoderm (TE), which forms the placenta, and apolar cells become the inner cell mass (ICM), the founding population of the fetus. The cellular and molecular mechanisms leading to polarization of the human embryo and its timing during embryogenesis have remained unknown. Here, we show that human embryo polarization occurs in two steps: it begins with the apical enrichment of F-actin and is followed by the apical accumulation of the PAR complex. This two-step polarization process leads to the formation of an apical domain at the 8-16 cell stage. Using RNA interference, we show that apical domain formation requires Phospholipase C (PLC) signaling, specifically the enzymes PLCB1 and PLCE1, from the eight-cell stage onwards. Finally, we show that although expression of the critical TE differentiation marker GATA3 can be initiated independently of embryo polarization, downregulation of PLCB1 and PLCE1 decreases GATA3 expression through a reduction in the number of polarized cells. Therefore, apical domain formation reinforces a TE fate. The results we present here demonstrate how polarization is triggered to regulate the first lineage segregation in human embryos.
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2050-084X
dc.sourcenlmid: 101579614
dc.subjectCell biology
dc.subjectHuman embryo
dc.subjectPreimplantation
dc.subjectCell polarity
dc.subjectdevelopmental biology
dc.titleHuman embryo polarization requires PLC signaling to mediate trophectoderm specification.
dc.typeArticle
dc.date.updated2021-10-29T01:07:05Z
prism.publicationNameeLife
prism.volume10
dc.identifier.doi10.17863/CAM.77463
rioxxterms.versionofrecord10.7554/elife.65068
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidZhu, Meng [0000-0001-6157-8840]
dc.contributor.orcidShahbazi, Marta [0000-0002-1599-5747]
dc.contributor.orcidGradinaru, Viviana [0000-0001-5868-348X]
dc.contributor.orcidChen, Zi-Jiang [0000-0001-6637-6631]
dc.contributor.orcidSeli, Emre [0000-0001-7464-8203]
dc.contributor.orcidZernicka Goetz, Magdalena [0000-0002-7004-2471]
pubs.funder-project-idWellcome Trust (207415/Z/17/Z)
pubs.funder-project-idNational Key Research and Development Program of China (2018YFC1004000)
pubs.funder-project-idLeverhulme Trust (RPG-2018-085)
pubs.funder-project-idShandong Provincial Key Research and Development Program (2018YFJH0504)
pubs.funder-project-idMedical Research Council (MC_UP_1201/24)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International