During mammalian development, the challenge for the embryo is to override intrinsic cellular plasticity to drive cells to distinct fates. Here, we unveil novel roles for the HIPPO signaling pathway in controlling cell positioning and expression of Sox2, the first marker of pluripotency in the mouse early embryo. We show that maternal and zygotic YAP1 and WWTR1 repress Sox2 while promoting expression of the trophectoderm gene Cdx2 in parallel. Yet, Sox2 is more sensitive than Cdx2 to Yap1/Wwtr1 dosage, leading cells to a state of conflicted cell fate when YAP1/WWTR1 activity is moderate. Remarkably, HIPPO signaling activity resolves conflicted cell fate by repositioning cells to the interior of the embryo, independent of its role in regulating Sox2 expression. Rather, HIPPO antagonizes apical localization of Par complex components PARD6B and aPKC. Thus, negative feedback between HIPPO and Par complex components ensure robust lineage segregation.
Pubmed ID: 30526858 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Commercial antibody vendor which supplies antibodies and other products to life science researchers.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsA commercial antibody vendor, specializing in secondary antibodies.
View all literature mentionsMus musculus with name Crl:CD1(ICR) from IMSR.
View all literature mentionsThis polyclonal targets YAP1
View all literature mentionsThis monoclonal targets Uvomorulin / E-Cadherin
View all literature mentionsThis monoclonal targets YAP (63.7)
View all literature mentionsThis polyclonal targets Green Fluorescent Protein (GFP)
View all literature mentionsThis monoclonal targets ZO-1
View all literature mentionsThis unknown targets PARD6B
View all literature mentionsThis polyclonal targets SOX2
View all literature mentionsThis monoclonal targets CDX-2
View all literature mentionsThis polyclonal targets PARD6B
View all literature mentionsMus musculus with name 129-Alpltm1(cre)Nagy/J from IMSR.
View all literature mentionsSoftware for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionslaboratory mouse with name C57BL/6-Tg(Zp3-cre)93Knw from MGI.
View all literature mentionsMus musculus with name STOCK Sox2tm1.1Lan/J from IMSR.
View all literature mentionsMus musculus with name Crl:CD1(ICR) from IMSR.
View all literature mentions