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dc.contributor.authorRayon, Teresa 
dc.contributor.authorMenchero, Sergio 
dc.contributor.authorRollan, Isabel 
dc.contributor.authorOrs, Inmaculada 
dc.contributor.authorHelness, Anne
dc.contributor.authorCrespo, Miguel 
dc.contributor.authorNieto, Andres
dc.contributor.authorAzuara, Veronique
dc.contributor.authorRossant, Janet
dc.contributor.authorManzanares, Miguel 
dc.date.accessioned2017-10-30T13:15:44Z
dc.date.available2017-10-30T13:15:44Z
dc.date.issued2016
dc.identifierISI:000377006800001
dc.identifier.citationSci Rep. 2016; 6:27139
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5223
dc.description.abstractThe first intercellular differences during mammalian embryogenesis arise in the blastocyst, producing the inner cell mass and the trophectoderm. The trophectoderm is the first extraembryonic tissue and does not contribute to the embryo proper, its differentiation instead forming tissues that sustain embryonic development. Crucial roles in extraembryonic differentiation have been identified for certain transcription factors, but a comprehensive picture of the regulation of this early specification is still lacking. Here, we investigated whether the regulatory mechanisms involved in Cdx2 expression in the blastocyst are also utilized in the postimplantation embryo. We analyzed an enhancer that is regulated through Hippo and Notch in the blastocyst trophectoderm, unexpectedly finding that it is inactive in the extraembryonic structures at postimplantation stages. Further analysis identified other Cdx2 regulatory elements including a stem-cell specific regulatory sequence and an element that drives reporter expression in the trophectoderm, a subset of cells in the extraembryonic region of the postimplantation embryo and in trophoblast stem cells. The cross-comparison in this study of cis-regulatory elements employed in the blastocyst, stem cell populations and the postimplantation embryo provides new insights into early mammalian development and suggests a two-step mechanism in Cdx2 regulation.
dc.description.sponsorshipWe thank Barbara Pernaute for comments and suggestions; members of the Manzanares lab for comments, technical help and support; Ian Chambers and Austin Smith for the ZHBTc4 ES cell line; Tristan Rodriguez for the B1-TS cell line; Luis Miguel Criado and the CNIC Transgenesis Unit for TS cell morulae injections and support; Roisin Doohan for help with sections; and Simon Bartlett (CNIC) for English editing. This study was funded by grants from the Ministerio de Economia y Competitividad (grant BFU2011-23083 and BFU2014-54608-P to MM; FPU Doctoral Fellowship to TR; FPI-SO Doctoral Fellowship to SM; Severo Ochoa Center of Excellence award SEV-2015-0505 to CNIC), Comunidad Autonoma de Madrid (grant CELLDD-CM to MM), Canadian Institute of Health Research (JR), Imperial College (VA), and the MRC and Genesis Research Trust (AH). The CNIC is supported by the Spanish Ministerio de Economia y Competitividad and the Pro-CNIC Foundation.
dc.language.isoeng
dc.publisherNature Publishing Group 
dc.type.hasVersionVoR
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectMOUSE BLASTOCYST
dc.subjectTROPHECTODERM
dc.subjectLINEAGE
dc.subjectSPECIFICATION
dc.subjectMAINTENANCE
dc.subjectNETWORKS
dc.subjectEMBRYO
dc.subjectTEAD4
dc.subjectDIFFERENTIATION
dc.subjectCONVERSION
dc.titleDistinct mechanisms regulate Cdx2 expression in the blastocyst and in trophoblast stem cells
dc.typejournal article
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID27256674
dc.format.volume6
dc.identifier.doi10.1038/srep27139
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderCanadian Institutes of Health Research 
dc.contributor.funderImperial College London (Reino Unido) 
dc.contributor.funderMedical Research Council (Reino Unido) 
dc.contributor.funderFundación ProCNIC 
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1038/srep27139
dc.identifier.journalScientific Reports
dc.repisalud.orgCNICCNIC::Grupos de investigación::Genómica Funcional
dc.repisalud.institucionCNIC
dc.relation.projectIDMINECO/ICTI2013-2016/BFU2014-54608-Pes_ES
dc.relation.projectIDMINECO/ICTI2013-2016/SEV-2015-0505es_ES
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
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