title: Notch and hippo converge on Cdx2 to specify the trophectoderm lineage in the mouse blastocyst.
abstract: The first lineage choice in mammalian embryogenesis is that between the trophectoderm, which gives rise to the trophoblast of the placenta, and the inner cell mass, from which is derived the embryo proper and the yolk sac. The establishment of these lineages is preceded by the inside-versus-outside positioning of cells in the early embryo and stochastic expression of key transcription factors, which is then resolved into lineage-restricted expression. The regulatory inputs that drive this restriction and how they relate to cell position are largely unknown. Here, we show an unsuspected role of Notch signaling in regulating trophectoderm-specific expression of Cdx2 in cooperation with TEAD4. Notch activity is restricted to outer cells and is able to influence positional allocation of blastomeres, mediating preferential localization to the trophectoderm. Our results show that multiple signaling inputs at preimplantation stages specify the first embryonic lineages.
authors.affiliation: Stem Cell Biology Program, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rayon
authors.affiliation: Stem Cell Biology Program, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Menchero
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
authors.forename: Andres
authors.initials: A
authors.lastname: Nieto
authors.affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Xenopoulos
authors.affiliation: Stem Cell Biology Program, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Crespo
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Katie
authors.initials: K
authors.lastname: Cockburn
authors.affiliation: Stem Cell Biology Program, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Cañon
authors.affiliation: Institute of Molecular Embryology and Genetics, Department of Cell Fate Control, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
authors.forename: Anna-Katerina
authors.initials: AK
authors.lastname: Hadjantonakis
authors.affiliation: Cardiovascular Developmental Biology Program, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: de la Pompa
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
authors.affiliation: Stem Cell Biology Program, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain. Electronic address: mmanzanares@cnic.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Manzanares
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D000071616:CDX2 Transcription Factor; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004475:Ectoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D000090683:Hippo Signaling Pathway; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009124:Muscle Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D000091262:TEA Domain Transcription Factors; C101204:Tead4 protein, mouse; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases