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Dev Cell. 2014 Aug 25;30(4):410-22. doi: 10.1016/j.devcel.2014.06.019. Epub 2014 Aug 7.

Notch and hippo converge on Cdx2 to specify the trophectoderm lineage in the mouse blastocyst.

Author information

1
Stem Cell Biology Program, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
2
Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
3
Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
4
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.
5
Institute of Molecular Embryology and Genetics, Department of Cell Fate Control, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
6
Cardiovascular Developmental Biology Program, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
7
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.

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.

PMID:
25127056
PMCID:
PMC4146744
DOI:
10.1016/j.devcel.2014.06.019
[Indexed for MEDLINE]
Free PMC Article

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