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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / cytology
  • Blastocyst / metabolism*
  • CDX2 Transcription Factor
  • Cell Lineage*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Ectoderm / cytology
  • Ectoderm / embryology
  • Ectoderm / metabolism*
  • Gene Expression Regulation, Developmental
  • HEK293 Cells
  • Hippo Signaling Pathway
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism*
  • TEA Domain Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic

Substances

  • CDX2 Transcription Factor
  • Cdx2 protein, mouse
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Muscle Proteins
  • Notch1 protein, mouse
  • Receptor, Notch1
  • TEA Domain Transcription Factors
  • Tead4 protein, mouse
  • Transcription Factors
  • Protein Serine-Threonine Kinases