Uterine Rbpj is required for embryonic-uterine orientation and decidual remodeling via Notch pathway-independent and -dependent mechanisms

Cell Res. 2014 Aug;24(8):925-42. doi: 10.1038/cr.2014.82. Epub 2014 Jun 27.

Abstract

Coordinated uterine-embryonic axis formation and decidual remodeling are hallmarks of mammalian post-implantation embryo development. Embryonic-uterine orientation is determined at initial implantation and synchronized with decidual development. However, the molecular mechanisms controlling these events remain elusive despite its discovery a long time ago. In the present study, we found that uterine-specific deletion of Rbpj, the nuclear transducer of Notch signaling, resulted in abnormal embryonic-uterine orientation and decidual patterning at post-implantation stages, leading to substantial embryo loss. We further revealed that prior to embryo attachment, Rbpj confers on-time uterine lumen shape transformation via physically interacting with uterine estrogen receptor (ERα) in a Notch pathway-independent manner, which is essential for the initial establishment of embryo orientation in alignment with uterine axis. While at post-implantation stages, Rbpj directly regulates the expression of uterine matrix metalloproteinase in a Notch pathway-dependent manner, which is required for normal post-implantation decidual remodeling. These results demonstrate that uterine Rbpj is essential for normal embryo development via instructing the initial embryonic-uterine orientation and ensuring normal decidual patterning in a stage-specific manner. Our data also substantiate the concept that normal mammalian embryonic-uterine orientation requires proper guidance from developmentally controlled uterine signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryo Implantation
  • Embryo, Mammalian / physiology
  • Embryonic Development
  • Estrogen Receptor alpha / metabolism
  • Female
  • HEK293 Cells
  • Humans
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / genetics
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism*
  • Male
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Transgenic
  • Receptors, Notch / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Uterus / metabolism*
  • Uterus / pathology

Substances

  • Estrogen Receptor alpha
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Rbpj protein, mouse
  • Receptors, Notch
  • Transcription Factors
  • Matrix Metalloproteinases