Figure 7.

Illustrative model of uterine Rbpj's role during the peri-implantation period for embryo development. In normal situation (left), the embryonic axis is consistent with the uterine M-AM axis. In uteri containing a specific deletion of Rbpj (right), the process of uterine luminal closure is defective during the pre-implantation period, leading to the formation of extra epithelial folds that “trap” the implanting blastocyst, which is caused by unleashed ERα activity due to the loss of physical interaction of Rbpj and ERα(Notch pathway-independent). After the blastocyst establishes the embryonic axis in an abnormal uterine fold, the development of the embryonic axis will deflect from the uterine axis. During post-implantation development, the loss of Rbpj results in abnormal decidual patterning due to decreased Mmp2 expression that is transcriptionally regulated by Rbpj (Notch pathway-dependent). The combined defects in uterine-embryonic orientation and decidual patterning in Rbpj^d/d mice lead to subsequent embryonic lethality.