Volume 24, No 8, Aug 2014

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 24 Issue 8, August 2014: 925-942   |  Open Access

ORIGINAL ARTICLES

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

Shuang Zhang1,*, Shuangbo Kong1,2,*, Bingyan Wang1, Xiaohong Cheng^1,3, Yongjie Chen^1,2, Weiwei Wu^1,2, Qiang Wang¹, Junchao Shi^1,2, Ying Zhang¹, Shumin Wang¹, Jinhua Lu¹, John P Lydon⁴, Francesco DeMayo⁴, Warren S Pear⁵, Hua Han^6,7, Haiyan Lin¹, Lei Li¹, Hongmei Wang¹, Yan-ling Wang¹, Bing Li³, Qi Chen¹, Enkui Duan¹ and Haibin Wang¹

¹State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
²University of Chinese Academy of Sciences, Beijing 100101, China
³Reproductive Medical Center, The Third Affiliated Hospital of Guangzhou Medical College, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, Guangdong, China
⁴Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
⁵Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
⁶Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi 710032, China
⁷State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, Shanxi 710032, China Correspondence: Haibin Wang, Tel: 86-01-64807868 E-mail: hbwang@ioz.ac.cn; Enkui Duan, Tel: 86-01-64807182 E-mail: duane@ioz.ac.cn; Qi Chen, Tel: 86-01-64807182 (chenqi@ioz.ac.cn)

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.

10.1038/cr.2014.82

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