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Cell Death Dis. 2019 Jun 5;10(6):438. doi: 10.1038/s41419-019-1683-1.

Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis.

Lu J1,2, Wu W3, Xin Q4, Zhou C4, Wang J1,2, Ni Z4, Liu D1,2, Xu Y1,2, Yu Y1,2, Yang N1,2, Sun Y1,2, He B1,2, Kong S1,2, Wang S5, Wang C6, Wang H7,8.

Author information

1
Reproductive Medical Center, The First Affiliated Hospital of Xiamen University, 361003, Xiamen, Fujian, People's Republic of China.
2
Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, 361102, Xiamen, Fujian, People's Republic of China.
3
Anti-aging & Regenerative Medicine Research Institution, College of Life Sciences, Shandong University of Technology, 255049, Zibo, Shandong, People's Republic of China.
4
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, People's Republic of China.
5
National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, 100193, Beijing, People's Republic of China. wangshumin@cau.edu.cn.
6
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, People's Republic of China. wangcam@cau.edu.cn.
7
Reproductive Medical Center, The First Affiliated Hospital of Xiamen University, 361003, Xiamen, Fujian, People's Republic of China. haibin.wang@vip.163.com.
8
Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, 361102, Xiamen, Fujian, People's Republic of China. haibin.wang@vip.163.com.

Abstract

The placenta, responsible for the nutrient and gas exchange between the mother and fetus, is pivotal for successful pregnancy. It has been shown that Rbpj, the core transcriptional mediator of Notch signaling pathway, is required for normal placentation in mice. However, it remains largely unclear how Rbpj signaling in different placental compartments coordinates with other important regulators to ensure normal placental morphogenesis. In this study, we found that systemic deletion of Rbpj led to abnormal chorioallantoic morphogenesis and defective trophoblast differentiation in the ectoplacental cone (EPC). Employing mouse models with selective deletion of Rbpj in the allantois versus trophoblast, combining tetraploid aggregation assay, we demonstrated that allantois-expressed Rbpj is essential for chorioallantoic attachment and subsequent invagination of allantoic blood vessels into the chorionic ectoderm. Further studies uncovered that allantoic Rbpj regulates chorioallantoic fusion and morphogenesis via targeting Vcam1 in a Notch-dependent manner. Meanwhile, we also revealed that trophoblast-expressed Rbpj in EPC facilitates Mash2's transcriptional activity, promoting the specification of Tpbpα-positive trophoblasts, which differentiate into trophoblast subtypes responsible for interstitial and endovascular invasion at the later stage of placental development. Collectively, our study further shed light on the molecular network governing placental development and functions, highlighting the necessity of a spatiotemporal coordination of Rbpj signaling for normal placental morphogenesis.

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