Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis
Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis
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滋养层和尿囊 Rbpj 信号的时空协调指导正常胎盘形态发生
DOI：
10.1038/s41419-019-1683-1
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发表时间：
2019-06-05
影响因子：
9
通讯作者：
Wang, Haibin
中科院分区：
文献类型：
--
作者：
Lu, Jinhua;Wu, Weiwei;Wang, Haibin
胎盘负责母亲和胎儿之间的营养和气体交换，是成功怀孕的关键。研究表明，Notch信号通路的核心转录介质Rbpj是小鼠正常胎盘形成所必需的。然而，在很大程度上仍然不清楚Rbpj信号在不同的胎盘隔室协调与其他重要的监管机构，以确保正常的胎盘形态发生。在这项研究中，我们发现，系统性缺失Rbpj导致异常的绒毛尿囊形态发生和缺陷的滋养细胞分化的外胎盘锥（EPC）。采用选择性缺失Rbpj的小鼠模型，结合四倍体聚集试验，我们证明了尿囊表达的Rbpj对于绒毛膜尿囊附着和随后的尿囊血管内陷到绒毛膜外胚层中是必不可少的。进一步的研究发现，尿囊素Rbpj以Notch依赖的方式通过靶向Vcam 1调控绒毛尿囊膜融合和形态发生。同时，我们还发现，滋养层细胞在EPC中表达Rbpj促进Mash 2的转录活性，促进Tpbp α阳性滋养层细胞的特化，这些滋养层细胞分化为滋养层细胞亚型，负责胎盘发育后期的间质和血管内侵袭。总的来说，我们的研究进一步阐明了控制胎盘发育和功能的分子网络，突出了Rbpj信号传导对正常胎盘形态发生的时空协调的必要性。
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 ofRbpjled to abnormal chorioallantoic morphogenesis and defective trophoblast differentiation in the ectoplacental cone (EPC). Employing mouse models with selective deletion ofRbpjin 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 targetingVcam1in a Notch-dependent manner. Meanwhile, we also revealed that trophoblast-expressed Rbpj in EPC facilitates Mash2’s transcriptional activity, promoting the specification ofTpbpα-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.