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.
Highlights
The placenta is vital to the survival and growth of the fetus before birth, since it provides the fetus with nutrients and gases during pregnancy
To further explore the pathophysiological significance of Rbpj signaling during early placental development, we first performed in situ hybridization to examine the spatiotemporal expression profile of Rbpj in extraembryonic tissues
Regardless of the dispensability of Rbpj signaling in chronic trophoblast differentiation, we eventually looked into the significance of Rbpj during ectoplacental cone development, since its expression was persistent in EPC and trophoblast giant cells (TGC) at E8.0–10.5 (Fig. 1a)
Summary
The placenta is vital to the survival and growth of the fetus before birth, since it provides the fetus with nutrients and gases during pregnancy. The glycogen trophoblast cells invade interstitially into maternal decidua and form wrapping layers around spiral arteries[8], contributing to spiral artery dilation[9]. These dynamic cellular events coordinately decrease vascular resistance of spiral arteries, increasing placental perfusion by maternal blood to meet the increasing needs of the fetus[10,11]. It remains largely unknown how these developmental processes are tightly coordinated to guarantee normal development and functions of the placenta
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