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Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis
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 h...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549187/ https://www.ncbi.nlm.nih.gov/pubmed/31165749 http://dx.doi.org/10.1038/s41419-019-1683-1 |
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author | Lu, Jinhua Wu, Weiwei Xin, Qiliang Zhou, Chan Wang, Jianqi Ni, Zhangli Liu, Dong Xu, Yingchun Yu, Yongqin Yang, Ningjie Sun, Yang He, Bo Kong, Shuangbo Wang, Shumin Wang, Chao Wang, Haibin |
author_facet | Lu, Jinhua Wu, Weiwei Xin, Qiliang Zhou, Chan Wang, Jianqi Ni, Zhangli Liu, Dong Xu, Yingchun Yu, Yongqin Yang, Ningjie Sun, Yang He, Bo Kong, Shuangbo Wang, Shumin Wang, Chao Wang, Haibin |
author_sort | Lu, Jinhua |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6549187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65491872019-06-17 Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis Lu, Jinhua Wu, Weiwei Xin, Qiliang Zhou, Chan Wang, Jianqi Ni, Zhangli Liu, Dong Xu, Yingchun Yu, Yongqin Yang, Ningjie Sun, Yang He, Bo Kong, Shuangbo Wang, Shumin Wang, Chao Wang, Haibin Cell Death Dis Article 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. Nature Publishing Group UK 2019-06-05 /pmc/articles/PMC6549187/ /pubmed/31165749 http://dx.doi.org/10.1038/s41419-019-1683-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Lu, Jinhua Wu, Weiwei Xin, Qiliang Zhou, Chan Wang, Jianqi Ni, Zhangli Liu, Dong Xu, Yingchun Yu, Yongqin Yang, Ningjie Sun, Yang He, Bo Kong, Shuangbo Wang, Shumin Wang, Chao Wang, Haibin Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis |
title | Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis |
title_full | Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis |
title_fullStr | Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis |
title_full_unstemmed | Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis |
title_short | Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis |
title_sort | spatiotemporal coordination of trophoblast and allantoic rbpj signaling directs normal placental morphogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549187/ https://www.ncbi.nlm.nih.gov/pubmed/31165749 http://dx.doi.org/10.1038/s41419-019-1683-1 |
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