ArticlePLoS biology2013
A positive feedback loop involving Gcm1 and Fzd5 directs chorionic branching morphogenesis in the placenta.
Article in PLoS biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 103 citations in OpenAlex.
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- Gcm1 Orchestrates Lef1 Expression in Folate Deficiency-Induced Neural Tube Defects.Molecular neurobiology · 2025Article
- mScience China. Life sciences · 2025Article
- A roadmap towards targeted differentiation of mouse trophoblast stem cells into cell types of the feto-maternal exchange surface.Stem cell research & therapy · 2025Article
- Feto-placental blood vessel development.Development (Cambridge, England) · 2025Review
- WNT16 from decidual stromal cells orchestrates M2 macrophage polarization via β-catenin signaling and chromatin remodeling at the maternal-fetal interface.Frontiers in immunology · 2025Article
- Vitamin C inactivates c-Jun N-terminal kinase to stabilize heart and neural crest derivatives expressed 1 (Hand1) in regulating placentation and maintenance of pregnancy.Cellular and molecular life sciences : CMLS · 2024Article
- TFEB safeguards trophoblast syncytialization in humans and mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The GPI-anchor biosynthesis pathway is critical for syncytiotrophoblast differentiation and placental development.Cellular and molecular life sciences : CMLS · 2024Article
- Species-Specific Transcription Factors Associated with Long Terminal Repeat Promoters of Endogenous Retroviruses: A Comprehensive Review.Biomolecules · 2024Review
- CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- SLC20a1/PiT-1 is required for chorioallantoic placental morphogenesis.Vascular biology (Bristol, England) · 2023Article
- A differentiation roadmap of murine placentation at single-cell resolution.Cell discovery · 2023Article
- Regulators involved in trophoblast syncytialization in the placenta of intrauterine growth restriction.Frontiers in endocrinology · 2023Review
- Maternal anxiety affects embryo implantation via impairing adrenergic receptor signaling in decidual cells.Communications biology · 2022Article
- Primary specification of blastocyst trophectoderm by scRNA-seq: New insights into embryo implantation.Science advances · 2022Article
- P38α MAPK is a gatekeeper of uterine progesterone responsiveness at peri-implantation via Ube3c-mediated PGR degradation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- How trophoblasts fuse: an in-depth look into placental syncytiotrophoblast formation.Cellular and molecular life sciences : CMLS · 2022Review
- NRF2 Serves a Critical Role in Regulation of Immune Checkpoint Proteins (ICPs) During Trophoblast Differentiation.Endocrinology · 2022Article
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Authors and funding
18 authors at 3 institutions in 4 countries.
Funding
Abstract
Chorioallantoic branching morphogenesis is a key milestone during placental development, creating the large surface area for nutrient and gas exchange, and is therefore critical for the success of term pregnancy. Several Wnt pathway molecules have been shown to regulate placental development. However, it remains largely unknown how Wnt-Frizzled (Fzd) signaling spatiotemporally interacts with other essential regulators, ensuring chorionic branching morphogenesis and angiogenesis during placental development. Employing global and trophoblast-specific Fzd5-null and Gcm1-deficient mouse models, combining trophoblast stem cell lines and tetraploid aggregation assay, we demonstrate here that an amplifying signaling loop between Gcm1 and Fzd5 is essential for normal initiation of branching in the chorionic plate. While Gcm1 upregulates Fzd5 specifically at sites where branching initiates in the basal chorion, this elevated Fzd5 expression via nuclear β-catenin signaling in turn maintains expression of Gcm1. Moreover, we show that Fzd5-mediated signaling induces the disassociation of cell junctions for branching initiation via downregulating ZO-1, claudin 4, and claudin 7 expressions in trophoblast cells at the base of the chorion. In addition, Fzd5-mediated signaling is also important for upregulation of Vegf expression in chorion trophoblast cells. Finally, we demonstrate that Fzd5-Gcm1 signaling cascade is operative during human trophoblast differentiation. These data indicate that Gcm1 and Fzd5 function in an evolutionary conserved positive feedback loop that regulates trophoblast differentiation and sites of chorionic branching morphogenesis.
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