ArticleDevelopment (Cambridge, England)2015
A Grhl2-dependent gene network controls trophoblast branching morphogenesis.
Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 86 citations in OpenAlex.
- Defining the DNA Binding Specificity of GRHL2.bioRxiv : the preprint server for biology · 2026Article
- Membrane-Anchored Serine Protease Inhibitors: Physiological Functions, Mechanisms, and Roles in Cancer.International journal of molecular sciences · 2026Review
- Association Analysis of SNPs inAnimals : an open access journal from MDPI · 2025Article
- GRHL2 suppression of NT5E/CD73 in breast cancer cells modulates CD73-mediated adenosine production and T cell recruitment.iScience · 2024Article
- Complex regulatory networks influence pluripotent cell state transitions in human iPSCs.Nature communications · 2024Article
- A non-coding insertional mutation of Grhl2 causes gene over-expression and multiple structural anomalies including cleft palate, spina bifida and encephalocele.Human molecular genetics · 2023Article
- Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells.Genome research · 2023Article
- GRHL2 Regulation of Growth/Motility Balance in Luminal versus Basal Breast Cancer.International journal of molecular sciences · 2023Article
- GRHL2-controlled gene expression networks in luminal breast cancer.Cell communication and signaling : CCS · 2023Article
- Grainyhead-like 2 is required for morphological integrity of mouse embryonic stem cells and orderly formation of inner ear-like organoids.Frontiers in cell and developmental biology · 2023Article
- GRHL2 Enhances Phosphorylated Estrogen Receptor (ER) Chromatin Binding and Regulates ER-Mediated Transcriptional Activation and Repression.Molecular and cellular biology · 2022Article
- Grainyhead-like (Grhl) Target Genes in Development and Cancer.International journal of molecular sciences · 2022Review
- Identification of photoperiod-induced specific miRNAs in the adrenal glands of Sunite sheep (Frontiers in veterinary science · 2022Article
- Article
- Expression of Grainyhead-like 2 in the Process of Ductal Development of Mouse Mammary Gland.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021Article
- The Hippo pathway component Wwc2 is a key regulator of embryonic development and angiogenesis in mice.Cell death & disease · 2021Article
- Article
- Article
- MEDEA: analysis of transcription factor binding motifs in accessible chromatin.Genome research · 2020Article
- Inactivation ofDisease models & mechanisms · 2020Article
Corrections and comments
- Commented on by
Authors and funding
20 authors at 7 institutions in 3 countries.
Funding
Abstract
Healthy placental development is essential for reproductive success; failure of the feto-maternal interface results in pre-eclampsia and intrauterine growth retardation. We found that grainyhead-like 2 (GRHL2), a CP2-type transcription factor, is highly expressed in chorionic trophoblast cells, including basal chorionic trophoblast (BCT) cells located at the chorioallantoic interface in murine placentas. Placentas from Grhl2-deficient mouse embryos displayed defects in BCT cell polarity and basement membrane integrity at the chorioallantoic interface, as well as a severe disruption of labyrinth branching morphogenesis. Selective Grhl2 inactivation only in epiblast-derived cells rescued all placental defects but phenocopied intraembryonic defects observed in global Grhl2 deficiency, implying the importance of Grhl2 activity in trophectoderm-derived cells. ChIP-seq identified 5282 GRHL2 binding sites in placental tissue. By integrating these data with placental gene expression profiles, we identified direct and indirect Grhl2 targets and found a marked enrichment of GRHL2 binding adjacent to genes downregulated in Grhl2(-/-) placentas, which encoded known regulators of placental development and epithelial morphogenesis. These genes included that encoding the serine protease inhibitor Kunitz type 1 (Spint1), which regulates BCT cell integrity and labyrinth formation. In human placenta, we found that human orthologs of murine GRHL2 and its targets displayed co-regulation and were expressed in trophoblast cells in a similar domain as in mouse placenta. Our data indicate that a conserved Grhl2-coordinated gene network controls trophoblast branching morphogenesis, thereby facilitating development of the site of feto-maternal exchange. This might have implications for syndromes related to placental dysfunction.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.