ArticleDevelopment (Cambridge, England)2016
Wnt/β-catenin signaling enables developmental transitions during valvulogenesis.
Article in Development (Cambridge, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
What it found
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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
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Genome and Transcriptome-Wide Analyses Identify Multiple Candidate Genes and a Significant Polygenic Contribution in Bicuspid Aortic Valve.Circulation · 2026Pooled it
- Pooled it
- Novel mutations of AXIN2 identified in a Chinese Congenital Heart Disease Cohort.Journal of human genetics · 2019Trial
- Hyaluronan in cardiac disease: implications for the extracellular matrix beyond collagen.American journal of physiology. Heart and circulatory physiology · 2026Review
- Cardiac EndMT and EpiMT as a developmental continuum: integration of mechanical, metabolic, and epigenetic regulation.Frontiers in cell and developmental biology · 2026Review
- Wnt Signaling Inhibition Prevents Postnatal Inflammation and Disease Progression in Mouse Congenital Myxomatous Valve Disease.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Elucidating the crosstalk between endothelial-to-mesenchymal transition (EndoMT) and endothelial autophagy in the pathogenesis of atherosclerosis.Vascular pharmacology · 2024Review
- Zebrafish smarcc1a mutants reveal requirements for BAF chromatin remodeling complexes in distinguishing the atrioventricular canal from the cardiac chambers.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Article
- β-Catenin regulates endocardial cushion growth by suppressing p21.Life science alliance · 2023Article
- Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.International journal of molecular sciences · 2023Review
- An Overview of Epithelial-to-Mesenchymal Transition and Mesenchymal-to-Epithelial Transition in Canine Tumors: How Far Have We Come?Veterinary sciences · 2022Review
- Wnt Signaling in Heart Development and Regeneration.Current cardiology reports · 2022Review
- Wnt Site Signaling Inhibitor Secreted Frizzled-Related Protein 3 Protects Mitral Valve Endothelium From Myocardial Infarction-Induced Endothelial-to-Mesenchymal Transition.Journal of the American Heart Association · 2022Article
- Post-Transcriptional Regulation of Molecular Determinants during Cardiogenesis.International journal of molecular sciences · 2022Review
- Local fluid shear stress operates a molecular switch to drive fetal semilunar valve extension.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- DZIP1 regulates mammalian cardiac valve development through a Cby1-β-catenin mechanism.Developmental dynamics : an official publication of the American Association of Anatomists · 2021Article
- Stationed or Relocating: The Seesawing EMT/MET Determinants from Embryonic Development to Cancer Metastasis.Biomedicines · 2021Review
- Spermine Protects Cardiomyocytes from High Glucose-Induced Energy Disturbance by Targeting the CaSR-gp78-Ubiquitin Proteasome System.Cardiovascular drugs and therapy · 2021Article
- Genetic and epigenetic mechanisms in the development of congenital heart diseases.World journal of pediatric surgery · 2021Review
- A Genomic Study of Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels.Animals : an open access journal from MDPI · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Heart valve development proceeds through coordinated steps by which endocardial cushions (ECs) form thin, elongated and stratified valves. Wnt signaling and its canonical effector β-catenin are proposed to contribute to endocardial-to-mesenchymal transformation (EMT) through postnatal steps of valvulogenesis. However, genetic redundancy and lethality have made it challenging to define specific roles of the canonical Wnt pathway at different stages of valve formation. We developed a transgenic mouse system that provides spatiotemporal inhibition of Wnt/β-catenin signaling by chemically inducible overexpression of Dkk1. Unexpectedly, this approach indicates canonical Wnt signaling is required for EMT in the proximal outflow tract (pOFT) but not atrioventricular canal (AVC) cushions. Furthermore, Wnt indirectly promotes pOFT EMT through its earlier activity in neighboring myocardial cells or their progenitors. Subsequently, Wnt/β-catenin signaling is activated in cushion mesenchymal cells where it supports FGF-driven expansion of ECs and then AVC valve extracellular matrix patterning. Mice lacking Axin2, a negative Wnt regulator, have larger valves, suggesting that accumulating Axin2 in maturing valves represents negative feedback that restrains tissue overgrowth rather than simply reporting Wnt activity. Disruption of these Wnt/β-catenin signaling roles that enable developmental transitions during valvulogenesis could account for common congenital valve defects.
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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.