ArticlePLoS genetics2014
Vangl2-regulated polarisation of second heart field-derived cells is required for outflow tract lengthening during cardiac development.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 100 citations in OpenAlex.
- Mechanosensitive feedback organizes cell shape and motion during hindbrain neuropore morphogenesis.Current biology : CB · 2026Article
- Neural crest cell-derived DKK1 and NEDD4 modulate Wnt signalling in the second heart field to orchestrate outflow tract development.Nature communications · 2026Article
- Modelling Tetralogy of Fallot: insights and limitations of animal models.Frontiers in cell and developmental biology · 2026Review
- Osr1 orchestrates posterior second heart field cell migration for outflow tract formation.Communications biology · 2025Article
- Immune-mediated cardiac development and regeneration.Seminars in cell & developmental biology · 2025Review
- Zebrafish arterial valve development occurs through direct differentiation of second heart field progenitors.Cardiovascular research · 2025Article
- Mesodermal fibronectin controls cell shape, polarity, and mechanotransduction in the second heart field during cardiac outflow tract development.Developmental cell · 2025Article
- Single-cell morphometrics reveals T-box gene-dependent patterns of epithelial tension in the Second Heart field.Nature communications · 2024Article
- Loss of the endoplasmic reticulum protein Tmem208 affects cell polarity, development, and viability.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Functional analysis of germline VANGL2 variants using rescue assays of vangl2 knockout zebrafish.Human molecular genetics · 2024Article
- Molecular Pathways and Animal Models of Tetralogy of Fallot and Double Outlet Right Ventricle.Advances in experimental medicine and biology · 2024Review
- Human Cardiac Development.Advances in experimental medicine and biology · 2024Article
- Cardiac Progenitor Cells of the First and Second Heart Fields.Advances in experimental medicine and biology · 2024Article
- A method for TAT-Cre recombinase-mediated floxed allele modification in ex vivo tissue slices.Disease models & mechanisms · 2023Article
- EZH2 controls epicardial cell migration during heart development.Life science alliance · 2023Article
- The second heart field: the first 20 years.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Multiomics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and noncanonical Wnt signaling dysregulation.JCI insight · 2023Article
- A pictorial account of the human embryonic heart between 3.5 and 8 weeks of development.Communications biology · 2022Article
- Protocols for Investigating the Epithelial Properties of Cardiac Progenitor Cells in the Mouse Embryo.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Vangl2-environment interaction causes severe neural tube defects, without abnormal neuroepithelial convergent extension.Disease models & mechanisms · 2022Article
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Authors and funding
9 authors at 3 institutions in 1 country.
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Abstract
Planar cell polarity (PCP) is the mechanism by which cells orient themselves in the plane of an epithelium or during directed cell migration, and is regulated by a highly conserved signalling pathway. Mutations in the PCP gene Vangl2, as well as in other key components of the pathway, cause a spectrum of cardiac outflow tract defects. However, it is unclear why cells within the mesodermal heart tissue require PCP signalling. Using a new conditionally floxed allele we show that Vangl2 is required solely within the second heart field (SHF) to direct normal outflow tract lengthening, a process that is required for septation and normal alignment of the aorta and pulmonary trunk with the ventricular chambers. Analysis of a range of markers of polarised epithelial tissues showed that in the normal heart, undifferentiated SHF cells move from the dorsal pericardial wall into the distal outflow tract where they acquire an epithelial phenotype, before moving proximally where they differentiate into cardiomyocytes. Thus there is a transition zone in the distal outflow tract where SHF cells become more polarised, turn off progenitor markers and start to differentiate to cardiomyocytes. Membrane-bound Vangl2 marks the proximal extent of this transition zone and in the absence of Vangl2, the SHF-derived cells are abnormally polarised and disorganised. The consequent thickening, rather than lengthening, of the outflow wall leads to a shortened outflow tract. Premature down regulation of the SHF-progenitor marker Isl1 in the mutants, and accompanied premature differentiation to cardiomyocytes, suggests that the organisation of the cells within the transition zone is important for maintaining the undifferentiated phenotype. Thus, Vangl2-regulated polarisation and subsequent acquisition of an epithelial phenotype is essential to lengthen the tubular outflow vessel, a process that is essential for on-going cardiac morphogenesis.
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