ArticleDevelopmental dynamics : an official publication of the American Association of Anatomists2019
Tmem2 restricts atrioventricular canal differentiation by regulating degradation of hyaluronic acid.
Article in Developmental dynamics : an official publication of the American Association of Anatomists, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Hyaluronan in cardiac disease: implications for the extracellular matrix beyond collagen.American journal of physiology. Heart and circulatory physiology · 2026Review
- Regionalized regulation of actomyosin organization influences cardiomyocyte cell shape changes during chamber curvature formation.Nature communications · 2026Article
- Genetic Deficiencies of Hyaluronan Degradation.Cells · 2024Review
- Mechanical forces remodel the cardiac extracellular matrix during zebrafish development.Development (Cambridge, England) · 2024Article
- 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
- Structure of the transmembrane protein 2 (TMEM2) ectodomain and its apparent lack of hyaluronidase activity.Wellcome open research · 2023Article
- Zebrafish Models in Therapeutic Research of Cardiac Conduction Disease.Frontiers in cell and developmental biology · 2021Review
- Epithelial-Mesenchymal Transition: Role in Cancer Progression and the Perspectives of Antitumor Treatment.Acta naturaeArticle
- TMEM2: A New Dimension in Hyaluronan Biology.Proteoglycan researchArticle
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
backgroundAtrioventricular valve development relies upon the precisely defined dimensions of the atrioventricular canal (AVC). Current models suggest that Wnt signaling plays an important role atop a pathway that promotes AVC development. The factors that confine AVC differentiation to the appropriate location, however, are less well understood.
resultsTransmembrane protein 2 (Tmem2) is a key player in restricting AVC differentiation: in zebrafish, tmem2 mutants display an expansion of AVC characteristics, but the molecular mechanism of Tmem2 function in this context remains unclear. Through structure-function analysis, we demonstrate that the extracellular portion of Tmem2 is crucial for its role in restricting AVC boundaries. Importantly, the Tmem2 ectodomain contains regions implicated in the depolymerization of hyaluronic acid (HA). We find that tmem2 mutant hearts exhibit excess HA deposition alongside broadened distribution of Wnt signaling. Moreover, addition of ectopic hyaluronidase can restore the restriction of AVC differentiation in tmem2 mutants. Finally, we show that alteration of a residue important for HA depolymerization impairs the efficacy of Tmem2 function during AVC development.
conclusionsTaken together, our data support a model in which HA degradation, regulated by Tmem2, limits the distribution of Wnt signaling and thereby confines the differentiation of the AVC.
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