ArticleCardiovascular research2022
Asymmetric Hapln1a drives regionalized cardiac ECM expansion and promotes heart morphogenesis in zebrafish development.
Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- ALPK3 regulates cardiomyocyte apoptosis through the Notch1 signaling pathway.Molecular genetics and genomics : MGG · 2026Article
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- Regionalized regulation of actomyosin organization influences cardiomyocyte cell shape changes during chamber curvature formation.Nature communications · 2026Article
- Zebrafish arterial valve development occurs through direct differentiation of second heart field progenitors.Cardiovascular research · 2025Article
- Rescue of mitochondrial dysfunction through alteration of extracellular matrix composition in barth syndrome cardiac fibroblasts.Biomaterials · 2025Article
- Development of the semicircular canals and otolithic organs of the vertebrate inner ear.Current topics in developmental biology · 2025Review
- morphoHeart: A quantitative tool for integrated 3D morphometric analyses of heart and ECM during embryonic development.PLoS biology · 2025Article
- Llgl1 mediates timely epicardial emergence and establishment of an apical laminin sheath around the trabeculating cardiac ventricle.Development (Cambridge, England) · 2024Article
- Mechanical forces remodel the cardiac extracellular matrix during zebrafish development.Development (Cambridge, England) · 2024Article
- Review
- Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping.Journal of pharmaceutical analysis · 2024Article
- Functional analysis of germline VANGL2 variants using rescue assays of vangl2 knockout zebrafish.Human molecular genetics · 2024Article
- Multiplexed spatial transcriptomics methods and the application of expansion microscopy.Frontiers in cell and developmental biology · 2024Review
- leptin b and its regeneration enhancer illustrate the regenerative features of zebrafish hearts.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Article
- Matrix produced by diseased cardiac fibroblasts affects early myotube formation and function.Acta biomaterialia · 2022Article
- Article
- Sequential action of JNK genes establishes the embryonic left-right axis.Development (Cambridge, England) · 2022Article
- Clinical and translational values of spatial transcriptomics.Signal transduction and targeted therapy · 2022Review
- Zebrafish as a Model to Study Vascular Elastic Fibers and Associated Pathologies.International journal of molecular sciences · 2022Review
- Presence of chondroitin sulphate and requirement for heparan sulphate biosynthesis in the developing zebrafish inner ear.Frontiers in cell and developmental biology · 2022Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsVertebrate heart development requires the complex morphogenesis of a linear tube to form the mature organ, a process essential for correct cardiac form and function, requiring coordination of embryonic laterality, cardiac growth, and regionalized cellular changes. While previous studies have demonstrated broad requirements for extracellular matrix (ECM) components in cardiac morphogenesis, we hypothesized that ECM regionalization may fine tune cardiac shape during heart development. METHODS AND
resultsUsing live in vivo light sheet imaging of zebrafish embryos, we describe a left-sided expansion of the ECM between the myocardium and endocardium prior to the onset of heart looping and chamber ballooning. Analysis using an ECM sensor revealed the cardiac ECM is further regionalized along the atrioventricular axis. Spatial transcriptomic analysis of gene expression in the heart tube identified candidate genes that may drive ECM expansion. This approach identified regionalized expression of hapln1a, encoding an ECM cross-linking protein. Validation of transcriptomic data by in situ hybridization confirmed regionalized hapln1a expression in the heart, with highest levels of expression in the future atrium and on the left side of the tube, overlapping with the observed ECM expansion. Analysis of CRISPR-Cas9-generated hapln1a mutants revealed a reduction in atrial size and reduced chamber ballooning. Loss-of-function analysis demonstrated that ECM expansion is dependent upon Hapln1a, together supporting a role for Hapln1a in regionalized ECM modulation and cardiac morphogenesis. Analysis of hapln1a expression in zebrafish mutants with randomized or absent embryonic left-right asymmetry revealed that laterality cues position hapln1a-expressing cells asymmetrically in the left side of the heart tube.
conclusionWe identify a regionalized ECM expansion in the heart tube which promotes correct heart development, and propose a novel model whereby embryonic laterality cues orient the axis of ECM asymmetry in the heart, suggesting these two pathways interact to promote robust cardiac morphogenesis.
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