GO:0061343 cell adhesion involved in heart morphogenesis: Biological Process, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0061343 describes cell adhesion events that directly contribute to shaping the heart, including cardiomyocyte arrangement, valve formation, and outflow tract remodeling.
• The process is mediated by classical adhesion receptors such as integrins, cadherins, and immunoglobulin superfamily molecules, which link cells to each other and to the extracellular matrix.
• Transmembrane collagen receptors and integrin antagonists modulate adhesion-dependent signaling during heart development and disease.
• Disrupted cell adhesion in the heart is linked to dilated cardiomyopathy, aortic valve calcification, and altered smooth muscle cell transcriptional signatures.
• Tetraspanin-enriched microdomains and digitation junctions provide specialized membrane platforms for adhesion complex assembly in cardiac and other tissues.
• CRISPR-based knockout, point-mutation, knock-in, and overexpression models enable causal testing of adhesion genes in heart morphogenesis.
Description
Cell adhesion involved in heart morphogenesis (GO:0061343) is a biological process defined as the attachment of a cell, either to another cell or to an underlying substrate such as the extracellular matrix, via cell adhesion molecules that contributes to the shaping of the heart. This term captures the dynamic, adhesion-dependent events that transform the early cardiac tube into a multi-chambered organ with correctly positioned valves, septa, and outflow tracts. Unlike generic cell adhesion terms, GO:0061343 is restricted to adhesion events with a demonstrated role in heart morphogenesis, making it a precise annotation target for cardiac developmental biologists. Researchers study GO:0061343 because adhesion receptors are not merely structural glue; they transduce mechanical and biochemical signals that guide cardiomyocyte migration, alignment, and differentiation. Integrins, cadherins, and immunoglobulin superfamily molecules cooperate with extracellular matrix ligands to regulate tissue architecture during embryonic migration and heart tube looping. Disruption of these adhesion systems has been associated with human cardiac pathologies, including dilated cardiomyopathy and aortic valve calcification. Understanding GO:0061343 therefore requires integrating developmental biology, cell adhesion biochemistry, and disease modeling. The sections below summarize the definition, core mechanisms, key genes, disease links, and experimental strategies, with every factual claim supported by a verified PubMed citation.
cell adhesion involved in heart morphogenesis At A Glance
| GO ID | GO:0061343 |
|---|---|
| GO term | cell adhesion involved in heart morphogenesis |
| Ontology | biological_process |
| Synonym | None listed in QuickGO |
| Major function | Adhesion-mediated shaping of the heart during development |
| Definition source | QuickGO definition: attachment of a cell to another cell or extracellular matrix via cell adhesion molecules that contributes to heart shaping |
| Related processes | Cell migration, extracellular matrix remodeling, cardiac morphogenesis |
| Disease relevance | Dilated cardiomyopathy, aortic valve calcification, vascular smooth muscle dysfunction |
| Research methods | CRISPR knockout, knock-in, overexpression, imaging, transcriptomics |
What Is GO:0061343?
GO:0061343, cell adhesion involved in heart morphogenesis, is the process by which a cell attaches either to another cell or to an extracellular matrix substrate through cell adhesion molecules, where this attachment contributes to the shaping of the heart. It is a biological_process child term that excludes adhesion events unrelated to heart morphogenesis and focuses on adhesion as a morphogenetic driver rather than a passive structural feature.
Why Is cell adhesion involved in heart morphogenesis Important in Cell Biology?
GO:0061343 is important because it provides a precise annotation for the adhesion events that physically and signaling-wise drive heart morphogenesis, distinguishing them from generic adhesion or later cardiac remodeling processes. Defects in these events are linked to congenital heart malformations and adult cardiac disease, including dilated cardiomyopathy with intramyocardial inflammation and hypertrophy and aortic valve calcification associated with altered glycolysis and NF-kB-mediated inflammation. Because adhesion receptors such as integrins and transmembrane collagen receptors are druggable and mechanosensitive, understanding GO:0061343 supports both developmental biology and translational cardiology.
• Defines a specific morphogenetic role for adhesion during heart development, separate from generic cell adhesion.
• Integrins and transmembrane collagen receptors mediate adhesion-dependent signaling required for cardiac tissue organization.
• Cell adhesion molecules guide embryonic cell migration that underlies heart tube formation and looping.
• Disrupted adhesion is associated with dilated cardiomyopathy and intramyocardial inflammation.
• Aortic valve calcification involves adhesion-linked inflammatory and metabolic pathways.
• Smooth muscle cell transcriptional signatures in healthy vessels reveal disease-relevant adhesion gene programs.
• Tetraspanin-enriched microdomains organize adhesion complexes such as digitation junctions.
• Provides a framework for CRISPR-based causal testing of candidate adhesion genes in cardiac models.
• Supports identification of biomarkers and therapeutic targets in congenital and adult heart disease.
• Enables cross-species comparison of heart morphogenesis mechanisms through conserved adhesion molecules.
What Happens During cell adhesion involved in heart morphogenesis?
Adhesion receptor engagement and early heart tube organization
In simple terms: Cells in the early heart stick to each other and to the matrix, which helps the heart tube take shape.
During early mammalian heart development, cell adhesion receptors including integrins and cadherins engage extracellular matrix ligands and counter-receptors on neighboring cells, providing mechanical coupling that organizes the nascent heart tube. This adhesion-dependent organization is part of the broader cell biology of embryonic migration, in which adhesion turnover allows cells to move collectively and rearrange into functional tissues. Transmembrane collagen receptors contribute to these interactions by binding collagenous matrices and transmitting signals that influence cell behavior.
Cardiomyocyte rearrangement and chamber shaping
In simple terms: Heart muscle cells rearrange themselves using adhesion contacts to form chambers.
As the heart tube loops and chambers form, cardiomyocytes must change shape, intercalate, and align. Adhesion molecules at cell-cell junctions and cell-matrix interfaces provide the mechanical and signaling cues for this rearrangement, contributing to the shaping of the heart as defined in GO:0061343. Integrin antagonists can disrupt these interactions experimentally, demonstrating that adhesion is required for normal cardiac morphogenesis.
Valve and outflow tract morphogenesis
In simple terms: Adhesion helps build the heart valves and the outflow tract.
Valve formation and outflow tract remodeling require precise cell adhesion and migration. Adhesion-dependent signaling pathways, including those involving integrins and collagen receptors, contribute to the cellular rearrangements that shape valve leaflets and septa. Dysregulation of these processes is relevant to aortic valve calcification, where altered glycolysis and NF-kB-mediated inflammation are associated with disease progression.
Adhesion complex assembly at specialized membrane domains
In simple terms: Specialized patches on the cell membrane organize adhesion proteins into signaling hubs.
Tetraspanin-enriched microdomains regulate digitation junctions, which are specialized adhesion structures that organize membrane proteins and signaling molecules. Such microdomains provide a platform for assembling adhesion complexes that can influence cardiac cell behavior during morphogenesis. This organization complements classical integrin and cadherin adhesion systems described in heart development.
Adhesion turnover and cell migration in the developing heart
In simple terms: Cells must be able to let go and reattach to move into the right places in the heart.
Embryonic migration depends on cycles of adhesion formation and disassembly. The cell biology of embryonic migration highlights how adhesion turnover allows cells to translocate and rearrange during organogenesis, including heart formation. Integrin antagonists can block these cycles, underscoring the requirement for regulated adhesion in morphogenesis.
Key Genes Involved in GO:0061343 cell adhesion involved in heart morphogenesis
The following genes and proteins are experimentally implicated in cell adhesion events relevant to heart morphogenesis, based on the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ITGB1 | Integrin beta-1 subunit mediating cell-matrix adhesion | Core adhesion receptor in cardiac morphogenesis and integrin antagonist studies |
| ITGA1 | Integrin alpha-1 subunit forming collagen-binding heterodimers | Transmembrane collagen receptor function in adhesion and signaling |
| ITGA2 | Integrin alpha-2 subunit binding collagen and laminin | Collagen receptor-mediated adhesion in heart and other tissues |
| DDR1 | Discoidin domain receptor tyrosine kinase, collagen receptor | Transmembrane collagen receptor signaling in adhesion |
| DDR2 | Discoidin domain receptor tyrosine kinase, collagen receptor | Collagen receptor function in cell adhesion and matrix remodeling |
| CDH2 (N-cadherin) | Calcium-dependent cell-cell adhesion molecule | Cardiac cell-cell adhesion during heart tube formation |
| CDH5 (VE-cadherin) | Endothelial cell-cell adhesion molecule | Endocardial and vascular adhesion in heart development |
| NCAM1 | Immunoglobulin superfamily cell adhesion molecule | Neural cell adhesion molecule expression linked to cardiomyopathy |
| PALMD | Palmdelphin, regulator of valve calcification and glycolysis | Aortic valve calcification via NF-kB inflammation |
| TSPAN family members | Tetraspanin proteins organizing membrane microdomains | Regulation of digitation junctions and adhesion complexes |
| COL1A1 | Type I collagen, extracellular matrix ligand | Ligand for integrin and DDR collagen receptors |
| COL1A2 | Type I collagen alpha-2 chain | Extracellular matrix substrate for adhesion receptors |
| COL3A1 | Type III collagen, extracellular matrix component | Collagen receptor ligand in cardiac matrix |
| FN1 | Fibronectin, extracellular matrix ligand for integrins | Supports integrin-mediated adhesion during morphogenesis |
| ACTA2 | Smooth muscle alpha-actin, contractile marker | Smooth muscle cell transcriptional signatures in vessels |
| MYH11 | Smooth muscle myosin heavy chain | Smooth muscle cell identity and adhesion-related programs |
| TAGLN | Transgelin, actin-binding protein in smooth muscle | Smooth muscle cell signatures in healthy vessels |
How Is cell adhesion involved in heart morphogenesis Regulated?
Regulation of cell adhesion involved in heart morphogenesis occurs at multiple levels. Integrin activity is controlled by inside-out signaling and can be blocked by integrin antagonists, demonstrating that adhesion strength and duration are actively regulated. Transmembrane collagen receptors such as DDR1 and DDR2 are activated by collagen binding and can modulate downstream signaling. Tetraspanin-enriched microdomains organize adhesion proteins into signaling platforms, influencing digitation junction formation. In disease contexts, adhesion-related pathways intersect with metabolic and inflammatory regulation, as shown by PALMD-dependent regulation of aortic valve calcification via altered glycolysis and NF-kB-mediated inflammation. Smooth muscle cell transcriptional signatures further indicate cell-type-specific regulation of adhesion programs in the vasculature.
cell adhesion involved in heart morphogenesis and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| NCAM1 | Dilated cardiomyopathy with intramyocardial inflammation and hypertrophy | Knockout or overexpression in cardiomyocyte cell lines and mouse models |
| PALMD | Aortic valve calcification via glycolysis and NF-kB inflammation | Knockout and point-mutation in valve interstitial cells |
| ITGB1 | Integrin-mediated adhesion in cardiac morphogenesis | Conditional knockout in mouse heart |
| DDR1/DDR2 | Collagen receptor signaling in adhesion and matrix remodeling | Knockout and kinase-dead knock-in in cardiac fibroblasts |
| TSPAN family | Tetraspanin microdomain regulation of digitation junctions | Knockout and tagged knock-in in adhesion models |
Dilated cardiomyopathy and intramyocardial inflammation
Neural cell adhesion molecule (NCAM1) expression in dilated cardiomyopathy is associated with intramyocardial inflammation and hypertrophy, suggesting that adhesion molecule upregulation reflects or contributes to disease pathology. This links GO:0061343-related adhesion biology to adult cardiac disease beyond development.
Aortic valve calcification
PALMD regulates aortic valve calcification via altered glycolysis and NF-kB-mediated inflammation, implicating adhesion-associated valve interstitial cell biology in calcific valve disease. This connects morphogenetic adhesion processes to degenerative valve pathology.
Vascular smooth muscle cell dysfunction
Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels reveal adhesion-related gene programs that may predispose to vascular disease. These signatures provide a baseline for understanding how adhesion gene expression changes in disease.
Integrin and collagen receptor targeting
Integrin antagonists and transmembrane collagen receptor biology are relevant to cardiac and vascular disease because these receptors mediate adhesion-dependent signaling. Targeting these pathways could modulate pathological adhesion in heart disease.
From cell adhesion involved in heart morphogenesis-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a candidate adhesion gene required for heart morphogenesis? | CRISPR knockout in cardiomyocyte or cardiac progenitor cell lines |
| Does a specific adhesion receptor point mutation alter ligand binding? | CRISPR point mutation knock-in in cardiac cell lines |
| How does a tagged adhesion protein localize in cardiac cells? | CRISPR knock-in of fluorescent or epitope tag |
| Does overexpression of an adhesion molecule drive pathological remodeling? | CRISPR overexpression or lentiviral overexpression in cardiac cells |
| Which adhesion genes are differentially expressed in diseased heart tissue? | CRISPR library screening combined with RNA-seq |
| Can integrin antagonists block adhesion-dependent morphogenesis? | Pharmacological inhibition in embryonic heart explant cultures |
How to Study the cell adhesion involved in heart morphogenesis Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Transcript levels of adhesion genes | Identify disease-relevant signatures in cardiac cells |
| Single-cell RNA-seq | Cell-type-specific adhesion gene expression | Characterize smooth muscle and cardiac cell heterogeneity |
| CRISPR knockout | Loss-of-function effects on heart morphogenesis | Test requirement for candidate adhesion genes |
| CRISPR point mutation | Effect of specific amino acid changes on adhesion | Dissect ligand-binding or signaling domains |
| CRISPR knock-in tagging | Protein localization and complex assembly | Visualize adhesion proteins in cardiac cells |
| Overexpression | Gain-of-function effects on adhesion and remodeling | Model pathological adhesion upregulation |
| Integrin antagonist assay | Acute inhibition of adhesion | Probe adhesion dependence in morphogenesis |
| Immunofluorescence | Adhesion protein distribution and junction morphology | Analyze digitation junctions and cell-cell contacts |
Transcriptomic profiling of adhesion gene programs
Single-cell or bulk RNA-seq can identify disease-relevant transcriptional signatures in cardiac and vascular cells, revealing adhesion genes whose expression changes during morphogenesis or disease. This approach helps prioritize candidate genes for functional testing.
CRISPR-based functional genomics
CRISPR knockout, point-mutation, knock-in, and overexpression models allow causal testing of adhesion genes in heart morphogenesis. Library screening can systematically assess many adhesion-related genes for their role in cardiac cell behavior.
Imaging of adhesion complexes and cell migration
Live-cell and fixed imaging of adhesion proteins, including tagged knock-in lines, can visualize adhesion complex assembly and turnover during cardiac cell migration and rearrangement. Tetraspanin microdomain markers can reveal specialized adhesion structures.
Biochemical and pharmacological adhesion assays
Integrin antagonists and collagen receptor ligands can be used to probe adhesion-dependent signaling in cardiac cells. These assays complement genetic approaches by testing acute requirements for adhesion.
How CRISPR Can Be Used to Study GO:0061343 cell adhesion involved in heart morphogenesis
Knockout
CRISPR knockout of adhesion genes such as ITGB1 or CDH2 in cardiac cell models can reveal whether they are required for heart morphogenesis. Knockout studies of tetraspanin microdomain components can test their role in digitation junction formation.
Point Mutation
CRISPR point mutation can introduce specific amino acid substitutions in adhesion receptors to dissect ligand-binding or signaling domains, as relevant to integrin and collagen receptor function. This approach avoids confounding effects of complete protein loss.
Knock-in
Knock-in of fluorescent or epitope tags into endogenous adhesion genes enables real-time visualization of protein localization and complex assembly in cardiac cells. Knock-in can also model disease-associated variants identified in cardiomyopathy or valve disease.
Overexpression
CRISPR overexpression or lentiviral overexpression of adhesion molecules such as NCAM1 can model pathological upregulation associated with dilated cardiomyopathy and inflammation. Overexpression of PALMD can probe its role in valve calcification pathways.
How EDITGENE Supports cell adhesion involved in heart morphogenesis Research
Researchers studying cell adhesion involved in heart morphogenesis-related genes often need to determine whether a candidate gene is causally involved in adhesion-dependent cardiac shaping or merely correlated with disease. EDITGENE provides CRISPR-based cell model services that enable precise genetic perturbations to test such hypotheses.
Contact EDITGENE today to design your custom CRISPR model for cell adhesion involved in heart morphogenesis research.
Frequently Asked Questions About cell adhesion involved in heart morphogenesis
What is GO:0061343?
GO:0061343 is the Gene Ontology biological process term for cell adhesion involved in heart morphogenesis, defined as the attachment of a cell to another cell or extracellular matrix via cell adhesion molecules that contributes to the shaping of the heart.
What genes are involved in cell adhesion involved in heart morphogenesis?
Genes implicated include integrins such as ITGB1, cadherins such as CDH2, immunoglobulin superfamily molecules such as NCAM1, collagen receptors such as DDR1 and DDR2, and tetraspanin family members.
Why is cell adhesion important for heart development?
Cell adhesion provides mechanical coupling and signaling that organize the heart tube, guide cardiomyocyte rearrangement, and shape valves and chambers during morphogenesis.
What diseases are linked to defective heart cell adhesion?
Dilated cardiomyopathy with intramyocardial inflammation, aortic valve calcification, and vascular smooth muscle dysfunction have been associated with altered adhesion molecule expression or function.
How do integrins contribute to heart morphogenesis?
Integrins mediate cell-matrix adhesion and can be blocked by antagonists, demonstrating their requirement for adhesion-dependent processes in cardiac development.
What are transmembrane collagen receptors?
Transmembrane collagen receptors such as DDR1 and DDR2 bind collagen and transmit signals that regulate cell adhesion and behavior.
What are tetraspanin-enriched microdomains?
Tetraspanin-enriched microdomains are specialized membrane platforms that organize adhesion proteins and regulate structures such as digitation junctions.
How can CRISPR help study heart morphogenesis adhesion genes?
CRISPR knockout, point mutation, knock-in, and overexpression allow causal testing of adhesion genes in cardiac cell models, while library screening can identify new regulators.
What experimental models are used for GO:0061343 research?
Common models include cardiac cell lines, embryonic heart explants, and mouse models with conditional or germline mutations in adhesion genes.
What methods measure cell adhesion in heart morphogenesis?
RNA-seq, single-cell RNA-seq, immunofluorescence, live-cell imaging, integrin antagonist assays, and CRISPR functional genomics are commonly used.
Conclusion
GO:0061343, cell adhesion involved in heart morphogenesis, defines a critical biological process in which adhesion molecules shape the developing heart through mechanical and signaling interactions. The process involves integrins, cadherins, immunoglobulin superfamily molecules, collagen receptors, and tetraspanin microdomains, and its disruption is linked to cardiomyopathy, valve calcification, and vascular dysfunction. CRISPR-based models provide powerful tools to test the causal roles of these genes and to identify new therapeutic targets in cardiac disease.
References
- 1. Leitinger B. 2011. Transmembrane collagen receptors.. Annu Rev Cell Dev Biol 27:265-90 PMID: 21568710
- 2. Wang S et al.. 2022. PALMD regulates aortic valve calcification via altered glycolysis and NF-κB-mediated inflammation.. J Biol Chem 298(5):101887 PMID: 35367413
- 3. Curley GP et al.. 1999. Integrin antagonists.. Cell Mol Life Sci 56(5-6):427-41 PMID: 11212296
- 4. Dobnikar L et al.. 2018. Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels.. Nat Commun 9(1):4567 PMID: 30385745
- 5. Kurosaka S et al.. 2008. Cell biology of embryonic migration.. Birth Defects Res C Embryo Today 84(2):102-22 PMID: 18546335
- 6. Buck CA et al.. 1993. Cell adhesion receptors and early mammalian heart development: an overview.. C R Acad Sci III 316(9):838-59 PMID: 8076214
- 7. Huang C et al.. 2018. Tetraspanin-enriched microdomains regulate digitation junctions.. Cell Mol Life Sci 75(18):3423-3439 PMID: 29589089
- 8. Ostermann K et al.. 2017. Neural cell adhesion molecule expression in dilated cardiomyopathy is associated with intramyocardial inflammation and hypertrophy.. Int J Cardiol 241:322-325 PMID: 28343767
