GO:0060980 cell migration involved in coronary vasculogenesis: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0060980 describes the directed movement of cells that contributes to the formation of endothelial cells lining the heart's blood vessels.
• This process is essential for coronary artery development; defects are linked to congenital heart disease and impaired cardiac repair.
• Key molecular players include LIM kinases, cadherins, NADPH oxidases, and endothelial progenitor cells.
• Monocytes and endothelial progenitor cells are recruited to the developing coronary vasculature and contribute to vessel formation.
• Reactive oxygen species (ROS) and NADPH oxidase signaling regulate the migratory behavior of endothelial progenitors.
• CRISPR-based knockout, knock-in, and overexpression models enable causal testing of candidate genes in coronary vasculogenesis.
Description
Coronary vasculogenesis is the developmental process by which the heart establishes its own blood supply. GO:0060980, cell migration involved in coronary vasculogenesis, captures the directed movement of cells that will differentiate into endothelial cells forming the heart's blood vessels. This ontology term is critical for understanding how progenitor cells navigate to the developing heart and assemble into functional coronary vessels. Disruption of this migration process is associated with congenital coronary anomalies and impaired cardiac repair after injury. Researchers studying cardiovascular development, regenerative medicine, and angiogenesis rely on this term to annotate gene functions and interpret transcriptomic or imaging data. The process involves coordinated signaling through LIM kinases, cadherins, NADPH oxidase, and chemokine gradients that guide endothelial progenitors to the coronary plexus.
cell migration involved in coronary vasculogenesis At A Glance
| GO ID | GO:0060980 |
|---|---|
| GO term | cell migration involved in coronary vasculogenesis |
| Ontology | biological_process |
| Synonym | None |
| Major function | Directed movement of progenitor cells that differentiate into coronary endothelial cells |
| Related processes | Angiogenesis, vasculogenesis, endothelial cell differentiation, cell motility |
| Key regulators | LIM kinases, cadherins, NADPH oxidase, chemokines |
| Disease relevance | Congenital heart defects, coronary artery disease, impaired cardiac repair |
What Is GO:0060980?
GO:0060980 is defined as the orderly movement of a cell from one site to another that will contribute to the differentiation of an endothelial cell that will form the blood vessels of the heart. In other words, it is the directed migration step that precedes and enables the formation of coronary endothelial cells, ensuring that progenitor cells reach the correct anatomical location to build the coronary vasculature.
Why Is cell migration involved in coronary vasculogenesis Important in Cell Biology?
Understanding GO:0060980 is essential because coronary vasculogenesis is a prerequisite for normal heart development and function. Defects in the migration of endothelial progenitors can lead to congenital coronary anomalies, myocardial ischemia, and poor recovery after cardiac injury. Moreover, the molecular mechanisms governing this migration, such as LIM kinase-mediated actin dynamics and cadherin-based adhesion, are shared with pathological angiogenesis in cancer and atherosclerosis. Therefore, studying this process provides insights into both developmental biology and disease pathogenesis, and it offers potential targets for therapeutic revascularization.
• Required for establishing the coronary circulation during embryogenesis.
• Dysregulation leads to congenital heart defects and coronary artery anomalies.
• Shares molecular machinery with tumor angiogenesis and atherosclerosis.
• Involves endothelial progenitor cells that can be harnessed for regenerative therapies.
• ROS and NADPH oxidase signaling modulate migratory capacity of endothelial cells.
• LIM kinases regulate actin cytoskeleton dynamics necessary for cell motility.
• Cadherins mediate cell-cell adhesion critical for coordinated migration.
• Monocytes contribute to angiogenesis by releasing pro-migratory factors.
• Peptide Lv promotes pathological angiogenesis, highlighting migratory pathways.
• Tissular insemination of progenitor endothelial cells is a proposed therapeutic strategy.
What Happens During cell migration involved in coronary vasculogenesis?
Initiation and Chemoattraction
In simple terms: Cells receive signals that tell them where to go.
The process begins when progenitor cells respond to chemotactic cues that guide them toward the developing heart. Monocytes and endothelial progenitor cells are recruited by factors such as vascular endothelial growth factor and stromal cell-derived factor-1, which activate migratory signaling pathways. NADPH oxidase-derived reactive oxygen species (ROS) also act as chemoattractant signals, promoting directional migration.
Cytoskeletal Rearrangement and Motility
In simple terms: The cell's internal skeleton changes shape to allow movement.
Upon stimulation, LIM kinases phosphorylate cofilin, leading to actin filament stabilization and reorganization that drives cell protrusion and forward movement. Cadherins mediate dynamic cell-cell adhesions that coordinate collective migration and maintain tissue integrity during coronary vessel formation.
Adhesion and Matrix Remodeling
In simple terms: Cells stick to and reshape their surroundings to move through tissue.
Migrating cells interact with the extracellular matrix via integrins and secrete proteases to remodel the matrix, creating paths for migration. Cadherin-mediated junctions are continuously formed and broken to allow movement while keeping cells connected. This remodeling is essential for the progenitor cells to reach the coronary plexus.
Differentiation into Coronary Endothelial Cells
In simple terms: Once they arrive, the cells become blood vessel lining cells.
After reaching the target site, the migrated cells differentiate into endothelial cells that assemble into primitive coronary vessels. This step involves the expression of endothelial markers such as CD31 and VE-cadherin, and is influenced by the local microenvironment. The entire process ensures the heart receives its own blood supply.
Key Genes Involved in GO:0060980 cell migration involved in coronary vasculogenesis
The following genes and proteins have been experimentally implicated in cell migration involved in coronary vasculogenesis or closely related angiogenic processes.
| Gene | Major Role | Research Relevance |
|---|---|---|
| LIMK1 | Phosphorylates cofilin to regulate actin dynamics | Knockout reduces cell motility; target for cardiovascular disease |
| LIMK2 | Regulates actin cytoskeleton and cell migration | Implicated in vascular remodeling and angiogenesis |
| CDH5 (VE-cadherin) | Endothelial cell-cell adhesion | Essential for vascular integrity and migration |
| CDH2 (N-cadherin) | Cell adhesion and migration | Modulates vascular smooth muscle and endothelial behavior |
| NOX1 | NADPH oxidase subunit; produces ROS | ROS-dependent migration and angiogenesis |
| NOX2 (CYBB) | NADPH oxidase subunit; ROS production | Regulates endothelial progenitor cell function |
| NOX4 | NADPH oxidase; hydrogen peroxide generation | Modulates angiogenic signaling |
| VEGFA | Chemoattractant and pro-angiogenic factor | Drives endothelial progenitor migration |
| CXCL12 (SDF-1) | Chemokine guiding progenitor cells | Recruits endothelial progenitors to ischemic tissue |
| CXCR4 | Receptor for CXCL12 | Mediates homing and migration of progenitors |
| PECAM1 (CD31) | Endothelial cell adhesion molecule | Marker of endothelial differentiation |
| KDR (VEGFR2) | VEGF receptor; promotes migration | Key mediator of angiogenic sprouting |
| MMP2 | Matrix metalloproteinase; degrades ECM | Facilitates cell migration through matrix |
| MMP9 | Matrix metalloproteinase; ECM remodeling | Involved in progenitor cell mobilization |
| ITGB1 (Integrin beta1) | ECM adhesion and signaling | Required for migration on matrix proteins |
| RAC1 | Rho GTPase; regulates actin dynamics | Controls cell protrusion and migration |
| RHOA | Rho GTPase; regulates contractility | Modulates cell migration and adhesion |
| CFL1 (Cofilin) | Actin depolymerizing factor | Target of LIMK; regulates motility |
How Is cell migration involved in coronary vasculogenesis Regulated?
The migration of cells involved in coronary vasculogenesis is tightly regulated by signaling pathways including LIM kinase/cofilin, Rho GTPases, and NADPH oxidase-derived ROS. LIM kinases are activated downstream of Rho-associated kinase (ROCK) and phosphorylate cofilin, thereby stabilizing actin filaments and promoting directional migration. Cadherin-mediated adhesion complexes dynamically regulate cell-cell contacts and cytoskeletal organization, and their expression is modulated by growth factors such as VEGF. ROS produced by NADPH oxidases act as second messengers to activate migratory signaling and are balanced by antioxidant systems. Additionally, chemokine gradients of CXCL12 and VEGF guide progenitor cells to the coronary region, and their receptors are subject to feedback regulation.
cell migration involved in coronary vasculogenesis and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| LIMK1 | Congenital heart defects; impaired cell migration | Knockout mouse; point mutation of kinase domain |
| CDH5 | Vascular permeability; coronary anomalies | Endothelial-specific knockout; knock-in of mutant cadherin |
| NOX2 | Atherosclerosis; ROS-mediated endothelial dysfunction | NOX2 knockout; overexpression of dominant-negative |
| CXCR4 | Defective progenitor homing; impaired cardiac repair | Knock-in of CXCR4 variants; knockout in endothelial lineage |
| VEGFA | Angiogenesis; coronary vessel development | Inducible overexpression; conditional knockout |
Congenital Heart Defects and Coronary Anomalies
Disruption of cell migration involved in coronary vasculogenesis can lead to congenital coronary artery anomalies, including anomalous origin of coronary arteries and coronary fistulas. Studies in animal models show that loss of LIMK1 or cadherin function impairs coronary vessel formation and causes myocardial hypoplasia. These defects highlight the importance of precise migratory control during heart development.
Atherosclerosis and Vascular Disease
Aberrant migration of endothelial progenitor cells and monocytes contributes to atherosclerosis. Monocytes recruited to the vessel wall release pro-angiogenic factors that exacerbate plaque neovascularization, a process dependent on migratory signaling. NADPH oxidase-derived ROS further promote endothelial dysfunction and pathological angiogenesis in lower extremity artery disease.
Cancer and Pathological Angiogenesis
Tumor angiogenesis shares molecular mechanisms with coronary vasculogenesis, including LIM kinase-mediated actin remodeling and cadherin-dependent adhesion. Peptide Lv has been shown to promote pathological angiogenesis, suggesting that migratory pathways are co-opted in cancer. Targeting these pathways may provide therapeutic opportunities.
Cardiac Regeneration and Repair
After myocardial infarction, the migration of endothelial progenitor cells to the injured heart is critical for neovascularization and functional recovery. Enhancing progenitor cell migration through modulation of LIM kinases or ROS signaling is a potential therapeutic strategy. Tissular insemination of progenitor endothelial cells has been proposed as a method to improve cardiac repair.
From cell migration involved in coronary vasculogenesis-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate migration of coronary endothelial progenitors? | Knockout of gene X in endothelial lineage using Cre-lox |
| Does a specific point mutation in gene X alter migratory capacity? | Point mutation knock-in via CRISPR-Cas9 |
| Does overexpression of gene X enhance coronary vasculogenesis? | Transgenic overexpression or viral delivery |
| Where and when is gene X expressed during coronary development? | Tagged knock-in (e.g., GFP) for live imaging |
| What is the transcriptional response during migration? | RNA-seq of sorted progenitor cells |
| Can gene X rescue migration defects in vitro? | Overexpression in primary endothelial cells |
How to Study the cell migration involved in coronary vasculogenesis Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live imaging | Cell movement dynamics in real time | Visualizing coronary progenitor migration in embryos |
| RNA-seq | Transcriptional changes during migration | Identifying genes upregulated in migratory cells |
| Proteomics | Protein expression and modifications | Detecting LIMK-dependent cofilin phosphorylation |
| Boyden chamber assay | Chemotactic migration capacity | Testing gene knockout effects on cell motility |
| Scratch wound assay | Directional migration and wound closure | Assessing overexpression or knockdown |
| CRISPR screen | Genome-wide identification of regulators | Discovering novel genes in coronary vasculogenesis |
| Immunofluorescence | Protein localization and cytoskeletal changes | Visualizing actin reorganization during migration |
Live Imaging and Lineage Tracing
Live imaging of fluorescently labeled endothelial progenitors in zebrafish or mouse embryos allows direct visualization of cell migration during coronary vasculogenesis. Lineage tracing using Cre-lox systems can identify the origin and fate of migrating cells.
Transcriptomic and Proteomic Profiling
RNA-seq and single-cell RNA-seq of sorted progenitor cells reveal gene expression changes during migration. Proteomics can identify post-translational modifications such as LIMK-mediated cofilin phosphorylation.
In Vitro Migration Assays
Boyden chamber and scratch wound assays measure the migratory capacity of endothelial cells or progenitors under genetic manipulation. These assays are used to test the effect of knockout or overexpression of candidate genes.
CRISPR Screening
Genome-wide CRISPR knockout or activation screens in endothelial progenitor cells can identify novel regulators of migration. Hits are validated in vivo using mouse models of coronary vasculogenesis.
How CRISPR Can Be Used to Study GO:0060980 cell migration involved in coronary vasculogenesis
Knockout
CRISPR-Cas9 knockout of candidate genes such as LIMK1 or CDH5 in endothelial progenitor cells or mouse models can determine whether they are required for cell migration involved in coronary vasculogenesis. Knockout models often show reduced migration and defective coronary vessel formation.
Point Mutation
Introducing specific point mutations (e.g., kinase-dead LIMK1) via CRISPR base editing or homology-directed repair allows precise testing of domain functions in migration. This approach distinguishes catalytic activity from scaffolding roles.
Knock-in
Knock-in of fluorescent tags (e.g., GFP) or epitope tags into endogenous loci enables live tracking of migrating cells and biochemical analysis of protein complexes. Knock-in of disease-associated variants can model human coronary anomalies.
Overexpression
CRISPR activation (CRISPRa) or transgenic overexpression of pro-migratory genes such as VEGFA or CXCL12 can enhance coronary vasculogenesis and improve cardiac repair after injury. Overexpression models are useful for gain-of-function studies.
How EDITGENE Supports cell migration involved in coronary vasculogenesis Research
Researchers studying cell migration involved in coronary vasculogenesis-related genes often need to determine whether a candidate gene is causally involved in progenitor cell recruitment, differentiation, or vessel assembly. EDITGENE provides comprehensive CRISPR-based services to generate precisely engineered cell models and animal models, enabling rigorous functional validation of genes implicated in this process.
Contact EDITGENE today to design your custom CRISPR model for cell migration involved in coronary vasculogenesis research.
Frequently Asked Questions About cell migration involved in coronary vasculogenesis
What is GO:0060980?
GO:0060980 is the Gene Ontology term for cell migration involved in coronary vasculogenesis, defined as the orderly movement of a cell that contributes to the differentiation of an endothelial cell forming the heart's blood vessels.
What genes are involved in cell migration involved in coronary vasculogenesis?
Key genes include LIMK1, LIMK2, CDH5, CDH2, NOX1, NOX2, NOX4, VEGFA, CXCL12, CXCR4, and PECAM1, among others.
How is cell migration involved in coronary vasculogenesis regulated?
It is regulated by LIM kinase/cofilin signaling, Rho GTPases, cadherin-mediated adhesion, and NADPH oxidase-derived ROS, as well as chemokine gradients.
What diseases are associated with defects in coronary vasculogenesis?
Defects are linked to congenital heart defects, coronary artery anomalies, atherosclerosis, and impaired cardiac repair after myocardial infarction.
What research methods are used to study this process?
Methods include live imaging, lineage tracing, RNA-seq, proteomics, in vitro migration assays, and CRISPR screens.
Can CRISPR be used to study cell migration involved in coronary vasculogenesis?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models enable causal testing of candidate genes in endothelial progenitor cells and animal models.
What is the role of LIM kinases in coronary vasculogenesis?
LIM kinases regulate actin cytoskeleton dynamics by phosphorylating cofilin, which is essential for cell motility during coronary vessel formation.
How do cadherins contribute to coronary vasculogenesis?
Cadherins mediate cell-cell adhesion and coordinate collective migration of endothelial progenitors, maintaining tissue integrity during vessel formation.
What is the role of NADPH oxidase in this process?
NADPH oxidase produces reactive oxygen species that act as signaling molecules to promote endothelial cell migration and angiogenesis.
How can endothelial progenitor cells be used therapeutically?
Endothelial progenitor cells can be recruited to sites of injury to promote neovascularization; enhancing their migration is a therapeutic goal.
Conclusion
GO:0060980, cell migration involved in coronary vasculogenesis, is a fundamental biological process that ensures the heart develops its own blood supply. Its molecular regulation by LIM kinases, cadherins, and ROS signaling is critical for normal development and is implicated in congenital heart defects, atherosclerosis, and cancer. Continued research using CRISPR-based models will uncover new therapeutic targets for cardiovascular disease.
References
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- 3. Jaipersad AS et al.. 2014. The role of monocytes in angiogenesis and atherosclerosis.. J Am Coll Cardiol 63(1):1-11 PMID: 24140662
- 4. Shi L et al.. 2019. Newly Identified Peptide, Peptide Lv, Promotes Pathological Angiogenesis.. J Am Heart Assoc 8(22):e013673 PMID: 31698979
- 5. Ushio-Fukai M et al.. 2009. Novel role of NADPH oxidase in angiogenesis and stem/progenitor cell function.. Antioxid Redox Signal 11(10):2517-33 PMID: 19309262
- 6. Khoo CP et al.. 2008. Endothelial progenitor cells and their potential therapeutic applications.. Regen Med 3(6):863-76 PMID: 18947309
- 7. Hutchings G et al.. 2021. Molecular Mechanisms Associated with ROS-Dependent Angiogenesis in Lower Extremity Artery Disease.. Antioxidants (Basel) 10(5) PMID: 34066926
- 8. Moldovan NI. 2003. Tissular insemination of progenitor endothelial cells: the problem, and a suggested solution.. Adv Exp Med Biol 522:99-113 PMID: 12674214
