GO:0035441 cell migration involved in vasculogenesis: Embryonic Blood Vessel Formation, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0035441 describes the directed movement of cells that contributes to the de novo formation of endothelial blood vessels and tubes.
• Vasculogenesis is distinct from angiogenesis: it refers to the initial assembly of blood vessels from mesodermal precursors, often called angioblasts or hemangioblasts.
• Key molecular drivers include VEGF signaling, which guides endothelial cell migration and survival during vascular development.
• PTEN modulates vasculogenesis in early embryos by regulating cell migration and survival.
• Mutations in genes such as MAP2K1 can alter vasculogenesis and are linked to vascular malformations.
• Studying this process helps understand cardiovascular development, vascular anomalies, and potential regenerative therapies.
Description
Cell migration involved in vasculogenesis (GO:0035441) is a biological process 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 de novo blood vessels and tubes. This process is fundamental during embryonic development, where mesodermal precursor cells migrate and assemble into primary vascular networks. Unlike angiogenesis, which involves sprouting from existing vessels, vasculogenesis represents the initial formation of blood vessels from progenitor cells. Understanding this process is critical for researchers studying cardiovascular development, vascular diseases, and tissue regeneration. The migration of endothelial precursors is tightly regulated by signaling pathways, including VEGF and its receptors, which guide cells to appropriate locations for tube formation. Disruptions in these migratory events can lead to vascular malformations, impaired organ development, and contribute to pathological conditions such as arteriovenous malformations. Therefore, investigating the molecular mechanisms of cell migration during vasculogenesis provides insights into both normal physiology and disease states.
cell migration involved in vasculogenesis At A Glance
| GO ID | GO:0035441 |
|---|---|
| GO term | cell migration involved in vasculogenesis |
| Ontology | biological_process |
| Synonym | None |
| Major function | Directed movement of cells contributing to de novo blood vessel formation |
| Related process | Vasculogenesis, endothelial cell differentiation, tube formation |
| Key regulators | VEGF signaling, PTEN, MAP2K1, LIM kinases |
| Disease relevance | Vascular malformations, cardiovascular disorders, cancer |
What Is GO:0035441?
GO:0035441, cell migration involved in vasculogenesis, refers to the directed movement of cells that ultimately contributes to the differentiation of endothelial cells forming new blood vessels and tubes from scratch. This process is essential for the initial establishment of the vascular system during embryonic development, where precursor cells migrate to specific sites and organize into primitive vascular networks.
Why Is cell migration involved in vasculogenesis Important in Cell Biology?
Cell migration involved in vasculogenesis is crucial because it underpins the formation of the primary vascular system during embryogenesis, ensuring proper oxygen and nutrient delivery to developing tissues. Defects in this process can cause embryonic lethality, vascular malformations, and contribute to diseases such as arteriovenous malformations and cancer. Understanding the molecular cues that guide endothelial precursor migration offers potential therapeutic targets for regenerative medicine and vascular pathologies.
• Essential for embryonic development and organogenesis.
• Defects lead to vascular malformations and cardiovascular diseases.
• VEGF signaling is a key regulator of endothelial cell migration during vasculogenesis.
• PTEN modulates vasculogenesis by affecting cell migration and survival.
• LIM kinases are involved in cytoskeletal dynamics required for cell migration.
• MAP2K1 mutations alter vasculogenesis and are linked to arteriovenous malformations.
• Neurotrophin Neuritin1 affects melanoma migration and vascular mimicry, highlighting parallels.
• Macrophage plasticity can influence vascular remodeling and migration.
• Studying this process aids in developing cell-based therapies for ischemic diseases.
• Provides insights into tumor angiogenesis and metastasis.
What Happens During cell migration involved in vasculogenesis?
Specification and Differentiation of Angioblasts
In simple terms: Precursor cells become specialized endothelial cells.
During early embryogenesis, mesodermal cells differentiate into angioblasts, the endothelial precursor cells. This specification is driven by signaling pathways including VEGF and is influenced by transcription factors. PTEN has been shown to modulate vasculogenesis in early chick embryos, affecting the migration and survival of these precursors. The differentiation of angioblasts is a prerequisite for their subsequent migration and assembly into vascular networks.
Directed Migration of Endothelial Precursors
In simple terms: Cells move to the right place to form blood vessels.
Angioblasts migrate from their sites of origin to form the primary vascular plexus. This migration is guided by chemoattractants such as VEGF, which binds to receptors on endothelial cells and activates signaling cascades that reorganize the cytoskeleton. LIM kinases regulate actin dynamics and are critical for cell motility during this process. Disruption of migratory cues can lead to abnormal vascular patterning, as seen in MAP2K1 mutations associated with arteriovenous malformations.
Assembly into Cord-like Structures and Tube Formation
In simple terms: Migrating cells link up to form tubes.
After migration, endothelial cells align and connect to form cord-like structures that subsequently lumenize into tubes. This step involves cell-cell adhesion molecules and interactions with the extracellular matrix. The process is essential for establishing a functional circulatory system, and its failure results in defective vasculature. VEGF signaling continues to play a role in maintaining the survival and organization of these newly formed vessels.
Remodeling and Stabilization of the Primary Vascular Network
In simple terms: The early vessels are refined and stabilized.
The initial vascular plexus undergoes remodeling, where some vessels regress and others stabilize by recruiting mural cells. This phase involves complex signaling, including factors that regulate endothelial cell survival and migration. Macrophages can influence this remodeling through their plasticity and secretion of angiogenic factors. Proper stabilization is crucial for preventing vascular leakage and malformations.
Key Genes Involved in GO:0035441 cell migration involved in vasculogenesis
The following genes and proteins are key players in cell migration involved in vasculogenesis, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| VEGFA | Primary chemoattractant for endothelial cell migration | Target for modulating vasculogenesis in development and disease |
| PTEN | Modulates vasculogenesis by affecting cell migration and survival | Studied in early chick embryos to understand vascular development |
| MAP2K1 | Kinase in MAPK pathway; mutations alter vasculogenesis | Linked to arteriovenous malformations; model for vascular anomalies |
| LIMK1 | Regulates actin cytoskeleton dynamics during cell migration | Potential target for cardiovascular diseases |
| LIMK2 | Involved in cytoskeletal reorganization and cell motility | Implicated in vascular health and disease |
| NRP1 | Co-receptor for VEGF; guides endothelial migration | Modulates vasculogenesis and angiogenesis |
| NRP2 | VEGF co-receptor; involved in vascular patterning | Studied in vascular development |
| FLT1 | VEGF receptor; regulates endothelial migration and survival | Key mediator of vasculogenesis |
| KDR | VEGF receptor; promotes endothelial proliferation and migration | Central to vasculogenesis signaling |
| CDH5 | Endothelial adherens junction protein; stabilizes tubes | Marker of endothelial differentiation |
| PECAM1 | Endothelial cell adhesion molecule; involved in migration | Used as endothelial marker |
| TIE1 | Receptor tyrosine kinase; regulates vascular remodeling | Studied in vascular stabilization |
| TIE2 | Angiopoietin receptor; controls vessel stabilization | Target for vascular normalization |
| SOX17 | Transcription factor for endothelial specification | Regulates angioblast differentiation |
| ETV2 | Master regulator of endothelial lineage | Essential for vasculogenesis |
| CPG15 | Neurotrophin involved in migration and vascular mimicry | Studied in melanoma |
| MMP2 | Matrix metalloproteinase; facilitates cell migration | Remodels extracellular matrix during vasculogenesis |
How Is cell migration involved in vasculogenesis Regulated?
Cell migration involved in vasculogenesis is regulated by a complex interplay of signaling pathways. VEGF signaling is a primary regulator, activating receptors that promote endothelial cell migration, proliferation, and survival. PTEN acts as a modulator by influencing cell migration and survival during early vasculogenesis. LIM kinases regulate actin cytoskeletal dynamics, which are essential for cell motility. Additionally, MAP2K1 mutations can alter vasculogenesis, highlighting the role of MAPK signaling in vascular development. Macrophages and their plasticity can also influence vascular remodeling through secretion of growth factors and cytokines.
cell migration involved in vasculogenesis and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| MAP2K1 | Arteriovenous malformation | Knock-in of mutant MAP2K1 in endothelial cells |
| PTEN | Vascular development defects | Knockout in chick embryos or zebrafish |
| VEGFA | Cardiovascular disorders, cancer | Overexpression or knockout in mouse models |
| LIMK1 | Cardiovascular disease | Knockout mice for LIMK1 |
| CPG15 | Melanoma vascular mimicry | Overexpression in melanoma cell lines |
Vascular Malformations
Disruptions in cell migration during vasculogenesis can lead to vascular malformations such as arteriovenous malformations (AVMs). Mutations in MAP2K1 have been shown to affect vasculogenesis and are associated with AVMs, suggesting that altered endothelial migration contributes to abnormal vessel formation. Understanding these mechanisms may provide therapeutic targets for treating vascular anomalies.
Cardiovascular Diseases
Proper vasculogenesis is essential for cardiovascular development. Defects in endothelial precursor migration can result in congenital heart defects and impaired vascular function. LIM kinases, which regulate cytoskeletal dynamics, are implicated in cardiovascular health and disease, making them potential targets for intervention. VEGF signaling, critical for vasculogenesis, is also involved in various cardiovascular pathologies.
Cancer and Tumor Angiogenesis
Tumor cells can mimic vasculogenic processes to support their growth. Neurotrophin Neuritin1 (cpg15) has been shown to be involved in melanoma migration, attachment-independent growth, and vascular mimicry, a process where tumor cells form vessel-like structures. This highlights the relevance of vasculogenesis-related migration in cancer progression and the potential for targeting these pathways in oncology.
From cell migration involved in vasculogenesis-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate endothelial migration during vasculogenesis? | Knockout of gene X in endothelial cells or zebrafish |
| Does a specific point mutation in gene Y alter vasculogenesis? | Point mutation knock-in in mouse or cell lines |
| What is the role of gene Z in vascular tube formation? | Knock-in of tagged gene Z for live imaging |
| Can overexpression of gene W enhance vasculogenesis? | Overexpression of gene W in endothelial progenitor cells |
| Is gene V required for VEGF-induced migration? | Knockout of gene V followed by VEGF stimulation |
| Does gene U affect vascular malformations? | Conditional knockout in mouse endothelium |
How to Study the cell migration involved in vasculogenesis Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live imaging | Cell migration dynamics and tube formation | Visualizing vasculogenesis in zebrafish or mouse embryos |
| RNA-seq | Transcriptional changes during vasculogenesis | Identifying genes differentially expressed in migrating endothelial cells |
| Proteomics | Protein expression and phosphorylation | Mapping signaling pathways downstream of VEGF |
| CRISPR screen | Genes required for endothelial migration | Unbiased discovery of vasculogenesis regulators |
| In vitro migration assay | Cell motility and chemotaxis | Testing candidate genes in endothelial cell lines |
| Immunofluorescence | Protein localization and cytoskeletal changes | Studying LIM kinase effects on actin |
| Tube formation assay | Ability of endothelial cells to form networks | Assessing angiogenic potential in vitro |
| Flow cytometry | Endothelial marker expression | Isolating endothelial precursors |
Live Imaging of Endothelial Cell Migration
Live imaging techniques, such as time-lapse microscopy of fluorescently labeled endothelial cells in zebrafish or mouse embryos, allow direct observation of cell migration during vasculogenesis. This method provides spatial and temporal dynamics of endothelial precursor movement and tube formation.
Transcriptomic Analysis of Vasculogenesis
RNA sequencing (RNA-seq) of endothelial cells at different stages of vasculogenesis can identify genes and pathways involved in migration. Comparative transcriptomics between wild-type and mutant embryos reveals candidate regulators. For example, studies on PTEN modulation of vasculogenesis have utilized such approaches.
Proteomic and Phosphoproteomic Profiling
Mass spectrometry-based proteomics can quantify protein expression and phosphorylation changes during endothelial migration. This helps identify signaling cascades downstream of VEGF and other regulators. LIM kinase substrates and their phosphorylation status can be assessed to understand cytoskeletal regulation.
CRISPR-Based Genetic Screens
Pooled CRISPR knockout screens in endothelial cells or zebrafish can systematically identify genes required for cell migration during vasculogenesis. Libraries targeting kinases, phosphatases, or transcription factors can uncover novel regulators. Hits can be validated by individual knockout and migration assays.
How CRISPR Can Be Used to Study GO:0035441 cell migration involved in vasculogenesis
Knockout
CRISPR knockout of candidate genes in endothelial cells or model organisms can determine their necessity for cell migration during vasculogenesis. For example, knocking out PTEN in chick embryos revealed its role in modulating vasculogenesis. Knockout of LIM kinases can impair cytoskeletal dynamics and migration.
Point Mutation
Introducing specific point mutations via CRISPR, such as those found in MAP2K1 in arteriovenous malformations, allows researchers to study how these mutations affect endothelial migration and vasculogenesis. This approach provides insights into disease mechanisms.
Knock-in
Knock-in of fluorescent tags or reporter genes into endogenous loci enables live tracking of endothelial cells during migration. Tagging genes like CDH5 or PECAM1 allows visualization of vasculogenesis in real time.
Overexpression
CRISPR activation (CRISPRa) or transgenic overexpression of pro-migratory genes such as VEGFA can enhance vasculogenesis. Overexpression studies help identify sufficiency of a gene to drive endothelial migration and tube formation.
How EDITGENE Supports cell migration involved in vasculogenesis Research
Researchers studying cell migration involved in vasculogenesis-related genes often need to determine whether a candidate gene is causally involved in endothelial migration, tube formation, or vascular patterning. EDITGENE provides comprehensive CRISPR-based services to generate precisely engineered cell and animal models, enabling functional validation of genes in this critical process.
Contact EDITGENE today to design your custom CRISPR model for cell migration involved in vasculogenesis research.
Frequently Asked Questions About cell migration involved in vasculogenesis
What is cell migration involved in vasculogenesis?
It is the directed movement of cells that contributes to the formation of new blood vessels from endothelial precursors, as defined by GO:0035441.
What genes are involved in cell migration involved in vasculogenesis?
Key genes include VEGFA, PTEN, MAP2K1, LIMK1, LIMK2, and others that regulate endothelial migration and tube formation.
How is vasculogenesis different from angiogenesis?
Vasculogenesis is the de novo formation of blood vessels from precursor cells, while angiogenesis is the formation of new vessels from existing ones.
What diseases are associated with defects in vasculogenesis?
Defects can lead to arteriovenous malformations, cardiovascular disorders, and contribute to cancer progression.
What methods are used to study cell migration during vasculogenesis?
Common methods include live imaging, RNA-seq, proteomics, CRISPR screens, and in vitro migration assays.
How does VEGF signaling regulate vasculogenesis?
VEGF binds to receptors on endothelial cells, activating pathways that promote migration, proliferation, and survival during vasculogenesis.
What is the role of PTEN in vasculogenesis?
PTEN modulates vasculogenesis by affecting cell migration and survival, as shown in early chick embryos.
Can CRISPR be used to study vasculogenesis?
Yes, CRISPR knockout, knock-in, and overexpression models enable functional studies of genes involved in endothelial migration.
What are the key steps in cell migration involved in vasculogenesis?
The process includes angioblast specification, directed migration, assembly into tubes, and remodeling of the vascular network.
Why is cell migration involved in vasculogenesis important for cancer research?
Tumor cells can mimic vasculogenic processes, and genes like CPG15 are implicated in melanoma vascular mimicry, making this process relevant to cancer.
Conclusion
Cell migration involved in vasculogenesis (GO:0035441) is a fundamental biological process that drives the formation of the primary vascular system. Its regulation by VEGF, PTEN, MAP2K1, and LIM kinases highlights the complexity of endothelial precursor migration and tube formation. Dysregulation of this process contributes to vascular malformations, cardiovascular diseases, and cancer, making it a critical area of research. Advances in CRISPR-based models and imaging technologies continue to unravel the molecular mechanisms, offering potential therapeutic targets for vascular disorders.
References
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- 3. Li Y et al.. 2013. PTEN is involved in modulation of vasculogenesis in early chick embryos.. Biol Open 2(6):587-95 PMID: 23789109
- 5. Sudduth CL et al.. 2023. Arteriovenous malformation Map2k1 mutation affects vasculogenesis.. Sci Rep 13(1):11074 PMID: 37422456
- 6. Lateef OM et al.. 2024. LIM kinases in cardiovascular health and disease.. Front Physiol 15:1506356 PMID: 39744707
- 7. Drake CJ. 2003. Embryonic and adult vasculogenesis.. Birth Defects Res C Embryo Today 69(1):73-82 PMID: 12768659
- 8. Bosserhoff AK et al.. 2017. The neurotrophin Neuritin1 (cpg15) is involved in melanoma migration, attachment independent growth, and vascular mimicry.. Oncotarget 8(1):1117-1131 PMID: 27901477
