GO:1904848 negative regulation of cell chemotaxis to fibroblast growth factor: Signaling Brake, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1904848 describes any process that stops, prevents, or reduces the directed migration of cells toward fibroblast growth factor (FGF).
• This term is a biological_process child of negative regulation of chemotaxis and is distinct from positive regulation of FGF chemotaxis.
• Key molecular players include FGF receptors (FGFR1-4), Src, Fes, Ras, Ral, and focal adhesion components that modulate chemotactic signaling.
• Inhibition of FGF-driven chemotaxis has been demonstrated for endothelial cells treated with gefitinib, linking the process to angiogenesis and cancer.
• The process is relevant to developmental morphogenesis, wound healing, and tumor microenvironment remodeling, where FGF gradients guide cell movement.
• Experimental dissection requires quantitative chemotaxis assays combined with CRISPR knockout, point mutation, or overexpression models.
Description
Cell chemotaxis to fibroblast growth factor (FGF) is a fundamental biological process that directs the movement of various cell types along FGF gradients during development, tissue repair, and disease. The Gene Ontology term GO:1904848, negative regulation of cell chemotaxis to fibroblast growth factor, captures the regulatory mechanisms that attenuate or block this directed migration. Understanding this process is critical because dysregulated FGF chemotaxis contributes to pathological angiogenesis, tumor invasion, and developmental anomalies. Researchers studying this term aim to identify the molecular brakes that normally constrain FGF-driven cell movement and to determine how their loss or gain contributes to disease. The QuickGO definition states: Any process that stops, prevents or reduces the frequency, rate or extent of cell chemotaxis to fibroblast growth factor. This definition places the term within the broader ontology of negative regulation of chemotaxis and highlights its role as a counterbalance to pro-migratory FGF signaling. The importance of GO:1904848 extends beyond basic cell biology; it is implicated in the regulation of endothelial cell behavior, skeletal myoblast migration, and dermal fibroblast responses. For example, inhibition of FGF-2-induced chemotaxis by gefitinib in endothelial cells associates with downregulation of Fes activity, directly linking a pharmacological intervention to this GO term. Similarly, Ras and Ral GTPases are required for chemotactic migration of skeletal myoblasts, and their negative regulation could represent a node of control for GO:1904848. This article synthesizes published findings to provide a research-grade overview of GO:1904848, its molecular underpinnings, and the experimental strategies used to study it.
negative regulation of cell chemotaxis to fibroblast growth factor At A Glance
| GO ID | GO:1904848 |
|---|---|
| GO term | negative regulation of cell chemotaxis to fibroblast growth factor |
| Ontology | biological_process |
| Synonym | down regulation of cell chemotaxis to fibroblast growth factor; down-regulation of cell chemotaxis to fibroblast growth factor; downregulation of cell chemotaxis to fibroblast growth factor; inhibition of cell chemotaxis to fibroblast growth factor |
| Major function | Suppresses directed cell migration toward FGF gradients |
| Related process | Negative regulation of chemotaxis (parent term) |
| Key ligands | FGF family members (e.g., FGF-2) |
| Key receptors | FGFR1-4 |
| Cellular context | Endothelial cells, skeletal myoblasts, dermal fibroblasts, and other FGF-responsive cells |
What Is GO:1904848?
GO:1904848, negative regulation of cell chemotaxis to fibroblast growth factor, is a biological process defined as any process that stops, prevents, or reduces the frequency, rate, or extent of cell chemotaxis to fibroblast growth factor. In simpler terms, it is the cellular brake that limits how strongly and how efficiently a cell moves toward an FGF signal. This term does not describe the chemotaxis itself but the regulatory events that suppress it, such as inhibition of FGF receptor signaling, modulation of downstream effectors like Src and Fes, or changes in focal adhesion dynamics. The term is a child of negative regulation of chemotaxis and is distinguished from positive regulation of cell chemotaxis to fibroblast growth factor.
Why Is negative regulation of cell chemotaxis to fibroblast growth factor Important in Cell Biology?
GO:1904848 is important because it provides a mechanistic framework for understanding how cells avoid excessive or inappropriate migration toward FGF, a process that is critical for normal development and tissue homeostasis but can become dysregulated in cancer and other diseases. The term helps researchers interpret experimental data on FGF signaling by separating pro-migratory events from the regulatory mechanisms that oppose them. In translational research, targeting negative regulators of FGF chemotaxis could offer therapeutic strategies to limit pathological angiogenesis or tumor cell dissemination.
• Provides a conceptual brake for FGF-driven cell migration, preventing uncontrolled movement during development.
• Implicated in angiogenesis, where inhibition of endothelial cell chemotaxis toward FGF-2 can suppress new blood vessel formation.
• Relevant to cancer biology because tumor cells often hijack FGF signaling for invasion and metastasis.
• Involved in skeletal muscle regeneration through regulation of myoblast chemotaxis.
• Contributes to wound healing by modulating dermal fibroblast migration.
• Serves as a counterbalance to positive regulation of FGF chemotaxis, maintaining signaling homeostasis.
• Offers potential drug targets, as shown by gefitinib-mediated inhibition of FGF-2 chemotaxis via Fes downregulation.
• Helps explain how focal adhesion disassembly and Src/Fes signaling intersect with chemotaxis.
• Guides experimental design for CRISPR screens aimed at identifying suppressors of FGF chemotaxis.
• Supports the development of cell-based models for studying chemotaxis regulation in health and disease.
What Happens During negative regulation of cell chemotaxis to fibroblast growth factor?
Initiation: FGF receptor activation and early signaling
In simple terms: FGF binds to its receptor on the cell surface, starting a signal that normally tells the cell to move.
Cell chemotaxis to fibroblast growth factor begins when FGF ligands, such as FGF-2, bind to and activate FGF receptors (FGFRs) on the cell surface. This activation triggers receptor autophosphorylation and recruitment of downstream adaptor proteins, leading to activation of Src family kinases and Ras-related GTPases. In endothelial cells, FGF-2 induces activation of Src through the tyrosine kinase Fes, which regulates focal adhesion disassembly, a prerequisite for cell movement. Negative regulation of this process can occur at the receptor level or at downstream signaling nodes.
Amplification: Ras, Ral, and focal adhesion turnover
In simple terms: The initial signal gets amplified inside the cell, and the cell starts to dismantle attachments so it can move.
Downstream of FGF receptor activation, Ras and Ral GTPases are involved in chemotactic migration of skeletal myoblasts, indicating that these small GTPases are required for the motile response. Focal adhesion formation and disassembly are dynamically regulated during endothelial cell migration and morphogenesis, and interference with these processes can block chemotaxis. Negative regulation of FGF chemotaxis may therefore involve inhibition of Ras/Ral activation or stabilization of focal adhesions to prevent productive movement.
Braking: Inhibition of FGF-2-induced chemotaxis by gefitinib and Fes downregulation
In simple terms: Certain drugs or cellular changes can put the brakes on the movement signal, stopping the cell from migrating toward FGF.
Gefitinib, an EGFR tyrosine kinase inhibitor, inhibits endothelial cell chemotaxis toward FGF-2, and this inhibition is associated with downregulation of Fes activity. This finding directly demonstrates a pharmacological intervention that reduces the frequency or extent of FGF chemotaxis, fitting the definition of GO:1904848. The mechanism involves disruption of Src activation through Fes, which impairs focal adhesion disassembly and thus cell movement.
Integration with other signaling pathways
In simple terms: Other signals in the cell can also influence whether the cell moves toward FGF or stays put.
Negative regulation of FGF chemotaxis does not occur in isolation; it can be modulated by crosstalk with other pathways. For example, Axl tyrosine kinase receptor inhibits vascular endothelial growth factor receptor 2-mediated endothelial cell activation, suggesting that similar receptor tyrosine kinase crosstalk may influence FGF-driven responses. Additionally, transforming growth factor beta 1 regulates Meox1 transcription and affects cell migration of adult human dermal fibroblasts, indicating that TGF-beta signaling can intersect with FGF chemotaxis regulation. Pdgfab/Pdgfra-mediated chemoattraction guides migration of sclerotome-derived fibroblast precursors in zebrafish, highlighting that other growth factor gradients can compete with or modulate FGF-directed movement.
Outcome: Reduced directed migration and altered cell behavior
In simple terms: When the brakes are applied, the cell moves less toward FGF, which can change how tissues form or heal.
The ultimate outcome of negative regulation of cell chemotaxis to fibroblast growth factor is a reduction in the frequency, rate, or extent of directed cell migration toward FGF. This can lead to decreased angiogenesis, impaired wound healing, or altered developmental morphogenesis depending on the cellular context. In pathological settings, loss of this negative regulation may contribute to excessive FGF-driven migration, such as in tumor angiogenesis or cancer cell invasion.
Key Genes Involved in GO:1904848 negative regulation of cell chemotaxis to fibroblast growth factor
The following genes and proteins have been experimentally linked to the regulation of cell chemotaxis to fibroblast growth factor or to the signaling pathways that mediate it.
| Gene | Major Role | Research Relevance |
|---|---|---|
| FGF2 | Ligand that stimulates chemotaxis | Used to induce chemotaxis in endothelial and other cells |
| FGFR1 | Receptor for FGF-2 | Mediates pro-migratory signaling; target for negative regulation |
| SRC | Kinase activated downstream of FGF-2 | Regulates focal adhesion disassembly; its inhibition blocks chemotaxis |
| FES | Tyrosine kinase that activates Src | Downregulation of Fes inhibits FGF-2 chemotaxis |
| RAS | Small GTPase required for chemotaxis | Involved in skeletal myoblast migration; potential brake node |
| RAL | Small GTPase required for chemotaxis | Involved in skeletal myoblast migration; potential brake node |
| PTK2 | Focal adhesion kinase | Regulates focal adhesion turnover during migration |
| PXN | Paxillin, focal adhesion protein | Component of focal adhesions; modulates migration |
| VCL | Vinculin, focal adhesion protein | Links adhesion to cytoskeleton; affects chemotaxis |
| AXL | Receptor tyrosine kinase | Inhibits VEGFR2-mediated endothelial activation; possible crosstalk |
| VEGFR2 | Receptor for VEGF | Crosstalk with FGF signaling in endothelial cells |
| MEOX1 | Transcription factor | Regulated by TGF-beta1; affects dermal fibroblast migration |
| TGFB1 | Growth factor | Modulates Meox1 and cell migration |
| PDGFRA | Receptor for PDGF | Guides fibroblast precursor migration; may compete with FGF |
| PDGFAB | Ligand for PDGFRA | Chemoattractant for sclerotome-derived fibroblasts |
| CXCL4L1 | Chemokine | Isoforms characterized in platelets; potential modulator of chemotaxis |
| GEFITINIB | EGFR inhibitor | Inhibits FGF-2 chemotaxis via Fes downregulation |
How Is negative regulation of cell chemotaxis to fibroblast growth factor Regulated?
The process of negative regulation of cell chemotaxis to fibroblast growth factor is itself regulated at multiple levels. Pharmacological inhibition of EGFR by gefitinib leads to downregulation of Fes activity and consequent inhibition of FGF-2-induced endothelial cell chemotaxis. This suggests that upstream receptor tyrosine kinases can modulate the negative regulation of FGF chemotaxis. Additionally, crosstalk with other signaling pathways, such as Axl-mediated inhibition of VEGFR2 and TGF-beta1 regulation of Meox1, may influence the balance between pro- and anti-migratory signals. The presence of competing chemoattractants, such as PDGF-AB, can also redirect cell migration away from FGF gradients. At the molecular level, the stability of focal adhesions and the activity of Src and Fes are key determinants of whether chemotaxis proceeds or is suppressed.
negative regulation of cell chemotaxis to fibroblast growth factor and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| FGF2 | Tumor angiogenesis | Endothelial cell chemotaxis assay with FGF-2 gradient |
| FES | Cancer, angiogenesis | Fes knockout or knockdown in endothelial cells |
| RAS | Muscle regeneration, cancer | Ras mutant myoblasts in chemotaxis assays |
| MEOX1 | Fibrosis, wound healing | TGF-beta1-treated dermal fibroblasts with Meox1 knockdown |
| PDGFRA | Developmental migration defects | Zebrafish pdgfra mutants |
Cancer and tumor angiogenesis
FGF-driven chemotaxis contributes to tumor angiogenesis and cancer cell invasion, and negative regulation of this process is critical to limit pathological blood vessel formation. Gefitinib-mediated inhibition of endothelial cell chemotaxis toward FGF-2 demonstrates that pharmacological intervention can suppress this pro-angiogenic behavior. Loss of negative regulators may therefore promote tumor progression.
Developmental disorders
During embryogenesis, FGF gradients guide cell migration for tissue patterning, and negative regulation ensures proper morphogenesis. Disruption of PDGF or FGF chemotaxis can lead to abnormal migration of sclerotome-derived fibroblast precursors, as shown in zebrafish. Such defects may underlie congenital anomalies.
Wound healing and fibrosis
Dermal fibroblast migration is essential for wound healing, and TGF-beta1 regulates Meox1 to influence this process. Excessive or insufficient negative regulation of FGF chemotaxis could contribute to impaired healing or fibrotic disorders.
Muscle regeneration
Skeletal myoblast chemotaxis requires Ras and Ral GTPases, and negative regulation of this migration may affect muscle repair. Dysregulation could impair regeneration after injury.
From negative regulation of cell chemotaxis to fibroblast growth factor-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X negatively regulate FGF chemotaxis? | CRISPR knockout of gene X in endothelial cells followed by FGF-2 chemotaxis assay |
| Does a point mutation in FES affect its ability to inhibit chemotaxis? | CRISPR point mutation knock-in of FES variants in endothelial cells |
| Does overexpression of a candidate brake reduce FGF chemotaxis? | Lentiviral overexpression of gene X in myoblasts or fibroblasts |
| Can tagged knock-in reveal localization of a negative regulator? | CRISPR knock-in of fluorescent tag on gene X |
| Does pharmacological inhibition mimic genetic knockout? | Gefitinib treatment of endothelial cells in chemotaxis assays |
| Does crosstalk with PDGF affect FGF chemotaxis? | Zebrafish pdgfra mutants or PDGF-AB co-treatment |
How to Study the negative regulation of cell chemotaxis to fibroblast growth factor Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Boyden chamber chemotaxis | Number of cells migrating toward FGF | Testing inhibitors or gene knockouts |
| Microfluidic gradient assay | Directionality and speed of cell movement | Live-cell imaging of chemotaxis |
| CRISPR knockout screen | Genes whose loss enhances chemotaxis | Discovery of negative regulators |
| Phosphoproteomics | Changes in phosphorylation of signaling proteins | Mapping Fes/Src pathways |
| Immunofluorescence | Focal adhesion number and size | Assessing adhesion dynamics |
| Western blot | Protein expression and activation state | Validating knockdown or overexpression |
| qRT-PCR | mRNA levels of candidate genes | Confirming transcriptional changes |
| Zebrafish migration assay | In vivo cell migration patterns | Developmental studies |
Chemotaxis assays
The gold standard for studying GO:1904848 is the Boyden chamber or microfluidic chemotaxis assay, where cells migrate toward an FGF gradient. Quantification of migrated cells or tracking of cell trajectories provides a direct measure of negative regulation.
CRISPR-based genetic screens
Pooled CRISPR knockout screens can identify genes whose loss increases FGF chemotaxis, revealing candidate negative regulators. Such screens require robust chemotaxis readouts and next-generation sequencing to quantify sgRNA enrichment.
Phosphoproteomics and signaling analysis
Mass spectrometry-based phosphoproteomics can map changes in Src, Fes, and focal adhesion proteins upon FGF stimulation and negative regulation. This approach identifies phosphorylation events that correlate with inhibited chemotaxis.
Live-cell imaging of focal adhesions
Fluorescent tagging of focal adhesion proteins like paxillin or vinculin allows real-time visualization of adhesion dynamics during FGF chemotaxis. Negative regulators may stabilize adhesions or prevent their disassembly.
How CRISPR Can Be Used to Study GO:1904848 negative regulation of cell chemotaxis to fibroblast growth factor
Knockout
CRISPR knockout of candidate negative regulators, such as FES or RAS, can be used to test whether their loss enhances FGF-2-induced chemotaxis. Endothelial cells with FES knockout are expected to show increased migration toward FGF-2 if Fes normally acts as a brake.
Point Mutation
Point mutations in kinase domains of FES or SRC can be introduced via CRISPR to dissect which catalytic activities are required for negative regulation of FGF chemotaxis. Such models help distinguish scaffolding functions from kinase activity.
Knock-in
Knock-in of fluorescent tags (e.g., GFP) on endogenous FES or focal adhesion proteins allows real-time tracking of their localization during chemotaxis. This can reveal whether negative regulators are recruited to nascent adhesions to halt migration.
Overexpression
CRISPR activation or lentiviral overexpression of candidate genes can test sufficiency for inhibiting FGF chemotaxis. Overexpression of a negative regulator should reduce the frequency or extent of directed migration.
How EDITGENE Supports negative regulation of cell chemotaxis to fibroblast growth factor Research
Researchers studying negative regulation of cell chemotaxis to fibroblast growth factor-related genes often need to determine whether a candidate gene is causally involved in suppressing FGF-driven migration. This requires precise genetic manipulation, quantitative chemotaxis assays, and robust bioinformatics to interpret signaling networks.
Contact EDITGENE today to design your custom CRISPR model for negative regulation of cell chemotaxis to fibroblast growth factor research.
Frequently Asked Questions About negative regulation of cell chemotaxis to fibroblast growth factor
What is GO:1904848?
GO:1904848 is the Gene Ontology term for negative regulation of cell chemotaxis to fibroblast growth factor, defined as any process that stops, prevents, or reduces the frequency, rate, or extent of cell chemotaxis to fibroblast growth factor.
What genes are involved in negative regulation of cell chemotaxis to fibroblast growth factor?
Key genes include FGF2, FGFR1, SRC, FES, RAS, RAL, and focal adhesion components such as PTK2, PXN, and VCL.
How is negative regulation of FGF chemotaxis studied?
Common methods include Boyden chamber chemotaxis assays, CRISPR knockout screens, phosphoproteomics, and live-cell imaging of focal adhesions.
What diseases are associated with dysregulated FGF chemotaxis?
Dysregulation is linked to cancer angiogenesis, developmental disorders, impaired wound healing, and muscle regeneration defects.
Which drugs inhibit FGF-2-induced chemotaxis?
Gefitinib inhibits endothelial cell chemotaxis toward FGF-2 by downregulating Fes activity.
What is the role of Fes in FGF chemotaxis?
Fes activates Src downstream of FGF-2, and its downregulation inhibits focal adhesion disassembly and chemotaxis.
How do Ras and Ral contribute to FGF chemotaxis?
Ras and Ral are required for chemotactic migration of skeletal myoblasts, and their negative regulation could suppress this movement.
Can CRISPR be used to study GO:1904848?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are powerful tools to dissect the genetic basis of negative regulation of FGF chemotaxis.
What is the difference between positive and negative regulation of FGF chemotaxis?
Positive regulation promotes cell migration toward FGF, while negative regulation (GO:1904848) suppresses or reduces it.
How does TGF-beta signaling affect FGF chemotaxis?
TGF-beta1 regulates Meox1 transcription and influences dermal fibroblast migration, indicating crosstalk with FGF chemotaxis pathways.
Conclusion
GO:1904848, negative regulation of cell chemotaxis to fibroblast growth factor, represents a critical regulatory node that prevents excessive or inappropriate cell migration toward FGF gradients. Through mechanisms involving Fes, Src, Ras, Ral, and focal adhesion dynamics, cells can attenuate FGF-driven chemotaxis, with profound implications for angiogenesis, development, and tissue repair. Understanding this process requires integrated experimental approaches, including CRISPR-based genetic models and quantitative chemotaxis assays. EDITGENE provides comprehensive services to accelerate research on this important biological process.
References
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