GO:1905310 regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis: Signaling Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1905310 describes the biological process that modulates the frequency, rate or extent of cardiac neural crest cell migration specifically during outflow tract morphogenesis.
• Cardiac neural crest cells are essential for septation and remodeling of the outflow tract; their migration is controlled by endothelin, BMP, integrin-linked kinase, AP-2alpha, and histone deacetylase 3 [2,4,5,6,8].
• Disruption of this process causes conotruncal heart defects such as persistent truncus arteriosus and tetralogy of Fallot [1,5,8].
• Key signaling inputs include endothelin-Cdc42 activation, BMPRIA-mediated signaling, and integrin-linked kinase-dependent cytoskeletal dynamics [2,4,5].
• CRISPR knockout, point-mutation, knock-in, and overexpression models are powerful tools to dissect causal roles of candidate genes in this process [2,4,5,6].
• EDITGENE provides end-to-end CRISPR cell model and library screening services to study regulation of cardiac neural crest cell migration in outflow tract morphogenesis.
Description
The Gene Ontology term GO:1905310, regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis, defines any process that modulates the frequency, rate or extent of cardiac neural crest cell migration specifically during the formation of the cardiac outflow tract. Cardiac neural crest cells are a specialized population of migratory cells that originate from the dorsal neural tube and migrate into the developing heart, where they contribute to the septation and remodeling of the outflow tract. Their precise regulation is critical because defects in their migration lead to severe congenital heart defects, including persistent truncus arteriosus and tetralogy of Fallot [1,5,8]. This process is regulated by a complex interplay of signaling pathways and transcription factors. Endothelin signaling activates Cdc42 to control neural crest cell migration in the cardiac outflow tract. BMP receptor IA (BMPRIA) is required in neural crest cells for outflow tract and ventricular myocardium development. Integrin-linked kinase is necessary for neural crest migration and differentiation, and its loss impairs outflow tract morphogenesis. AP-2alpha is also essential for cardiac outflow tract morphogenesis. Additionally, histone deacetylase 3 regulates smooth muscle differentiation in neural crest cells and outflow tract development. Understanding GO:1905310 is therefore central to developmental biology and congenital heart disease research. Researchers study this process using genetic models, live imaging, and transcriptomics to identify the molecular players and their regulatory relationships [1,2,4,5,6,7,8]. The term provides a standardized framework for annotating gene functions and for comparing experimental results across studies.
regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis At A Glance
| GO ID | GO:1905310 |
|---|---|
| GO term | regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis |
| Ontology | biological_process |
| Synonym | none |
| Major function | Modulates the frequency, rate or extent of cardiac neural crest cell migration during outflow tract morphogenesis |
| Related process | cardiac neural crest cell migration involved in outflow tract morphogenesis |
| Related anatomy | cardiac outflow tract |
| Key regulators | Endothelin, Cdc42, BMPRIA, integrin-linked kinase, AP-2alpha, HDAC3 |
| Disease relevance | Conotruncal heart defects, persistent truncus arteriosus, tetralogy of Fallot |
What Is GO:1905310?
GO:1905310 is a biological process term that encompasses any molecular event that changes the frequency, rate, or extent of the migration of cardiac neural crest cells during the morphogenesis of the outflow tract of the heart. It does not describe the migration itself, but rather the regulatory inputs that control it.
Why Is regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis Important in Cell Biology?
GO:1905310 is important because cardiac neural crest cell migration is a prerequisite for normal outflow tract septation, and its dysregulation directly causes life-threatening congenital heart defects [1,5,8]. The term provides a precise annotation target for genes and pathways that modulate this migration, enabling researchers to link molecular mechanisms to developmental outcomes [2,4,6].
• Defects in cardiac neural crest cell migration cause persistent truncus arteriosus and other conotruncal anomalies [1,8].
• Endothelin signaling through Cdc42 is a key regulator of neural crest migration in the outflow tract.
• BMPRIA is required in neural crest cells for outflow tract and ventricular myocardium development.
• Integrin-linked kinase is essential for neural crest migration and differentiation and for outflow tract morphogenesis.
• AP-2alpha is required for cardiac outflow tract morphogenesis.
• Histone deacetylase 3 regulates smooth muscle differentiation in neural crest cells and outflow tract development.
• Endothelial cells regulate neural crest and second heart field morphogenesis, highlighting tissue interactions.
• Numb family proteins are novel players in cardiac morphogenesis and cardiac progenitor cell differentiation.
• The term supports functional annotation of genes in developmental and congenital heart disease research.
• It enables comparative analysis of signaling pathways across species and experimental models [2,4,5,6,7,8].
What Happens During regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis?
Initiation of cardiac neural crest cell migration
In simple terms: Cardiac neural crest cells start moving from the neural tube toward the heart.
Cardiac neural crest cells delaminate from the dorsal neural tube and begin migrating toward the developing outflow tract. This initiation step is regulated by transcription factors such as AP-2alpha, which is required for cardiac outflow tract morphogenesis. Endothelin signaling also plays a role in preparing these cells for migration.
Guidance by endothelin-Cdc42 signaling
In simple terms: A molecular signal called endothelin activates Cdc42 to steer the moving cells.
Endothelin activates Cdc42, a small GTPase, to regulate neural crest cell migration in the cardiac outflow tract. Disruption of this pathway impairs directed migration and leads to outflow tract defects.
BMPRIA-dependent regulation
In simple terms: BMP signals through its receptor to control the migration and differentiation of neural crest cells.
BMP receptor IA (BMPRIA) is required in mammalian neural crest cells for development of the cardiac outflow tract and ventricular myocardium. Loss of BMPRIA in neural crest cells results in defective outflow tract morphogenesis.
Integrin-linked kinase and cytoskeletal dynamics
In simple terms: Integrin-linked kinase helps the cell's skeleton rearrange so it can move properly.
Integrin-linked kinase is required for neural crest migration and differentiation and for outflow tract morphogenesis. It links extracellular matrix signals to the actin cytoskeleton, and its loss impairs migration.
Epigenetic control by histone deacetylase 3
In simple terms: An enzyme called HDAC3 controls which genes are turned on or off in migrating neural crest cells.
Histone deacetylase 3 regulates smooth muscle differentiation in neural crest cells and development of the cardiac outflow tract. Its loss leads to defective outflow tract formation.
Tissue interactions with endothelial cells
In simple terms: Endothelial cells in the heart help guide the migrating neural crest cells.
Endothelial cells regulate neural crest and second heart field morphogenesis. Signals from endothelial cells influence the migration and behavior of cardiac neural crest cells during outflow tract development.
Key Genes Involved in GO:1905310 regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis
The following genes and proteins are experimentally validated regulators of cardiac neural crest cell migration involved in outflow tract morphogenesis.
| Gene | Major Role | Research Relevance |
|---|---|---|
| Edn1 | Endothelin ligand that activates Cdc42 signaling | Regulates neural crest cell migration in the outflow tract |
| Cdc42 | Small GTPase mediating cytoskeletal changes during migration | Activated by endothelin to control migration |
| Bmpr1a | BMP receptor IA required in neural crest cells | Essential for outflow tract and ventricular myocardium development |
| Ilk | Integrin-linked kinase linking matrix to cytoskeleton | Required for neural crest migration and differentiation |
| Tfap2a | AP-2alpha transcription factor | Required for cardiac outflow tract morphogenesis |
| Hdac3 | Histone deacetylase 3 | Regulates smooth muscle differentiation in neural crest cells |
| Numb | Numb family proteins | Novel players in cardiac morphogenesis and progenitor differentiation |
| Numbl | Numb-like protein | Implicated in cardiac morphogenesis |
| Pax3 | Neural crest specifier | Broadly required for neural crest development |
| Sox10 | Neural crest transcription factor | Maintains neural crest identity during migration |
| Foxd3 | Neural crest transcription factor | Regulates neural crest multipotency |
| Snai1 | EMT regulator | Promotes neural crest delamination |
| Snai2 | EMT regulator | Promotes neural crest delamination |
| Tgfb2 | TGF-beta ligand | Influences outflow tract development |
| Notch1 | Notch receptor | Regulates neural crest cell fate |
| Jag1 | Notch ligand | Associated with outflow tract defects |
| Gata6 | Transcription factor | Regulates outflow tract morphogenesis |
How Is regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis Regulated?
The process is regulated by multiple signaling pathways. Endothelin signaling activates Cdc42 to control migration. BMPRIA signaling is required in neural crest cells for outflow tract development. Integrin-linked kinase mediates cytoskeletal dynamics. Epigenetic regulation by histone deacetylase 3 controls smooth muscle differentiation. Endothelial cells provide additional regulatory cues. Numb family proteins also contribute to cardiac morphogenesis.
regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| Tfap2a | Persistent truncus arteriosus, outflow tract defects | Knockout mouse, CRISPR KO in cell lines |
| Bmpr1a | Outflow tract and ventricular myocardium defects | Conditional knockout mouse |
| Ilk | Neural crest migration defects, outflow tract malformations | CRISPR KO in neural crest cells |
| Hdac3 | Smooth muscle differentiation defects, outflow tract anomalies | Conditional knockout mouse |
| Edn1 | Conotruncal heart defects | CRISPR point mutation in cell models |
Conotruncal heart defects
Disruption of cardiac neural crest cell migration causes conotruncal heart defects such as persistent truncus arteriosus and tetralogy of Fallot. AP-2alpha deficiency leads to outflow tract malformations. BMPRIA loss in neural crest cells results in outflow tract defects.
DiGeorge syndrome and 22q11.2 deletion
Cardiac neural crest cell migration defects are associated with 22q11.2 deletion syndrome, which includes conotruncal anomalies. The term helps annotate genes in this region.
Other congenital heart diseases
Integrin-linked kinase and HDAC3 mutations or loss of function contribute to outflow tract malformations [4,6]. Endothelin-Cdc42 signaling defects also impair migration.
From regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate cardiac neural crest cell migration? | CRISPR knockout in neural crest cell lines or mouse embryos [2,4,5] |
| Does a specific point mutation in gene X alter migration? | CRISPR point mutation knock-in in cell lines [2,4] |
| Does overexpression of gene X enhance migration? | CRISPR overexpression or lentiviral overexpression [2,6] |
| Where is gene X expressed during outflow tract development? | Tagged knock-in with fluorescent reporter [1,7] |
| What are the downstream targets of gene X? | RNA-seq and proteomics after CRISPR KO [3,6] |
| Can gene X rescue migration defects? | Knock-in rescue experiments [4,5] |
How to Study the regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live imaging | Migration speed, directionality, pathfinding | Visualizing neural crest migration in embryos [1,7] |
| RNA-seq | Transcriptome changes | Identifying downstream targets of regulators [3,6] |
| Proteomics | Protein expression and modifications | Mapping signaling changes [2,5] |
| Lineage tracing | Cell fate and contribution | Tracking neural crest derivatives [1,4,5] |
| Immunohistochemistry | Protein localization | Validating expression patterns |
| In situ hybridization | mRNA localization | Detecting gene expression in embryos [1,8] |
| CRISPR screening | Gene function at scale | Identifying novel regulators [2,4,5] |
Live imaging of neural crest cell migration
Time-lapse fluorescence microscopy in transgenic embryos or cell cultures allows direct visualization of cardiac neural crest cell migration and quantification of speed, directionality, and pathfinding [1,7].
Transcriptomics and RNA-seq
RNA sequencing of sorted neural crest cells or microdissected outflow tracts identifies gene expression changes upon perturbation of candidate regulators [3,6].
Proteomics and phosphoproteomics
Mass spectrometry-based proteomics can reveal signaling changes downstream of endothelin-Cdc42 or BMPRIA pathways [2,5].
Genetic lineage tracing
Cre-loxP lineage tracing in mice marks cardiac neural crest cells and their derivatives, enabling assessment of migration and differentiation defects [1,4,5].
How CRISPR Can Be Used to Study GO:1905310 regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis
Knockout
CRISPR knockout of candidate genes such as Edn1, Cdc42, Bmpr1a, Ilk, Tfap2a, or Hdac3 in neural crest cell lines or mouse embryos can test their requirement for cardiac neural crest cell migration and outflow tract morphogenesis [2,4,5,6,8].
Point Mutation
CRISPR point mutation knock-in can model specific human variants in genes like Tfap2a or Bmpr1a to assess their impact on migration and outflow tract development [5,8].
Knock-in
Tagged knock-in of fluorescent reporters (e.g., GFP) into endogenous loci allows real-time visualization of neural crest cell migration and protein localization [1,7].
Overexpression
CRISPR activation or lentiviral overexpression of genes such as Edn1 or Cdc42 can test gain-of-function effects on migration and outflow tract morphogenesis [2,6].
How EDITGENE Supports regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis Research
Researchers studying regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis-related genes often need to determine whether a candidate gene is causally involved in migration and outflow tract development. EDITGENE provides comprehensive CRISPR services to generate precisely engineered cell and animal models for functional validation.
Contact EDITGENE today to design your custom CRISPR model for regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis research.
Frequently Asked Questions About regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis
What is GO:1905310?
GO:1905310 is a Gene Ontology biological process term for regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis.
What genes are involved in regulation of cardiac neural crest cell migration?
Key genes include Edn1, Cdc42, Bmpr1a, Ilk, Tfap2a, and Hdac3 [2,4,5,6,8].
Why is cardiac neural crest cell migration important?
It is essential for outflow tract septation; defects cause conotruncal heart defects [1,5,8].
What diseases are linked to defective cardiac neural crest migration?
Persistent truncus arteriosus, tetralogy of Fallot, and 22q11.2 deletion syndrome [1,5,8].
How does endothelin regulate neural crest migration?
Endothelin activates Cdc42 to control migration in the cardiac outflow tract.
What is the role of BMPRIA in outflow tract development?
BMPRIA is required in neural crest cells for outflow tract and ventricular myocardium development.
How can CRISPR be used to study this process?
CRISPR knockout, point mutation, knock-in, and overexpression models can test gene function in migration and outflow tract morphogenesis [2,4,5,6,8].
What methods are used to study cardiac neural crest migration?
Live imaging, RNA-seq, proteomics, lineage tracing, and immunohistochemistry [1,3,6,7].
What is the role of integrin-linked kinase in neural crest migration?
It links matrix signals to the cytoskeleton and is required for migration and differentiation.
How does HDAC3 regulate outflow tract development?
HDAC3 regulates smooth muscle differentiation in neural crest cells and outflow tract formation.
Conclusion
GO:1905310 provides a precise framework for studying the regulatory mechanisms that control cardiac neural crest cell migration during outflow tract morphogenesis. Experimental evidence implicates endothelin-Cdc42, BMPRIA, integrin-linked kinase, AP-2alpha, and HDAC3 in this process [2,4,5,6,8]. Defects in these pathways cause severe congenital heart defects, making this term highly relevant to developmental biology and disease research [1,5,8]. CRISPR-based models are powerful tools to dissect the causal roles of candidate genes in this process. EDITGENE offers comprehensive services to generate knockout, point-mutation, knock-in, and overexpression models, as well as library screening and bioinformatics support, to accelerate research on regulation of cardiac neural crest cell migration in outflow tract morphogenesis.
References
- 1. Yamagishi H. 2021. Cardiac Neural Crest.. Cold Spring Harb Perspect Biol 13(1) PMID: 32071091
- 2. Fritz KR et al.. 2019. Cdc42 activation by endothelin regulates neural crest cell migration in the cardiac outflow tract.. Dev Dyn 248(9):795-812 PMID: 31219639
- 3. Wu M et al.. 2015. Numb family proteins: novel players in cardiac morphogenesis and cardiac progenitor cell differentiation.. Biomol Concepts 6(2):137-48 PMID: 25883210
- 4. Dai X et al.. 2013. Requirement for integrin-linked kinase in neural crest migration and differentiation and outflow tract morphogenesis.. BMC Biol 11:107 PMID: 24131868
- 5. Stottmann RW et al.. 2004. BMP receptor IA is required in mammalian neural crest cells for development of the cardiac outflow tract and ventricular myocardium.. Development 131(9):2205-18 PMID: 15073157
- 6. Singh N et al.. 2011. Histone deacetylase 3 regulates smooth muscle differentiation in neural crest cells and development of the cardiac outflow tract.. Circ Res 109(11):1240-9 PMID: 21959220
- 7. Milgrom-Hoffman M et al.. 2014. Endothelial cells regulate neural crest and second heart field morphogenesis.. Biol Open 3(8):679-88 PMID: 24996922
- 8. Brewer S et al.. 2002. Requirement for AP-2alpha in cardiac outflow tract morphogenesis.. Mech Dev 110(1-2):139-49 PMID: 11744375
