GO:0001843 neural tube closure: Morphogenetic Mechanisms, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0001843 neural tube closure is the final step of neural tube formation, in which the paired neural folds are brought together and fuse at the dorsal midline.
• Closure depends on convergent extension, apical constriction, actomyosin contractility, and planar cell polarity signaling that coordinate morphogenetic movements.
• Failure of neural tube closure causes neural tube defects such as spina bifida and anencephaly, among the most common human congenital malformations.
• Human embryos may use a single-site closure pattern rather than the multi-site model previously assumed, which changes how closure initiation is studied.
• Maternal metabolism, including folate, glucose, and one-carbon status, strongly influences closure success and neural tube defect risk.
• CRISPR knockout, point-mutation, knock-in, and overexpression models allow causal testing of candidate genes in neural tube closure.
Description
Neural tube closure is the terminal morphogenetic event of neurulation, in which the neural plate elevates, folds, and fuses at the dorsal midline to form the closed neural tube. This process is annotated as GO:0001843 neural tube closure, a biological process defined as the last step in neural tube formation, where the paired neural folds are brought together and fuse at the dorsal midline. Because the neural tube gives rise to the brain and spinal cord, errors in closure produce severe congenital defects, and the process is therefore a central topic in developmental biology and clinical genetics.
neural tube closure At A Glance
| GO ID | GO:0001843 |
|---|---|
| GO term | neural tube closure |
| Ontology | biological_process |
| Synonym | None listed in QuickGO |
| Major function | Bringing paired neural folds together and fusing them at the dorsal midline to complete neural tube formation |
| Related processes | Convergent extension, apical constriction, actomyosin contractility, planar cell polarity signaling |
| Human relevance | Failure causes neural tube defects such as spina bifida and anencephaly |
| Model systems | Mouse, Xenopus, zebrafish, and human embryo studies |
What Is GO:0001843?
GO:0001843 neural tube closure describes the final step in neural tube formation, in which the paired neural folds are brought together and fuse at the dorsal midline. It encompasses the cellular and biomechanical events that convert an open neural plate into a sealed neural tube, including fold elevation, midline apposition, and fusion.
Why Is neural tube closure Important in Cell Biology?
Neural tube closure is essential because it completes the formation of the central nervous system; when closure fails, the resulting neural tube defects are among the most common and severe congenital malformations in humans. Understanding the cellular, molecular, and biomechanical control of closure informs prevention strategies, genetic counseling, and the development of experimental models for candidate gene testing.
• Closure completes neurulation and establishes the closed neural tube that becomes the brain and spinal cord.
• Neural tube defects, including spina bifida and anencephaly, arise from closure failure and are a major cause of infant mortality and disability.
• Planar cell polarity signaling controls the morphogenetic movements required for closure, linking cell polarity to tissue shape.
• Maternal metabolism, including folate and one-carbon status, modifies closure success and neural tube defect risk.
• Human embryo studies suggest closure patterns may differ from classical multi-site models, affecting how initiation is interpreted.
• Cellular mechanisms such as apical constriction and actomyosin contraction provide targets for mechanistic experiments.
• Biomechanical forces generated by surrounding tissues contribute to fold elevation and fusion.
• Genetic and environmental interactions make closure a model for multifactorial disease research.
• Conserved mechanisms across vertebrates allow cross-species validation of candidate genes.
• CRISPR-based models enable causal testing of genes implicated in closure and neural tube defects.
What Happens During neural tube closure?
Neural plate elevation and folding
In simple terms: The flat neural plate bends upward to form folds on each side.
Neural tube closure begins with elevation of the neural folds, driven by intrinsic and extrinsic forces that shape the neural plate into a groove. These movements require coordinated changes in cell shape and tissue mechanics, and they set the stage for the paired folds to approach the dorsal midline.
Convergent extension and midline apposition
In simple terms: Cells move inward and lengthen the tissue so the two folds can meet in the middle.
Convergent extension narrows and elongates the neural plate, bringing the neural folds toward the dorsal midline. Planar cell polarity signaling coordinates this polarized cell movement, and disruption of this pathway impairs closure.
Apical constriction and actomyosin contractility
In simple terms: Cells squeeze their tops to help the tissue bend and close.
Apical constriction, powered by actomyosin contraction, contributes to bending of the neural plate and to the mechanical forces needed for fold apposition. Xenopus studies link planar cell polarity to actomyosin contractions during closure, providing a vertebrate model for these events.
Midline fusion and sealing
In simple terms: The two folds touch and fuse to seal the neural tube.
The final step is fusion of the paired neural folds at the dorsal midline, which seals the neural tube. Human embryo analyses have revisited closure patterns and support a single-site closure model in humans, refining how fusion initiation is understood.
Metabolic and environmental modulation
In simple terms: Nutrition and metabolism influence whether closure succeeds.
Embryonic and maternal metabolism influence neural tube closure, and metabolic status is a recognized modifier of neural tube defect risk. These inputs act alongside genetic programs to determine closure outcome.
Key Genes Involved in GO:0001843 neural tube closure
The following genes and pathways have been implicated in neural tube closure and neural tube defect biology in the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| VANGL1 | Planar cell polarity signaling component | Candidate for closure defects and polarity studies |
| VANGL2 | Planar cell polarity signaling component | Model for convergent extension and closure |
| CELSR1 | Planar cell polarity coreceptor | Studied in neural tube closure and defects |
| SCRIB | Polarity regulator | Links polarity to morphogenesis |
| PARD3 | Apical polarity complex component | Apical constriction and closure studies |
| ROCK1 | Actomyosin contractility regulator | Mechanical control of closure |
| MYH9 | Non-muscle myosin heavy chain | Actomyosin contraction during closure |
| MTHFR | One-carbon and folate metabolism | Maternal metabolism and neural tube defect risk |
| MTR | Methionine synthase | One-carbon metabolism in closure |
| FOLR1 | Folate receptor | Folate uptake and closure success |
| SHH | Ventral patterning signal | Neural tube patterning context |
| BMP4 | Dorsal patterning signal | Neural tube patterning context |
| PAX3 | Neural crest and dorsal neural tube | Closure-related developmental studies |
| GDF7 | Roof plate signaling | Dorsal midline biology |
| WNT5A | Non-canonical Wnt ligand | Planar cell polarity and closure |
| PTK7 | Wnt/planar cell polarity coreceptor | Convergent extension and closure |
| DVL2 | Wnt signaling mediator | Polarity and morphogenesis |
How Is neural tube closure Regulated?
Neural tube closure is regulated by planar cell polarity signaling, which controls polarized cell behaviors and morphogenetic movements during closure. Actomyosin contractility and apical constriction provide mechanical regulation of fold bending and fusion. In addition, maternal and embryonic metabolism, including one-carbon and folate-related pathways, modulate closure and influence neural tube defect risk.
neural tube closure and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| VANGL1 | Neural tube defects and polarity-related closure failure | Knockout and point-mutation models |
| VANGL2 | Closure defects linked to planar cell polarity | Knockout and rescue models |
| MTHFR | Altered folate metabolism and neural tube defect risk | Point-mutation knock-in models |
| FOLR1 | Folate transport and closure failure | Knockout and overexpression models |
| CELSR1 | Polarity signaling and neural tube defects | Knockout and tagged knock-in models |
Neural tube defects
Failure of neural tube closure causes neural tube defects, including spina bifida and anencephaly, which are among the most common congenital malformations and a major cause of infant mortality and disability. Both genetic and environmental factors, including maternal metabolic status, contribute to risk.
Maternal metabolic influences
Maternal metabolism influences neural tube closure, and perturbations in one-carbon and folate-related pathways are associated with altered neural tube defect risk. These findings support prevention strategies and motivate studies of metabolic modifiers in model systems.
Human closure patterns and clinical interpretation
Reanalysis of human embryos supports a single-site neural tube closure model, which affects how closure initiation and defect origins are interpreted clinically. This has implications for understanding which closure sites are most vulnerable in human development.
From neural tube closure-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a candidate gene required for neural tube closure? | CRISPR knockout in mouse or Xenopus |
| Does a specific variant alter closure? | Point-mutation knock-in |
| Where and when is a protein expressed during closure? | Tagged knock-in and imaging |
| Does overexpression of a polarity gene disrupt closure? | Overexpression models |
| How does metabolism influence closure? | Maternal diet and metabolic perturbation models |
| What is the human closure pattern? | Human embryo analysis |
How to Study the neural tube closure Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Gene requirement | Testing candidate closure genes |
| Point-mutation knock-in | Variant effect | Modeling human variants |
| Live imaging | Tissue movements | Fold elevation and fusion |
| Morphometrics | Shape changes | Convergent extension analysis |
| Metabolic profiling | Metabolite levels | Maternal metabolism studies |
| Human embryo analysis | Closure pattern | Human relevance |
| Genetic association | Risk variants | Neural tube defect genetics |
Genetic and CRISPR perturbation
CRISPR knockout, point-mutation, and knock-in approaches allow causal testing of genes implicated in neural tube closure. These methods complement classical vertebrate models such as Xenopus and mouse.
Imaging and morphometrics
Live imaging and morphometric analysis reveal fold elevation, convergent extension, and fusion dynamics during closure. Xenopus provides a tractable system linking planar cell polarity to actomyosin contractions.
Metabolic and nutritional studies
Metabolic profiling and dietary manipulation assess how maternal and embryonic metabolism influence closure and neural tube defect risk.
Human embryo and clinical genetics
Human embryo studies and genetic association analyses inform closure patterns and candidate gene relevance in humans.
How CRISPR Can Be Used to Study GO:0001843 neural tube closure
Knockout
CRISPR knockout is used to test whether a candidate gene is required for neural tube closure, often in mouse or Xenopus models.
Point Mutation
Point-mutation knock-in models introduce specific variants to assess their impact on closure and neural tube defect risk.
Knock-in
Tagged knock-in allows visualization and biochemical analysis of proteins during closure.
Overexpression
Overexpression models test whether excess activity of polarity or signaling genes disrupts closure.
How EDITGENE Supports neural tube closure Research
Researchers studying neural tube closure-related genes often need to determine whether a candidate gene is causally involved, which requires precise genetic models and functional readouts.
Contact EDITGENE today to design your custom CRISPR model for neural tube closure research.
Frequently Asked Questions About neural tube closure
What is GO:0001843 neural tube closure?
GO:0001843 neural tube closure is the biological process defined as the last step in neural tube formation, where the paired neural folds are brought together and fuse at the dorsal midline.
What genes are involved in neural tube closure?
Genes in planar cell polarity signaling such as VANGL1, VANGL2, CELSR1, and PTK7, as well as metabolic genes such as MTHFR and FOLR1, have been implicated.
Why is neural tube closure important?
It completes formation of the central nervous system, and failure causes neural tube defects such as spina bifida and anencephaly.
What causes neural tube defects?
Neural tube defects result from failure of closure and involve genetic and environmental factors, including maternal metabolic status.
How is neural tube closure studied?
It is studied using genetic models, imaging, morphometrics, and metabolic analyses in vertebrates such as mouse and Xenopus.
Does planar cell polarity control neural tube closure?
Yes, planar cell polarity signaling controls morphogenetic movements required for closure.
What is the human neural tube closure pattern?
Human embryo analyses support a single-site closure model.
How does maternal metabolism affect closure?
Maternal metabolism, including folate and one-carbon pathways, influences closure and neural tube defect risk.
Can CRISPR be used to study neural tube closure?
Yes, CRISPR knockout, point-mutation, knock-in, and overexpression models are used to test candidate genes.
What are the main cellular mechanisms of closure?
Convergent extension, apical constriction, actomyosin contractility, and midline fusion are key mechanisms.
Conclusion
Neural tube closure (GO:0001843) is a tightly regulated morphogenetic process that completes neural tube formation through fold elevation, convergent extension, actomyosin-driven bending, and midline fusion. Its failure causes neural tube defects, making it a critical area for genetic, metabolic, and biomechanical research. CRISPR-based models and cross-species studies continue to clarify the genes and mechanisms that control closure.
References
- 1. Nikolopoulou E et al.. 2017. Neural tube closure: cellular, molecular and biomechanical mechanisms.. Development 144(4):552-566 PMID: 28196803
- 2. Greene ND et al.. 2014. Neural tube defects.. Annu Rev Neurosci 37:221-42 PMID: 25032496
- 3. Shi DL. 2022. Wnt/planar cell polarity signaling controls morphogenetic movements of gastrulation and neural tube closure.. Cell Mol Life Sci 79(12):586 PMID: 36369349
- 4. Keuls RA et al.. 2023. Maternal metabolism influences neural tube closure.. Trends Endocrinol Metab 34(9):539-553 PMID: 37468429
- 5. Yamaguchi Y et al.. 2017. Neural tube closure and embryonic metabolism.. Congenit Anom (Kyoto) 57(5):134-137 PMID: 28295633
- 6. Qarawani L et al.. 2025. Regulating closure of the neural tube in humans.. Elife 14 PMID: 40955787
- 7. de Bakker BS et al.. 2017. Single-site neural tube closure in human embryos revisited.. Clin Anat 30(7):988-999 PMID: 28795440
- 8. Matsuda M et al.. 2021. Xenopus neural tube closure: A vertebrate model linking planar cell polarity to actomyosin contractions.. Curr Top Dev Biol 145:41-60 PMID: 34074535
