GO:0061713 anterior neural tube closure: Developmental Process, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0061713 anterior neural tube closure is the biological process in which the paired anterior neural folds are brought together and fuse at the dorsal midline.
• Failure of anterior neural tube closure causes severe congenital malformations such as anencephaly and craniorachischisis.
• Arrayed single-gene perturbation screens in human models have begun to identify specific drivers of anterior neural tube closure.
• Key genes and pathways include folate receptors, Lrp2, Hmmr, and pair-rule-like transcription networks.
• Studying this process requires a combination of CRISPR knockout, point-mutation, knock-in, and overexpression models in appropriate vertebrate systems.
• EDITGENE provides end-to-end CRISPR services to dissect the genetic basis of anterior neural tube closure and related disorders.
Description
Anterior neural tube closure (GO:0061713) is a critical morphogenetic event in early embryogenesis, representing the step where the paired anterior neural folds are brought together and fuse at the dorsal midline. This process is essential for the formation of the brain and cranial structures, and its disruption leads to severe neural tube defects (NTDs) such as anencephaly, which is characterized by the absence of major portions of the brain, skull, and scalp. Understanding the molecular and cellular mechanisms governing anterior neural tube closure is therefore of paramount importance for developmental biology and clinical genetics. Recent advances in functional genomics, including arrayed single-gene perturbation screens, have started to unravel the complex genetic architecture underlying this process in humans. These studies highlight the roles of diverse genes, from folate receptors to endocytic receptors and transcription factors, in ensuring proper neural fold elevation, bending, and fusion. This article provides a comprehensive overview of GO:0061713, integrating authoritative QuickGO definitions with verified PubMed literature to support researchers in designing experiments and interpreting data related to anterior neural tube closure.
anterior neural tube closure At A Glance
| GO ID | GO:0061713 |
|---|---|
| GO term | anterior neural tube closure |
| Ontology | biological_process |
| Synonym | None |
| Definition | The step in the formation of the neural tube, where the paired anterior neural folds are brought together and fuse at the dorsal midline. |
| Major function | Formation of the anterior neural tube, essential for brain and cranial development. |
| Related diseases | Anencephaly, craniorachischisis, neural tube defects. |
| Key genes | FOLR1, LRP2, HMMR, and others identified in screens. |
What Is GO:0061713?
According to the Gene Ontology, anterior neural tube closure (GO:0061713) is defined as the step in the formation of the neural tube where the paired anterior neural folds are brought together and fuse at the dorsal midline. This process is a specialized part of the broader neural tube closure event, specifically occurring in the anterior (cranial) region of the embryo. It involves coordinated cellular movements, changes in cell shape, and precise regulation of gene expression to ensure that the neural ectoderm folds and seals properly, forming the foundation of the central nervous system.
Why Is anterior neural tube closure Important in Cell Biology?
Anterior neural tube closure is a fundamental developmental process whose failure results in some of the most common and severe congenital anomalies in humans, collectively known as neural tube defects (NTDs). Anencephaly, a lethal condition, occurs when the anterior neural tube fails to close, leading to degeneration of the exposed brain tissue. Understanding the genetic and environmental factors that regulate this process is crucial for developing preventive strategies, such as folate supplementation, and for identifying therapeutic targets. Moreover, the molecular mechanisms uncovered in anterior neural tube closure often have broader implications for cell signaling, adhesion, and morphogenesis, making this process a paradigm for studying embryonic development.
• Anterior neural tube closure is essential for normal brain and skull formation; its failure causes anencephaly.
• Neural tube defects are among the most common congenital anomalies, affecting approximately 1 in 1000 births worldwide.
• Folate supplementation reduces the risk of NTDs, highlighting the role of folate receptors in anterior neural tube closure.
• Genes such as Lrp2 and Hmmr have been shown to be critical for anterior neural tube closure in vertebrate models.
• Arrayed single-gene perturbation screens are identifying novel human drivers of anterior neural tube closure.
• Pair-rule-like transcription networks coordinate the spatiotemporal gene expression required for neural tube closure.
• Defects in anterior neural tube closure are associated with both genetic mutations and environmental factors, offering multiple research avenues.
• Studying anterior neural tube closure provides insights into general principles of morphogenesis and epithelial fusion.
• CRISPR-based models enable precise dissection of gene function in anterior neural tube closure.
• Understanding this process can lead to new diagnostic and therapeutic approaches for NTDs.
What Happens During anterior neural tube closure?
Neural Fold Elevation and Bending
In simple terms: The flat sheet of cells that will become the brain starts to fold upward and inward.
The first step in anterior neural tube closure involves the elevation of the neural folds, which are paired ridges of neuroepithelium flanking the neural plate. This elevation is driven by intrinsic cell shape changes and extrinsic forces from surrounding tissues. The neural folds then bend at specific hinge points, such as the dorsolateral hinge points, to bring the folds closer together. Proper bending requires the coordination of cytoskeletal dynamics and cell adhesion, processes that are regulated by genes such as Lrp2, which interacts with intracellular scaffolds to modulate endocytosis and signaling.
Bringing the Anterior Neural Folds Together
In simple terms: The two sides of the folding tissue move toward each other to meet at the midline.
Once elevated and bent, the anterior neural folds must be brought together at the dorsal midline. This step involves complex cell movements and rearrangements, including convergence and extension, which narrow the neural plate and bring the folds into apposition. In Xenopus, the hyaluronan-mediated motility receptor (Hmmr) has been shown to mediate anterior neural tube closure by regulating cell movements and morphogenesis. Disruption of these movements can lead to craniorachischisis, a severe NTD where the neural tube remains open from the brain to the spine.
Fusion of the Neural Folds
In simple terms: The two sides meet and stick together, sealing the tube.
The final step is the fusion of the apposed neural folds, which involves the formation of cell-cell junctions and the remodeling of the epithelial sheets. This process requires the precise regulation of adhesion molecules and cytoskeletal components. Studies in proto-vertebrates have revealed that pair-rule-like transcription patterns coordinate the expression of genes necessary for fusion, ensuring that the neural tube closes at the correct time and place. Failure of fusion results in an open neural tube, leading to anencephaly if the anterior region is affected.
Genetic Control by Folate Receptors
In simple terms: Folate (vitamin B9) helps the tube close, and it needs specific receptors to get into cells.
Folate receptors, such as FOLR1, play a critical role in anterior neural tube closure by mediating the uptake of folate, which is essential for nucleotide synthesis and methylation reactions. Mutations in folate receptor genes have been associated with neural tube defects in humans, and folate supplementation is a proven preventive measure. The exact mechanisms by which folate receptors influence closure are still being investigated, but they likely involve effects on cell proliferation, differentiation, and gene expression.
Identification of Human Drivers
In simple terms: Scientists are using large-scale gene editing screens to find all the genes needed for this process in humans.
Recent arrayed single-gene perturbation screens have begun to systematically identify genes required for human anterior neural tube closure. Huang et al. (2025, 2026) used CRISPR-based perturbations in human cell models to uncover novel drivers of this process, providing a valuable resource for understanding the genetic basis of NTDs. These screens complement traditional animal models and offer insights into human-specific aspects of neural tube closure.
Key Genes Involved in GO:0061713 anterior neural tube closure
The following genes have been experimentally implicated in anterior neural tube closure, based on the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| FOLR1 | Folate receptor 1; mediates folate uptake | Mutations linked to neural tube defects; target for folate supplementation studies |
| LRP2 | Endocytic receptor; interacts with intracellular scaffolds | Required for neural tube closure in mice; regulates morphogen signaling |
| HMMR | Hyaluronan-mediated motility receptor | Mediates anterior neural tube closure in Xenopus; regulates cell movements |
| PAX3 | Transcription factor | Involved in neural tube closure and neural crest development |
| MTHFR | Methylenetetrahydrofolate reductase | Folate metabolism; polymorphisms associated with NTD risk |
| VANGL1 | Planar cell polarity protein | Mutations cause neural tube defects in humans |
| VANGL2 | Planar cell polarity protein | Regulates convergent extension during neural tube closure |
| CELSR1 | Adhesion G-protein coupled receptor | Involved in planar cell polarity and neural tube closure |
| SCRIB | Scaffold protein | Regulates cell polarity and neural tube closure |
| PARD3 | Partitioning defective protein | Cell polarity; required for neural tube closure |
| SHROOM3 | Actin-binding protein | Regulates apical constriction during neural tube closure |
| MARCKS | Membrane-associated protein | Involved in neural tube closure and cell shape changes |
| ROCK1 | Rho-associated kinase | Regulates actomyosin contractility during neural fold elevation |
| CDC42 | Rho GTPase | Controls cytoskeletal dynamics in neural tube closure |
| RAC1 | Rho GTPase | Regulates cell migration and adhesion during closure |
| WNT5A | Secreted signaling molecule | Regulates planar cell polarity and neural tube closure |
| PTK7 | Receptor tyrosine kinase | Involved in planar cell polarity and neural tube closure |
| FZD3 | Frizzled receptor | Wnt signaling; required for neural tube closure |
How Is anterior neural tube closure Regulated?
Anterior neural tube closure is regulated by a complex interplay of genetic and environmental factors. Key signaling pathways include planar cell polarity (PCP) signaling, which controls convergent extension movements essential for neural fold apposition. Folate metabolism is another critical regulator; folate receptors mediate the uptake of folate, which is required for nucleotide synthesis and methylation, and folate supplementation reduces NTD risk. Additionally, pair-rule-like transcription networks have been shown to coordinate the spatiotemporal expression of genes involved in neural tube closure in proto-vertebrates, suggesting an evolutionarily conserved regulatory mechanism. The endocytic receptor Lrp2 and its interaction with intracellular scaffolds also modulate signaling pathways that are crucial for closure.
anterior neural tube closure and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| FOLR1 | Folate-responsive neural tube defects | Knockout mouse, human iPSC-derived neural organoids |
| LRP2 | Craniorachischisis, neural tube defects | Lrp2 knockout mouse, Xenopus morpholino knockdown |
| VANGL1 | Neural tube defects, planar cell polarity | Vangl1 knockout mouse, CRISPR point mutation in human cells |
| VANGL2 | Craniorachischisis, planar cell polarity | Vangl2 knockout mouse, overexpression studies |
| HMMR | Anterior neural tube closure defects | Xenopus knockdown, CRISPR knockout in human cells |
Anencephaly and Craniorachischisis
Failure of anterior neural tube closure leads to anencephaly, a lethal condition characterized by the absence of the forebrain and skull vault, and craniorachischisis, where the neural tube remains open from the brain to the spine. These severe NTDs result from genetic mutations and environmental factors that disrupt the cellular and molecular processes of closure. Mouse models with mutations in genes such as Lrp2 and Vangl1/2 exhibit craniorachischisis, providing insights into the genetic causes.
Folate-Responsive Neural Tube Defects
A significant proportion of neural tube defects are folate-responsive, meaning that maternal folate supplementation can prevent them. Mutations in folate receptor genes, such as FOLR1, can impair folate uptake and increase NTD risk. Understanding the role of folate receptors in anterior neural tube closure is therefore critical for developing targeted interventions and genetic counseling strategies.
Neural Tube Defects and Planar Cell Polarity
Disruptions in planar cell polarity (PCP) signaling components, such as VANGL1, VANGL2, CELSR1, and PTK7, have been associated with neural tube defects in humans and animal models. These genes regulate convergent extension movements that are essential for neural fold apposition. Studying PCP in the context of anterior neural tube closure can reveal new therapeutic targets and diagnostic markers for NTDs.
From anterior neural tube closure-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X cause anterior neural tube closure defects when knocked out? | CRISPR knockout in human iPSCs or mouse embryos |
| Does a specific point mutation in gene X affect neural tube closure? | CRISPR point mutation knock-in in cell lines or animal models |
| How does a tagged version of protein X localize during closure? | CRISPR knock-in of fluorescent tag in human cells or Xenopus |
| Does overexpression of gene X rescue closure defects? | CRISPR overexpression (e.g., CRISPRa) in mutant backgrounds |
| What is the transcriptional profile during anterior neural tube closure? | RNA-seq of microdissected neural folds from model organisms |
| Which genes are essential for human anterior neural tube closure? | Arrayed single-gene perturbation screens in human cell models |
How to Study the anterior neural tube closure Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout screening | Gene essentiality for neural tube closure | Identify novel drivers in human cells |
| RNA-seq | Transcriptional profiles | Compare gene expression across developmental stages |
| Live imaging | Cell movements and tissue morphogenesis | Visualize neural fold elevation and fusion |
| Proteomics | Protein abundance and interactions | Identify complexes regulating closure |
| CRISPR point mutation | Effect of specific variants | Model human NTD-associated mutations |
| CRISPR knock-in tagging | Protein localization and dynamics | Track endogenous proteins during closure |
| CRISPR overexpression | Gain-of-function effects | Test sufficiency of candidate genes |
| Organoid culture | 3D modeling of neural tube closure | Study human-specific aspects in vitro |
CRISPR-Based Functional Genomics
Arrayed single-gene perturbation screens using CRISPR knockout or CRISPR interference (CRISPRi) enable systematic identification of genes required for anterior neural tube closure in human cell models. These screens can be performed in 2D differentiation cultures or 3D organoids that recapitulate aspects of neural tube development. Hits from such screens can be validated using targeted knockout or point mutations.
Transcriptomic Profiling
RNA sequencing (RNA-seq) of neural folds or neural tube tissues at different developmental stages can reveal the dynamic gene expression programs underlying anterior neural tube closure. In proto-vertebrates, pair-rule-like transcription patterns have been identified, highlighting the importance of spatiotemporal regulation. Comparative transcriptomics across species can identify conserved and divergent mechanisms.
Imaging and Morphometrics
Live imaging of neural tube closure in model organisms such as Xenopus, zebrafish, and mouse allows visualization of cell movements, tissue deformation, and fusion events. Fluorescent reporters for cytoskeletal components, adhesion molecules, and signaling proteins can be used to dissect the mechanics of closure. Morphometric analysis quantifies parameters like neural fold angle and closure rate.
Proteomics and Interactomics
Mass spectrometry-based proteomics can identify protein complexes and post-translational modifications that regulate anterior neural tube closure. For example, the interaction between Lrp2 and intracellular scaffolds was elucidated using biochemical and proteomic approaches. Proximity labeling or immunoprecipitation followed by mass spectrometry can reveal dynamic interactomes during closure.
How CRISPR Can Be Used to Study GO:0061713 anterior neural tube closure
Knockout
CRISPR knockout is used to completely ablate candidate genes to assess their requirement for anterior neural tube closure. For example, knocking out LRP2 in mouse models or human cells can recapitulate closure defects and reveal downstream signaling changes. Arrayed knockout screens in human cell models have identified numerous genes essential for this process.
Point Mutation
CRISPR point mutation (base editing or homology-directed repair) allows the introduction of specific disease-associated variants into the genome. This is particularly useful for modeling human NTD-associated mutations in genes like VANGL1 or FOLR1, enabling functional assessment of their impact on anterior neural tube closure.
Knock-in
CRISPR knock-in can be used to insert fluorescent tags, epitope tags, or reporter genes into endogenous loci to study protein localization, dynamics, and interactions during anterior neural tube closure. For instance, tagging HMMR in Xenopus or human cells can reveal its subcellular distribution during neural fold morphogenesis.
Overexpression
CRISPR activation (CRISPRa) or traditional overexpression constructs can drive ectopic expression of candidate genes to test whether they are sufficient to induce or rescue anterior neural tube closure. Overexpression of Hmmr in Xenopus, for example, can affect morphogenesis, and CRISPRa screens can identify genes whose upregulation enhances closure.
How EDITGENE Supports anterior neural tube closure Research
Researchers studying anterior neural tube closure-related genes often need to determine whether a candidate gene is causally involved in the process, and what specific mutations do. EDITGENE provides a comprehensive suite of CRISPR services to accelerate this research, from gene knockout to precise point mutations and large-scale screens.
Contact EDITGENE today to design your custom CRISPR model for anterior neural tube closure research.
Frequently Asked Questions About anterior neural tube closure
What is anterior neural tube closure?
Anterior neural tube closure (GO:0061713) is the developmental process where the paired anterior neural folds are brought together and fuse at the dorsal midline, forming the anterior neural tube.
What genes are involved in anterior neural tube closure?
Key genes include FOLR1, LRP2, HMMR, VANGL1, VANGL2, and many others identified through genetic screens.
What happens if anterior neural tube closure fails?
Failure results in neural tube defects such as anencephaly, a lethal condition where the brain and skull do not form properly.
How is anterior neural tube closure studied?
It is studied using model organisms (mouse, Xenopus, zebrafish), human cell models, CRISPR screens, imaging, and transcriptomics.
What is the role of folate in anterior neural tube closure?
Folate is essential for nucleotide synthesis and methylation; folate receptors mediate its uptake, and supplementation reduces NTD risk.
What are neural tube defects?
Neural tube defects are congenital malformations caused by failure of neural tube closure, including anencephaly and spina bifida.
Which signaling pathways regulate anterior neural tube closure?
Planar cell polarity (PCP) signaling, folate metabolism, and pair-rule-like transcription networks are key regulators.
Can CRISPR be used to study anterior neural tube closure?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are powerful tools for dissecting gene function in this process.
What is the difference between anterior and posterior neural tube closure?
Anterior neural tube closure refers specifically to the fusion of the cranial neural folds, while posterior closure occurs in the spinal region; both are part of neurulation.
What model organisms are best for studying anterior neural tube closure?
Mouse, Xenopus, zebrafish, and proto-vertebrates are commonly used, each offering unique advantages for genetic and imaging studies.
Conclusion
Anterior neural tube closure (GO:0061713) is a fundamental developmental process whose disruption leads to severe congenital malformations. Research over the past decades has identified critical genes and pathways, from folate receptors to planar cell polarity components and pair-rule-like transcription networks. Recent advances in CRISPR-based functional genomics are accelerating the discovery of human-specific drivers of this process. Continued investigation will not only illuminate the basic biology of neurulation but also inform prevention and treatment strategies for neural tube defects.
References
- 1. Bhandari J et al.. 2026. Neural Tube Disorders.. PMID: 32310363
- 2. Huang RE et al.. 2025. Arrayed single-gene perturbations identify drivers of human anterior neural tube closure.. bioRxiv PMID: 40777478
- 3. Saitsu H. 2017. Folate receptors and neural tube closure.. Congenit Anom (Kyoto) 57(5):130-133 PMID: 28244241
- 4. Prager A et al.. 2017. hmmr mediates anterior neural tube closure and morphogenesis in the frog Xenopus.. Dev Biol 430(1):188-201 PMID: 28778799
- 5. Huang RE et al.. 2026. Arrayed single-gene perturbations identify drivers of human anterior neural tube closure.. Elife 14 PMID: 42411605
- 6. Kowalczyk I et al.. 2021. Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds.. Development 148(2) PMID: 33500317
- 7. Östlund-Sholars G et al.. 2025. Pair-rule-like transcription patterns during neural tube closure in a proto-vertebrate.. Development 152(24) PMID: 41217384
- 8. Östlund-Sholars G et al.. 2025. A pair-rule-like transcription network coordinates neural tube closure in a proto-vertebrate.. bioRxiv PMID: 40666853
