GO:0021915 neural tube development: Embryonic Patterning, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0021915 neural tube development describes the progression of the neural tube from formation to a mature structure segmented into forebrain, midbrain, hindbrain and spinal cord, with neural crest budding away.
• Neural tube closure is a multi-step morphogenetic process driven by apical constriction, convergent extension, and planar cell polarity signaling.
• Failure of neural tube closure causes neural tube defects such as spina bifida and anencephaly, which are among the most common congenital malformations.
• Human pluripotent stem cell and microfluidic models now recapitulate patterned neural tube development and trunk co-development in vitro.
• Key genes include BMP, WNT, FGF, SHH, PAX3, SOX2, and IRF6, which coordinate patterning, closure, and neural crest specification.
• CRISPR knockout, point mutation, knock-in, and overexpression models enable causal testing of neural tube development genes in vitro and in vivo.
Description
Neural tube development (GO:0021915) is the biological process whose specific outcome is the progression of the neural tube over time, from its formation to the mature structure. The mature neural tube is segmented into the forebrain, midbrain, hindbrain and spinal cord regions, and neural crest cells have budded away from the epithelium. This process is foundational for central nervous system formation and is a major focus of developmental biology and congenital disease research. Researchers study neural tube development to understand how patterning signals, morphogenetic movements, and cell fate decisions are coordinated, and to identify the genetic and environmental causes of neural tube defects. Recent advances in organoid and microfluidic models have made it possible to reconstruct patterned human neural tube development in vitro, enabling mechanistic studies that were previously limited to animal models.
neural tube development At A Glance
| GO ID | GO:0021915 |
|---|---|
| GO term | neural tube development |
| Ontology | biological_process |
| Synonym | none |
| Major function | Progression of the neural tube from formation to a mature structure segmented into forebrain, midbrain, hindbrain and spinal cord, with neural crest budding away |
| Related processes | Neural tube closure, convergent extension, planar cell polarity signaling, neural crest specification |
| Disease relevance | Neural tube defects including spina bifida and anencephaly |
| Model systems | Human pluripotent stem cell organoids, microfluidic patterned neural tube models, trunk-like structures |
What Is GO:0021915?
GO:0021915 neural tube development is defined as the process whose specific outcome is the progression of the neural tube over time, from its formation to the mature structure. The mature structure of the neural tube exists when the tube has been segmented into the forebrain, midbrain, hindbrain and spinal cord regions, and neural crest has budded away from the epithelium. In practice, this term covers neural plate induction, neural fold elevation, neural tube closure, regional patterning along the anterior-posterior and dorsal-ventral axes, and the emergence of neural crest cells.
Why Is neural tube development Important in Cell Biology?
Neural tube development is important because it establishes the entire central nervous system and because its failure causes neural tube defects, which are among the most common and severe congenital malformations in humans. Understanding the cellular, molecular and biomechanical mechanisms of neural tube closure provides a basis for genetic counseling, prevention strategies, and the development of stem cell models for disease modeling and drug discovery.
• Neural tube development is the embryonic process that forms the brain and spinal cord.
• Neural tube closure defects cause spina bifida, anencephaly and related congenital malformations.
• Planar cell polarity signaling controls morphogenetic movements required for neural tube closure.
• Neural crest cells, which bud away from the neural tube, contribute to craniofacial structures and peripheral neurons.
• Human organoid and microfluidic models enable mechanistic studies of patterned neural tube development.
• Co-development of somites and neural tube can be modeled in human trunk-like structures.
• Genes such as IRF6 have specific requirements in neural crest and periderm during neural tube and craniofacial development.
• Understanding neural tube development informs prevention and screening strategies for neural tube defects.
What Happens During neural tube development?
Neural plate induction and neural fold formation
In simple terms: The flat sheet of cells that will become the nervous system forms and begins to fold.
Neural tube development begins with induction of the neural plate, a thickened ectodermal sheet that subsequently elevates to form neural folds. Signaling by BMP, WNT and FGF pathways patterns the neural plate and defines the neural versus non-neural ectoderm boundary. The neural folds then elevate and approach each other along the dorsal midline, a process that requires coordinated changes in cell shape and tissue mechanics.
Neural tube closure
In simple terms: The folded edges of the neural plate meet and fuse to create a closed tube.
Neural tube closure is a multi-step process involving apical constriction, cell intercalation, and convergent extension, which together bring the neural folds together and fuse them. Closure initiates at specific sites along the anterior-posterior axis and proceeds bidirectionally, with failure at any step resulting in neural tube defects. Planar cell polarity signaling is a key regulator of the morphogenetic movements that drive closure.
Anterior-posterior and dorsal-ventral patterning
In simple terms: The closed tube is divided into regions that will become the forebrain, midbrain, hindbrain and spinal cord.
After closure, the neural tube is patterned along the anterior-posterior axis into forebrain, midbrain, hindbrain and spinal cord regions, and along the dorsal-ventral axis by opposing SHH and BMP/WNT signals. This patterning establishes distinct progenitor domains that give rise to specific neuronal and glial subtypes. Early spinal cord development from neural tube formation to neurogenesis has been reviewed in detail.
Neural crest delamination
In simple terms: Some cells at the top of the tube break away to form migratory cells that build facial and peripheral structures.
Neural crest cells bud away from the dorsal neural tube epithelium and migrate to diverse destinations, contributing to craniofacial bone and cartilage, peripheral neurons, and melanocytes. Genes such as IRF6 have neural crest-specific and periderm-specific requirements during neural tube and craniofacial development. The budding of neural crest is a defining feature of the mature neural tube as described in GO:0021915.
Co-development with somites and trunk structures
In simple terms: The neural tube develops together with the adjacent somites that form the body wall and muscles.
Neural tube development occurs in coordination with somite formation and trunk morphogenesis, and this co-development can be modeled in human trunk-like structures. Microfluidic gradients have been used to generate patterned human neural tube models that recapitulate key aspects of neural tube development in vitro. These models enable studies of human-specific aspects of neural tube development and defects.
Key Genes Involved in GO:0021915 neural tube development
The following genes and proteins are central to neural tube development, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| BMP4 | Dorsal patterning and neural plate induction | Studied in neural tube patterning and closure models |
| WNT3A | Anterior-posterior patterning and planar cell polarity | Linked to neural tube closure and morphogenetic movements |
| FGF8 | Isthmic organizer and midbrain-hindbrain patterning | Used in neural tube patterning studies |
| SHH | Ventral patterning of the neural tube | Key morphogen in spinal cord and brain development |
| PAX3 | Neural crest and dorsal neural tube specification | Marker of neural crest and neural tube progenitors |
| SOX2 | Neural progenitor maintenance | Used as a neural progenitor marker in organoid models |
| IRF6 | Neural crest and periderm development | Studied in neural tube and craniofacial development |
| VANGL1 | Planar cell polarity signaling | Associated with neural tube closure and defects |
| VANGL2 | Planar cell polarity signaling | Studied in convergent extension and closure |
| CELSR1 | Planar cell polarity signaling | Implicated in neural tube closure |
| SCRIB | Apical constriction and polarity | Studied in neural tube closure models |
| PARD3 | Apical-basal polarity | Required for neural tube morphogenesis |
| CDH1 | Apical adhesion and neural fold fusion | Studied in neural tube closure |
| ROCK1 | Actomyosin contractility | Drives apical constriction during closure |
| MYH9 | Actomyosin contractility | Studied in neural tube morphogenesis |
| TBXT | Somite formation and trunk development | Studied in trunk-like structures with neural tube |
| PAX6 | Neuroepithelial patterning | Marker of neural tube progenitors |
How Is neural tube development Regulated?
Neural tube development is regulated by a combination of secreted morphogens, planar cell polarity signaling, and mechanical forces. WNT/planar cell polarity signaling controls the morphogenetic movements of gastrulation and neural tube closure. BMP, WNT and FGF signals pattern the neural plate and neural tube along multiple axes. Apical constriction and actomyosin contractility are regulated by Rho-ROCK signaling and polarity proteins such as PARD3 and SCRIB. IRF6 has been shown to have neural crest and periderm-specific requirements during neural tube and craniofacial development.
neural tube development and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| VANGL1 | Neural tube defects | Knockout or point mutation in human neural tube organoids |
| VANGL2 | Neural tube defects | Knockout mouse or human iPSC-derived neural tube models |
| IRF6 | Craniofacial and neural crest disorders | Neural crest-specific knockout in organoid models |
| SHH | Holoprosencephaly and neural tube patterning defects | Knockout or knock-in in neural tube organoids |
| TBXT | Trunk and somite-related developmental defects | Trunk-like structure models with neural tube |
Neural tube defects
Failure of neural tube closure causes neural tube defects such as spina bifida and anencephaly, which are among the most common congenital malformations. Genetic studies have identified variants in planar cell polarity genes, including VANGL1 and VANGL2, that are associated with neural tube defects. Environmental factors such as folate status also influence risk, and prevention strategies have been developed based on this understanding.
Craniofacial and neural crest disorders
Because neural crest cells bud away from the neural tube and contribute to craniofacial structures, defects in neural tube development can lead to craniofacial anomalies. IRF6 mutations are associated with craniofacial disorders, and its neural crest-specific requirements have been studied in neural tube and craniofacial development.
Spinal cord and neurodevelopmental disorders
Early spinal cord development from neural tube formation to neurogenesis is critical for motor and sensory function, and disruptions can contribute to neurodevelopmental disorders. Human organoid and microfluidic models of neural tube development provide platforms for studying these conditions.
From neural tube development-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does a candidate gene cause neural tube closure defects? | CRISPR knockout in human neural tube organoids |
| Does a specific variant alter neural tube patterning? | Point mutation knock-in in iPSC-derived neural tube models |
| How does a gene affect neural crest delamination? | Neural crest-specific knockout or overexpression |
| What is the role of a gene in anterior-posterior patterning? | Tagged knock-in for live imaging in microfluidic models |
| Does overexpression of a gene drive neural tube expansion? | Doxycycline-inducible overexpression in neural tube organoids |
| How do somites and neural tube co-develop? | Human trunk-like structures with CRISPR perturbations |
How to Study the neural tube development Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Single-cell RNA sequencing | Cell types and states in neural tube | Patterning and neural crest studies |
| Live imaging | Morphogenetic movements | Neural tube closure dynamics |
| Microfluidic gradient culture | Patterning responses to morphogens | Human neural tube models |
| CRISPR knockout | Loss-of-function effects | Causal gene testing |
| Knock-in reporter | Gene expression and localization | Lineage tracing and live imaging |
| Overexpression | Gain-of-function effects | Signaling pathway activation |
| Trunk-like structure culture | Somite-neural tube co-development | Human trunk morphogenesis |
| Pharmacological inhibition | Pathway requirement | Signaling dissection |
Organoid and microfluidic models
Human pluripotent stem cell-derived neural tube organoids and microfluidic gradient systems recapitulate patterned neural tube development in vitro. These models allow controlled manipulation of signaling gradients and enable live imaging of morphogenetic movements. They are particularly useful for studying human-specific aspects of neural tube development and defects.
Transcriptomics and single-cell RNA sequencing
Single-cell RNA sequencing can resolve cell types and states within developing neural tubes and organoids, revealing patterning trajectories and neural crest emergence. This approach is often combined with CRISPR perturbations to link genes to developmental outcomes.
Imaging and morphometrics
Live imaging of neural tube closure in model organisms and organoids reveals cellular behaviors such as apical constriction and convergent extension. Morphometric analysis quantifies tissue shape changes and closure progression.
Genetic and pharmacological perturbation
Knockout, knock-in and overexpression of candidate genes in animal models and human organoids test causality in neural tube development. Pharmacological inhibitors of WNT, BMP, FGF and SHH pathways are used to dissect signaling requirements.
How CRISPR Can Be Used to Study GO:0021915 neural tube development
Knockout
CRISPR knockout of candidate genes in human neural tube organoids or animal models can test whether a gene is required for neural tube closure and patterning. For example, knockout of planar cell polarity genes such as VANGL1 or VANGL2 can reveal their roles in convergent extension and closure.
Point Mutation
Point mutation knock-in can model specific human variants associated with neural tube defects, allowing assessment of their functional impact on neural tube development. This approach is useful for variant classification and mechanistic studies.
Knock-in
Tagged knock-in of fluorescent reporters or epitope tags enables live imaging and biochemical analysis of neural tube development genes. Knock-in of lineage markers can trace neural crest delamination and migration.
Overexpression
Inducible overexpression of signaling molecules such as WNT, BMP or SHH can drive or disrupt neural tube patterning in organoid models. Overexpression studies help define sufficiency and dosage effects in neural tube development.
How EDITGENE Supports neural tube development Research
Researchers studying neural tube development-related genes often need to determine whether a candidate gene is causally involved in neural tube closure, patterning, or neural crest emergence. EDITGENE provides CRISPR-based cell model services to support these studies with rigorous, reproducible tools.
Contact EDITGENE today to design your custom CRISPR model for neural tube development research.
Frequently Asked Questions About neural tube development
What is GO:0021915 neural tube development?
GO:0021915 neural tube development is the biological process whose specific outcome is the progression of the neural tube from formation to a mature structure segmented into forebrain, midbrain, hindbrain and spinal cord, with neural crest budding away.
What genes are involved in neural tube development?
Key genes include BMP4, WNT3A, FGF8, SHH, PAX3, SOX2, IRF6, VANGL1, VANGL2, CELSR1, SCRIB, PARD3, CDH1, ROCK1, MYH9, TBXT and PAX6.
Why is neural tube closure important?
Neural tube closure is essential for forming the brain and spinal cord, and failure causes neural tube defects such as spina bifida and anencephaly.
What diseases are linked to neural tube development defects?
Neural tube defects, craniofacial disorders, and some neurodevelopmental conditions are linked to disrupted neural tube development.
How can I study neural tube development in the lab?
Human pluripotent stem cell organoids, microfluidic patterned models, trunk-like structures, and CRISPR perturbations are commonly used.
What is the role of planar cell polarity in neural tube closure?
Planar cell polarity signaling controls morphogenetic movements such as convergent extension that are required for neural tube closure.
Can CRISPR be used to model neural tube defects?
Yes, CRISPR knockout, point mutation, knock-in and overexpression models can test causal roles of genes in neural tube development.
What are human neural tube organoids?
Human neural tube organoids are stem cell-derived structures that recapitulate patterned neural tube development in vitro.
How does IRF6 affect neural tube development?
IRF6 has neural crest and periderm-specific requirements during neural tube and craniofacial development.
What is the relationship between somites and neural tube development?
Somites and the neural tube co-develop in the trunk, and this can be modeled in human trunk-like structures.
Conclusion
GO:0021915 neural tube development encompasses the formation, closure, patterning and maturation of the neural tube, a process essential for central nervous system formation. Disruption of this process causes neural tube defects and related congenital disorders, making it a major focus of developmental and disease research. Advances in human organoid and microfluidic models, combined with CRISPR-based perturbations, now enable mechanistic studies of neural tube development with human relevance.
References
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- 2. Nikolopoulou E et al.. 2017. Neural tube closure: cellular, molecular and biomechanical mechanisms.. Development 144(4):552-566 PMID: 28196803
- 3. Li P et al.. 2022. Progress in Modeling Neural Tube Development and Defects by Organoid Reconstruction.. Neurosci Bull 38(11):1409-1419 PMID: 35753025
- 4. Xue X et al.. 2024. A patterned human neural tube model using microfluidic gradients.. Nature 628(8007):391-399 PMID: 38408487
- 5. Makwana K et al.. 2025. Modelling co-development between the somites and neural tube in human trunk-like structures.. Nat Cell Biol 27(12):2049-2062 PMID: 41402467
- 6. Copp AJ et al.. 2010. Genetics and development of neural tube defects.. J Pathol 220(2):217-30 PMID: 19918803
- 7. Carroll SH et al.. 2025. Neural crest and periderm-specific requirements of Irf6 during neural tube and craniofacial development.. Dev Biol 522:106-115 PMID: 40113028
- 8. 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
