Cellular and Molecular Mechanisms of Neural Tube Morphogenesis

Neural tube morphogenesis is the process by which a flat sheet of neuroepithelial cells transforms into a closed tubular structure that gives rise to the brain and spinal cord. This transformation is orchestrated through coordinated cell shape changes, tissue-scale movements and mechanical forces. Key morphogenetic events include apical constriction, whereby actomyosin contractility at the apical cortex of neuroepithelial cells generates wedge-shaped profiles that bend the neural plate; convergent extension, in which mediolateral intercalation narrows and elongates the tissue; and epithelial fusion, by which paired neural folds meet and zipper along the dorsal midline. Underlying these processes are molecular regulators such as Rho GTPases, ROCK kinases, LIM kinases and cofilin, which control actin turnover and myosin activity, and components of the planar cell polarity pathway that bias cells to align their behaviour in the tissue plane. Interactions with adjacent tissues, including the surface ectoderm and mesoderm, and with the extracellular matrix further modulate force transmission and adhesion during closure. Apoptosis and cell proliferation pattern regional growth and tissue stiffness, while gene regulatory networks define regional cell identity and junctional composition. Dysregulation of any of these elements can lead to neural tube defects, highlighting the clinical significance of understanding the interplay between cell-intrinsic mechanics and tissue-level biomechanics.

Research from Nature Portfolio

Recent studies have advanced our quantitative understanding of the forces driving vertebrate neural tube closure. Micrometre-resolution elastic sensors embedded by intravital bioprinting have enabled direct measurement of compression forces generated as neural folds converge, revealing a balance between pro-closure contractility and anti-closure forces mediated by Rho-associated kinase. These findings demonstrate how precise regulation of actomyosin tension is essential for fold apposition. In parallel, work on avian embryos has shown that modulation of extraembryonic tension by the vitelline membrane is critical for timely neural fold elevation and spinal closure. By characterising changes in membrane stiffness and glycoprotein composition linked to pH-driven biochemical shifts, this research highlights how external mechanical constraints interface with intrinsic morphogenetic programmes to ensure robust tube formation.

Cellular and Molecular Mechanisms of Neural Tube Morphogenesis publication trend

The graph below shows the total number of articles in cellular and molecular mechanisms of neural tube morphogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Apical constriction: Narrowing of the apical surface of epithelial cells driven by actomyosin contractility, leading to tissue bending.

Convergent extension: Tissue-scale process in which cells intercalate mediolaterally to elongate and narrow a tissue axis.

Planar cell polarity (PCP): Coordinated orientation of cells within the plane of an epithelial sheet that directs directional cell behaviours.

Extracellular matrix (ECM): Network of proteins and polysaccharides outside cells that provides structural support and mechanical cues.

Neuroepithelium: Early epithelial layer of cells that gives rise to the central nervous system through morphogenetic movements.

References

1. Quantifying mechanical forces during vertebrate morphogenesis. Nature Materials (2024).
2. Downregulation of extraembryonic tension controls body axis formation in avian embryos. Nature Communications (2023).
3. The cellular dynamics of neural tube formation. Biochemical Society Transactions (2023).
4. Somitic mesoderm morphogenesis is necessary for neural tube closure during Xenopus development. Frontiers in Cell and Developmental Biology (2023).
5. Integrin-Mediated Focal Anchorage Drives Epithelial Zippering during Mouse Neural Tube Closure. Developmental Cell (2020).