Spinal neural tube closure depends on regulation of surface ectoderm identity and biomechanics by Grhl2

• Published in: Nature communications Vol. 10; no. 1; p. 2487
• Main Authors: Nikolopoulou, Evanthia, Hirst, Caroline S., Galea, Gabriel, Venturini, Christina, Moulding, Dale, Marshall, Abigail R., Rolo, Ana, De Castro, Sandra C. P., Copp, Andrew J., Greene, Nicholas D. E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.06.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 14/19; 14/28; 38; 38/91; 631/136/1425; 631/136/1660; 631/136/2060; 631/136/2086; 64/60; 82/51; Ablation; Actomyosin; Actomyosin - genetics; Actomyosin - metabolism; Animals; Apposition; Biomechanical Phenomena; Biomechanics; Cadherins; Cadherins - metabolism; Cell size; Ectoderm; Ectoderm - cytology; Ectoderm - embryology; Ectoderm - metabolism; Ectopic expression; Embryo, Mammalian - metabolism; Embryos; Epithelial Cells - metabolism; Gene Expression Regulation, Developmental; Humanities and Social Sciences; Intercellular Junctions - genetics; Intercellular Junctions - metabolism; Mechanical properties; Mice; multidisciplinary; Myosin; N-Cadherin; Neural tube; Neural Tube - embryology; Neural Tube - metabolism; Neuroepithelial Cells - metabolism; Neurulation - genetics; Recoil; Science; Science (multidisciplinary); SOXB1 Transcription Factors - metabolism; Stress, Mechanical; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-10164-6

Lack or excess expression of the surface ectoderm-expressed transcription factor Grainyhead-like2 (Grhl2), each prevent spinal neural tube closure. Here we investigate the causative mechanisms and find reciprocal dysregulation of epithelial genes, cell junction components and actomyosin properties in Grhl2 null and over-expressing embryos. Grhl2 null surface ectoderm shows a shift from epithelial to neuroepithelial identity (with ectopic expression of N-cadherin and Sox2), actomyosin disorganisation, cell shape changes and diminished resistance to neural fold recoil upon ablation of the closure point. In contrast, excessive abundance of Grhl2 generates a super-epithelial surface ectoderm, in which up-regulation of cell-cell junction proteins is associated with an actomyosin-dependent increase in local mechanical stress. This is compatible with apposition of the neural folds but not with progression of closure, unless myosin activity is inhibited. Overall, our findings suggest that Grhl2 plays a crucial role in regulating biomechanical properties of the surface ectoderm that are essential for spinal neurulation. Loss or over-expression of Grainyhead-like transcription factors (Grhl) prevents closure of the neural tube but the mechanism underlying this is unclear. Here, the authors show that Grhl2 regulates murine posterior-neuropore closure via changes in the identity and biomechanics of the non-neural, surface ectoderm cells.