1. Spinal neural tube closure depends on regulation of surface ectoderm identity and biomechanics by Grhl2.
- Author
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Nikolopoulou E, Hirst CS, Galea G, Venturini C, Moulding D, Marshall AR, Rolo A, De Castro SCP, Copp AJ, and Greene NDE
- Subjects
- Actomyosin genetics, Actomyosin metabolism, Animals, Biomechanical Phenomena, Cadherins metabolism, Ectoderm cytology, Ectoderm embryology, Ectoderm metabolism, Epithelial Cells metabolism, Intercellular Junctions genetics, Intercellular Junctions metabolism, Mice, Neural Tube metabolism, SOXB1 Transcription Factors metabolism, Stress, Mechanical, Transcription Factors metabolism, Embryo, Mammalian metabolism, Gene Expression Regulation, Developmental, Neural Tube embryology, Neuroepithelial Cells metabolism, Neurulation genetics, Transcription Factors genetics
- Abstract
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.
- Published
- 2019
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