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

Evanthia Nikolopoulou, Caroline S. Hirst, Gabriel Galea, Christina Venturini, Dale Moulding, Abigail R. Marshall, Ana Rolo, Sandra C. P. Castro, Andrew J. Copp and Nicholas D. E. Greene ()
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Evanthia Nikolopoulou: UCL Great Ormond Street Institute of Child Health, University College London
Caroline S. Hirst: UCL Great Ormond Street Institute of Child Health, University College London
Gabriel Galea: UCL Great Ormond Street Institute of Child Health, University College London
Christina Venturini: UCL Infection and Immunity Division, UCL Pathogen Genomic Unit, UCL Cruciform Building
Dale Moulding: UCL Great Ormond Street Institute of Child Health, University College London
Abigail R. Marshall: UCL Great Ormond Street Institute of Child Health, University College London
Ana Rolo: UCL Great Ormond Street Institute of Child Health, University College London
Sandra C. P. Castro: UCL Great Ormond Street Institute of Child Health, University College London
Andrew J. Copp: UCL Great Ormond Street Institute of Child Health, University College London
Nicholas D. E. Greene: UCL Great Ormond Street Institute of Child Health, University College London

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10164-6

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