Cited by 62Developmental Biology and Gene RegulationSpinal Dysraphism and MalformationsNeurogenesis and neuroplasticity mechanisms

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

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Nikolopoulou, Evanthia, Hirst, Caroline S., Galea, Gabriel, Venturini, Christina, Moulding, Dale, Marshall, Abigail R., Rolo, Ana, De Castro, Sandra C. P. +2 more·2019·Nature Communications

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.

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Authors
Nikolopoulou, E., Hirst, C. S., Galea, G., Venturini, C., Moulding, D., Marshall, A. R., Rolo, A., De Castro, S. C. P., Copp, A. J., & Greene, N. D. E.
Affiliations
  • University College London (GB)
  • Horizon Discovery (United Kingdom) (GB)
  • University of Lisbon (PT)
Corresponding author
Greene, Nicholas D. E.
Venue
Nature Communications
Published
2019-06-06
Volume
10
Issue
1
Pages
2487-2487
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2948595072
Cited by
62
References
60
Citations by year
2026: 4 · 2025: 9 · 2024: 7 · 2023: 19 · 2022: 11 · 2021: 7 · 2020: 4
FWCI
1.82
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Wellcome Trust (211112/Z/18/Z, 107474, 087525, /Z/15/Z, 107474/Z/15/Z)
  • NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
  • National Institute for Health and Care Research
  • University College London (087525)
  • Great Ormond Street Hospital for Children
  • Medical Research Council (G0802163)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Spinal Dysraphism and Malformations
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
GRHL2, neural tube closure, neurulation, surface ectoderm, epithelial-mesenchymal transition, N-cadherin, SOX2, actomyosin, cell-cell contact, tissue mechanics, mechanical stress, myosin, transcription factors
MeSH terms
Actomyosin, Animals, Biomechanical Phenomena, Ectoderm, Embryo, Mammalian, Epithelial Cells, Intercellular Junctions, Stress, Mechanical, Transcription Factors, Cadherins, Gene Expression Regulation, Developmental, Neuroepithelial Cells, Mice, Neural Tube, Neurulation, SOXB1 Transcription Factors

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