Spinal neural tube closure depends on regulation of surface ectoderm identity and biomechanics by Grhl2
Year: 2019
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,108
Awards: Cellular mechanisms underlying the morphogenetic biomechanics of mammalian neural tube closure, G3080052052, The cellular mechanobiology of mammalian neural tube closure., Neural tube closure: a biological and computational approach to understanding the developmental and folate-protective mechanisms., G6657272142, G6868616705, The cellular mechanobiology of mammalian neural tube closure.
OpenAlex ID: W2948595072