The surface ectoderm exhibits spatially heterogenous tension that correlates with YAP localisation during spinal neural tube closure in mouse embryos

• Published in: Cells & development 2023-06, Vol.174, p.203840-203840, Article 203840
• Main Authors: Marshall, Abigail R., Galea, Gabriel L., Copp, Andrew J., Greene, Nicholas D.E.
• Format: Article
• Language: English
• Subjects: Animals; Biomechanics; Disease Models, Animal; Ectoderm; Laser ablation; Mammals; Mice; Neural Tube; Neural tube closure; Neural Tube Defects - genetics; Spinal Dysraphism - complications; Spinal Dysraphism - genetics; Spine; Surface ectoderm
• ISSN: 2667-2901; 2667-291X; 2667-2901
• DOI: 10.1016/j.cdev.2023.203840

The single cell layer of surface ectoderm (SE) which overlies the closing neural tube (NT) plays a crucial biomechanical role during mammalian NT closure (NTC), challenging previous assumptions that it is only passive to the force-generating neuroepithelium (NE). Failure of NTC leads to congenital malformations known as NT defects (NTDs), including spina bifida (SB) and anencephaly in the spine and brain respectively. In several mouse NTD models, SB is caused by misexpression of SE-specific genes and is associated with disrupted SE mechanics, including loss of rostrocaudal cell elongation believed to be important for successful closure. In this study, we asked how SE mechanics affect NT morphology, and whether the characteristic rostrocaudal cell elongation at the progressing closure site is a response to tension anisotropy in the SE. We show that blocking SE-specific E-cadherin in ex utero mouse embryo culture influences NT morphology, as well as the F-actin cable. Cell border ablation shows that cell shape is not due to tension anisotropy, but that there are regional differences in SE tension. We also find that YAP nuclear translocation reflects regional tension heterogeneity, and that its expression is sensitive to pharmacological reduction of tension. In conclusion, our results confirm that the SE is a biomechanically important tissue for spinal NT morphogenesis and suggest a possible role of spatial regulation of cellular tension which could regulate downstream gene expression via mechanically-sensitive YAP activity. •Disruption of surface ectoderm E-cadherin affects spinal neural tube morphology.•Elongated surface ectoderm cell shape is not due to tension anisotropy.•Surface ectoderm tension is regionally heterogenous as revealed by laser ablation.•YAP nuclear translocation reflects differences in surface ectoderm tension.