PDF(Pubmed)
Abstract：
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.
摘要：
覆盖封闭神经管(NT)的表面外胚层(SE)的单个细胞层在哺乳动物NT闭合(NTC)过程中起着至关重要的生物力学作用,挑战先前的假设，即它仅对产生力的神经上皮（NE）是被动的。NTC的失败会导致先天性畸形，称为NT缺陷（NTDs），分别包括脊柱和大脑的脊柱裂（SB）和无脑畸形。在几种小鼠NTD模型中，SB是由SE特异性基因的错误表达引起的，并且与破坏的SE力学有关，包括房尾细胞伸长的丧失被认为对成功闭合很重要。在这项研究中,我们询问SE力学如何影响NT形态，以及在正在进行的闭合位点处的特征性rostrocaudal细胞伸长是否是对SE中的张力各向异性的响应。我们表明，在子宫外小鼠胚胎培养中阻断SE特异性E-cadherin会影响NT形态，以及F-肌动蛋白电缆。细胞边界消融显示细胞形状不是由于张力各向异性,但SE紧张局势存在地区差异。我们还发现YAP核易位反映了区域紧张异质性，并且其表达对张力的药理学降低敏感。总之,我们的结果证实了SE是脊柱NT形态发生的重要生物力学组织,并提示了细胞张力的空间调节的可能作用,其可以通过机械敏感性YAP活性调节下游基因表达.
