PDF(Pubmed)
Abstract：
Neural tube closure is a fundamental process during vertebrate embryogenesis, which leads to the formation of the central nervous system. Defective neural tube closure leads to neural tube defects which are some of the most common human birth defects. While the intrinsic morphogenetic events shaping the neuroepithelium have been studied extensively, how tissues mechanically coupled with the neural plate influence neural tube closure remains poorly understood. Here, using Xenopus laevis embryos, live imaging in combination with loss of function experiments and morphometric analysis of fixed samples we explore the reciprocal mechanical communication between the neural plate and the somitic mesoderm and its impact on tissue morphogenesis. We show that although somitic mesoderm convergent extension occurs independently from neural plate morphogenesis neural tube closure depends on somitic mesoderm morphogenesis. Specifically, impaired somitic mesoderm remodelling results in defective apical constriction within the neuroepithelium and failure of neural tube closure. Last, our data reveal that mild abnormalities in somitic mesoderm and neural plate morphogenesis have a synergistic effect during neurulation, leading to severe neural tube closure defects. Overall, our data reveal that defective morphogenesis of tissues mechanically coupled with the neural plate can not only drastically exacerbate mild neural tube defects that may arise from abnormalities within the neural tissue but can also elicit neural tube defects even when the neural plate is itself free of inherent defects.
摘要：
神经管闭合是脊椎动物胚胎发生过程中的一个基本过程,导致中枢神经系统的形成。有缺陷的神经管闭合导致神经管缺陷，这是一些最常见的人类出生缺陷。虽然形成神经上皮的内在形态发生事件已被广泛研究，与神经板机械耦合的组织如何影响神经管闭合仍知之甚少。这里,利用非洲爪狼胚胎，实时成像结合功能丧失实验和固定样品的形态计量分析，我们探索了神经板和躯体中胚层之间的相互机械交流及其对组织形态发生的影响。我们表明，尽管躯体中胚层收敛延伸的发生与神经板形态发生无关，但神经管闭合取决于躯体中胚层形态发生。具体来说,躯体中胚层重塑受损会导致神经上皮内的根尖收缩缺陷和神经管闭合失败。最后,我们的数据表明，在躯体中胚层和神经板形态发生的轻度异常在神经形成过程中具有协同作用，导致严重的神经管闭合缺陷。总的来说,我们的数据表明，与神经板机械耦合的组织形态发生缺陷不仅可以大大加剧可能由神经组织内异常引起的轻度神经管缺陷，而且即使神经板本身没有固有缺陷，也可以引起神经管缺陷。
