Division of Morphogenesis, National Institute for Basic Biology, Nishigonaka 38, Myodaiji, Okazaki, Aichi, Japan.
Development. 2012 Apr;139(8):1417-26. doi: 10.1242/dev.073239. Epub 2012 Feb 29.
In developing vertebrates, the neural tube forms from a sheet of neural ectoderm by complex cell movements and morphogenesis. Convergent extension movements and the apical constriction along with apical-basal elongation of cells in the neural ectoderm are thought to be essential for the neural tube closure (NTC) process. In addition, it is known that non-neural ectoderm also plays a crucial role in this process, as the neural tube fails to close in the absence of this tissue in chick and axolotl. However, the cellular and molecular mechanisms by which it functions in NTC are as yet unclear. We demonstrate here that the non-neural superficial epithelium moves in the direction of tensile forces applied along the dorsal-ventral axis during NTC. We found that this force is partly attributable to the deep layer of non-neural ectoderm cells, which moved collectively towards the dorsal midline along with the superficial layer. Moreover, inhibition of this movement by deleting integrin β1 function resulted in incomplete NTC. Furthermore, we demonstrated that other proposed mechanisms, such as oriented cell division, cell rearrangement and cell-shape changes have no or only minor roles in the non-neural movement. This study is the first to demonstrate dorsally oriented deep-cell migration in non-neural ectoderm, and suggests that a global reorganization of embryo tissues is involved in NTC.
在脊椎动物的发育过程中，神经管由一层神经外胚层通过复杂的细胞运动和形态发生形成。人们认为，汇聚延伸运动和细胞在神经外胚层中的顶端收缩以及顶端-基底伸长对于神经管闭合（NTC）过程是必不可少的。此外，已知非神经外胚层在这个过程中也起着至关重要的作用，因为在鸡和蝾螈中，如果没有这种组织，神经管就无法闭合。然而，其在 NTC 中发挥作用的细胞和分子机制尚不清楚。我们在这里证明，在 NTC 过程中，非神经的表面上皮层沿背腹轴方向移动，以适应拉伸力。我们发现，这种力部分归因于非神经外胚层的深层细胞，它们与浅层细胞一起集体向背中线移动。此外，通过删除整合素 β1 功能抑制这种运动导致 NTC 不完全。此外，我们还证明了其他一些被提议的机制，如定向细胞分裂、细胞重排和细胞形状变化，在非神经运动中没有作用或只有很小的作用。这项研究首次证明了非神经外胚层中背向的深层细胞迁移，并表明胚胎组织的整体重组参与了 NTC。
