Nectin-2 and N-cadherin interact through extracellular domains and induce apical accumulation of F-actin in apical constriction of Xenopus neural tube morphogenesis
Nectin-2 and N-cadherin interact through extracellular domains and induce apical accumulation of F-actin in apical constriction of Xenopus neural tube morphogenesis
复制标题
DOI：
10.1242/dev.043190
复制
发表时间：
2010-04-15
期刊：
影响因子：
4.6
通讯作者：
Ueno, Naoto
中科院分区：
文献类型：
--
作者：
Morita, Hitoshi;Nandadasa, Sumeda;Ueno, Naoto
神经管的形成是脊椎动物发育中最具活力的形态发生过程之一。然而，调节其起始的分子大多是未知的。在这里，我们表明，nectin-2，免疫球蛋白样细胞粘附分子，参与非洲爪蟾胚胎神经元形成的合作与N-钙粘蛋白。首先，我们发现，在神经形成的开始，nectin-2强烈表达在神经上皮的表面细胞。nectin-2的敲低通过减弱F-肌动蛋白积累和顶端收缩（神经管折叠所需的细胞形状变化）来损害神经折叠的形成。相反，nectin-2在非神经外胚层的过度表达诱导异位顶端收缩与积累的F-肌动蛋白。然而，结构域缺失的连接蛋白-2的实验表明，细胞内的afadin结合基序，连接连接蛋白-2和F-肌动蛋白，是不需要的异位顶端收缩的产生。此外，我们发现，nectin-2的物理相互作用与N-钙粘蛋白通过胞外结构域，他们合作增强顶端收缩驱动积累的F-肌动蛋白在顶端细胞表面。有趣的是，N-钙粘蛋白在神经上皮顶端表面的积累依赖于nectin-2的存在，但nectin-2不受N-钙粘蛋白耗尽的影响。我们提出了一种新的机制，神经管形态发生调节的两种类型的细胞粘附分子。
Neural tube formation is one of the most dynamic morphogenetic processes of vertebrate development. However, the molecules regulating its initiation are mostly unknown. Here, we demonstrated that nectin-2, an immunoglobulin-like cell adhesion molecule, is involved in the neurulation of Xenopus embryos in cooperation with N-cadherin. First, we found that, at the beginning of neurulation, nectin-2 was strongly expressed in the superficial cells of neuroepithelium. The knockdown of nectin-2 impaired neural fold formation by attenuating F-actin accumulation and apical constriction, a cell-shape change that is required for neural tube folding. Conversely, the overexpression of nectin-2 in non-neural ectoderm induced ectopic apical constrictions with accumulated F-actin. However, experiments with domain-deleted nectin-2 revealed that the intracellular afadin-binding motif, which links nectin-2 and F-actin, was not required for the generation of the ectopic apical constriction. Furthermore, we found that nectin-2 physically interacts with N-cadherin through extracellular domains, and they cooperatively enhanced apical constriction by driving the accumulation of F-actin at the apical cell surface. Interestingly, the accumulation of N-cadherin at the apical surface of neuroepithelium was dependent on the presence of nectin-2, but that of nectin-2 was not affected by depletion of N-cadherin. We propose a novel mechanism of neural tube morphogenesis regulated by the two types of cell adhesion molecules.