State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
J Genet Genomics. 2013 Oct 20;40(10):515-21. doi: 10.1016/j.jgg.2013.07.001. Epub 2013 Aug 8.
Nodal, a member of the transforming growth factor β (TGF-β) superfamily, has been shown to play a role in mesendoderm induction and gastrulation movements. The activity of Nodal signaling can be modulated by microRNAs (miRNAs) as previously reported, but little is known about which miRNAs are regulated by Nodal during gastrulation. In the present study, we found that the expression of mir206, one of the most abundant miRNAs during zebrafish early embryo development, is regulated by Nodal signaling. Abrogation of Nodal signal activity results in defective convergence and extension (CE) movements, and these cell migration defects can be rescued by supplying an excess of mir206, suggesting that mir206 acts downstream of Nodal signaling to regulate CE movements. Furthermore, in mir206 morphants, the expression of cell adhesion molecule E-cadherin is significantly increased, while the key transcriptional repressor of E-cadherin, snail1a, is depressed. Our study uncovers a novel mechanism by which Nodal-regulated mir206 modulates gastrulation movements in connection with the Snail/E-cadherin pathway.
节点蛋白是转化生长因子 β（TGF-β）超家族的成员，已被证明在中胚层诱导和原肠胚运动中发挥作用。如前所述，节点蛋白信号的活性可以被 microRNAs（miRNAs）调节，但在原肠胚形成过程中哪些 miRNAs 受到节点蛋白的调节尚不清楚。在本研究中，我们发现 mir206 的表达，miR206 是斑马鱼早期胚胎发育过程中最丰富的 miRNAs 之一，受到节点蛋白信号的调节。节点蛋白信号活性的阻断导致收敛延伸（CE）运动的缺陷，而过量供应 mir206 可以挽救这些细胞迁移缺陷，表明 mir206 作为节点蛋白信号的下游因子，调节 CE 运动。此外，在 mir206 形态发生缺陷中，细胞黏附分子 E-钙黏蛋白的表达显著增加，而 E-钙黏蛋白的关键转录抑制因子 snail1a 则被抑制。我们的研究揭示了一种新的机制，即节点蛋白调节的 mir206 通过与 Snail/E-cadherin 途径相关，调节原肠胚运动。
