Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
Dev Biol. 2013 Aug 1;380(1):37-48. doi: 10.1016/j.ydbio.2013.05.005. Epub 2013 May 15.
Zyxin is a cytoskeletal protein that controls cell movements by regulating actin filaments assembly, but it can also modulate gene expression owing to its interactions with the proteins involved in signaling cascades. Therefore, identification of proteins that interact with Zyxin in embryonic cells is a promising way to unravel mechanisms responsible for coupling of two major components of embryogenesis: morphogenetic movements and cell differentiation. Now we show that in Xenopus laevis embryos Zyxin can bind to and suppress activity of the primary effector of Sonic hedgehog (Shh) signaling cascade, the transcription factor Gli1. By using loss- and gain-of-function approaches, we demonstrate that Zyxin is essential for reduction of Shh signaling within the dorsal part of the neural tube of X. laevis embryo. Thus, our finding discloses a novel function of Zyxin in fine tuning of the central neural system patterning which is based on the ventral-to-dorsal gradient of Shh signaling.
锌指蛋白（Zyxin）是一种细胞骨架蛋白，可通过调节肌动蛋白丝组装来控制细胞运动，但它也可以通过与信号级联中涉及的蛋白质相互作用来调节基因表达。因此，鉴定与胚胎细胞中的 Zyxin 相互作用的蛋白质是揭示负责连接胚胎发生的两个主要成分（形态发生运动和细胞分化）的机制的有前途的方法。现在，我们发现在非洲爪蟾（Xenopus laevis）胚胎中，Zyxin 可以与 Sonic hedgehog（Shh）信号级联的主要效应物转录因子 Gli1 结合并抑制其活性。通过使用失活和获得功能的方法，我们证明 Zyxin 对于减少非洲爪蟾胚胎神经管背部的 Shh 信号是必需的。因此，我们的发现揭示了 Zyxin 在中央神经系统模式形成中的精细调控中的新功能，该功能基于 Shh 信号的腹侧到背侧梯度。
