Sampath K, Rubinstein A L, Cheng A M, Liang J O, Fekany K, Solnica-Krezel L, Korzh V, Halpern M E, Wright C V
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Nature. 1998 Sep 10;395(6698):185-9. doi: 10.1038/26020.
Zebrafish cyclops (cyc) mutations cause deficiencies in the dorsal mesendoderm and ventral neural tube, leading to neural defects and cyclopia. Here we report that cyc encodes a transforming growth factor-beta (TGF-beta)-related intercellular signalling molecule that is similar to mouse nodal. cyc is expressed in dorsal mesendoderm at gastrulation and in the prechordal plate until early somitogenesis. Expression reappears transiently in the left lateral-plate mesoderm, and in an unprecedented asymmetric pattern in the left forebrain. Injection of cyc RNA non-autonomously restores sonic hedgehog-expressing cells of the ventral brain and floorplate that are absent in cyc mutants, whereas inducing activities are abolished by cyc, a mutation of a conserved cysteine in the mature ligand. Our results indicate that cyc provides an essential non-cell-autonomous signal at gastrulation, leading to induction of the floorplate and ventral brain.
斑马鱼独眼畸形(cyc)突变会导致背侧中胚层和腹侧神经管出现缺陷,从而引发神经缺陷和独眼畸形。我们在此报告,cyc编码一种与转化生长因子-β(TGF-β)相关的细胞间信号分子,该分子与小鼠的节点蛋白相似。cyc在原肠胚形成期的背侧中胚层以及前索板中表达,直至早期体节形成。其表达在左侧侧板中胚层短暂重现,并以前所未有的不对称模式出现在左前脑。注射cyc RNA能非自主性地恢复cyc突变体中缺失的腹侧脑和底板中表达音猬因子的细胞,而成熟配体中一个保守半胱氨酸的突变(cyc突变)会消除诱导活性。我们的结果表明,cyc在原肠胚形成期提供了一种必不可少的非细胞自主性信号,从而诱导底板和腹侧脑的形成。