Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.
Dev Biol. 2012 Aug 15;368(2):193-202. doi: 10.1016/j.ydbio.2012.05.007. Epub 2012 May 17.
The Hedgehog (HH) signaling pathway is a central regulator of embryonic development, controlling the pattern and proliferation of a wide variety of organs. Previous studies have implicated the secreted protein, Scube2, in HH signal transduction in the zebrafish embryo (Hollway et al., 2006; Kawakami et al., 2005; Woods and Talbot, 2005) although the nature of the molecular function of Scube2 in this process has remained undefined. This analysis has been compounded by the fact that removal of Scube2 activity in the zebrafish embryo leads to only subtle defects in HH signal transduction in vivo (Barresi et al., 2000; Hollway et al., 2006; Ochi and Westerfield, 2007; van Eeden et al., 1996; Wolff et al., 2003). Here we present the discovery of two additional scube genes in zebrafish, scube1 and scube3, and demonstrate their roles in facilitating HH signal transduction. Knocking down the function of all three scube genes simultaneously phenocopies a complete loss of HH signal transduction in the embryo, revealing that Scube signaling is essential for HH signal transduction in vivo. We further define the molecular role of scube2 in HH signaling.
刺猬（HH）信号通路是胚胎发育的中央调控者，控制着各种器官的形态和增殖。先前的研究表明，分泌蛋白 Scube2 参与了斑马鱼胚胎中的 HH 信号转导（Hollway 等人，2006 年；Kawakami 等人，2005 年；Woods 和 Talbot，2005 年），尽管 Scube2 在这一过程中的分子功能性质仍未确定。这一分析因以下事实而变得复杂：在斑马鱼胚胎中去除 Scube2 活性只会导致 HH 信号转导在体内出现轻微缺陷（Barresi 等人，2000 年；Hollway 等人，2006 年；Ochi 和 Westerfield，2007 年；van Eeden 等人，1996 年；Wolff 等人，2003 年）。在这里，我们在斑马鱼中发现了另外两个 scube 基因 scube1 和 scube3，并证明了它们在促进 HH 信号转导中的作用。同时敲低这三个 scube 基因的功能会使胚胎中的 HH 信号转导完全缺失，这表明 Scube 信号对于体内的 HH 信号转导是必需的。我们进一步定义了 scube2 在 HH 信号转导中的分子作用。
