Kawakami Atsushi, Nojima Yasuhiro, Toyoda Atsushi, Takahoko Mikako, Satoh Miki, Tanaka Hideomi, Wada Hironori, Masai Ichiro, Terasaki Harumi, Sakaki Yoshiyuki, Takeda Hiroyuki, Okamoto Hitoshi
Department of Biological Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Curr Biol. 2005 Mar 8;15(5):480-8. doi: 10.1016/j.cub.2005.02.018.
The Hedgehog (Hh) signal plays a pivotal role in induction of ventral neuronal and muscle cell types around the midline during vertebrate development [1]. We report that the gene disrupted in zebrafish you mutants, in which Hh signaling is impaired, encodes the secreted matrix protein Scube2. Consistently, epistasis analyses suggested that Scube2 functions upstream of Hh ligands or through a parallel pathway. In addition, overexpression analyses suggested that Scube2 is an essential, but a permissive, mediator of Hh signaling in zebrafish embryos. Surprisingly, the you gene is expressed in the dorsal neural tube, raising the possibility that Scube2 could indirectly act via a long-range regulator of Hh signaling. The dorsal Bmps have a long-range and opposing influence on Hh signaling [2-5]. We show that neural plate patterning is affected in you mutants in a way that is consistent with the aberrant long-range action of a Bmp-dependent signal. We further show that Bmp activity can be attenuated by the coexpression of Scube2. Our data support the idea that Scube2 can modulate the long-range action of Bmp-dependent signaling in the neural tube and somites.
在脊椎动物发育过程中，刺猬信号通路（Hh信号通路）在诱导中线周围腹侧神经元和肌肉细胞类型方面起着关键作用[1]。我们报道，在斑马鱼you突变体中被破坏的基因编码分泌型基质蛋白Scube2，在该突变体中Hh信号传导受损。一致地，上位性分析表明Scube2在Hh配体上游发挥作用或通过平行途径发挥作用。此外，过表达分析表明Scube2是斑马鱼胚胎中Hh信号传导的一种必需但非决定性的介质。令人惊讶的是，you基因在背侧神经管中表达，这增加了Scube2可能通过Hh信号传导的远程调节因子间接发挥作用的可能性。背侧骨形态发生蛋白（Bmp）对Hh信号传导具有远程且相反的影响[2-5]。我们表明，you突变体中的神经板模式形成受到影响，其方式与Bmp依赖性信号的异常远程作用一致。我们进一步表明，Scube2的共表达可以减弱Bmp活性。我们的数据支持这样一种观点，即Scube2可以调节神经管和体节中Bmp依赖性信号传导的远程作用。
