The zebrafish-secreted matrix protein you/Scube2 is implicated in long-range regulation of Hedgehog signaling
The zebrafish-secreted matrix protein you/Scube2 is implicated in long-range regulation of Hedgehog signaling
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DOI：
10.1016/j.cub.2005.02.018
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发表时间：
2005-03-08
期刊：
影响因子：
9.2
通讯作者：
Okamoto, H
中科院分区：
文献类型：
--
作者：
Kawakami, A;Nojima, Y;Okamoto, H
Hedgehog（Hh）信号在脊椎动物发育期间在中线周围的腹侧神经元和肌肉细胞类型的诱导中起关键作用[1]。我们报告说，在斑马鱼突变体，其中Hh信号受损的基因中断，编码分泌的基质蛋白Scube 2。因此，上位性分析表明，Scube 2的功能Hh配体的上游或通过一个平行的途径。此外，过表达分析表明，Scube 2是一个必不可少的，但在斑马鱼胚胎中的Hh信号的允许，调解人。令人惊讶的是，you基因在背神经管中表达，这增加了Scube 2可能通过Hh信号的远程调节器间接起作用的可能性。背侧BMP对Hh信号传导具有长距离和相反的影响[2-5]。我们表明，神经板图案的影响，在你的突变体的方式是一致的BMP依赖信号的异常远程行动。我们进一步表明，骨形态发生蛋白的活性可以减弱的Scube 2的共表达。我们的数据支持的想法，Scube 2可以调节BMP依赖的信号在神经管和体节的远程行动。
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.