Cloning of zebrafish nkx6.2 and a comprehensive analysis of the conserved transcriptional response to Hedgehog/Gli signaling in the zebrafish neural tube
Cloning of zebrafish nkx6.2 and a comprehensive analysis of the conserved transcriptional response to Hedgehog/Gli signaling in the zebrafish neural tube
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DOI：
10.1016/j.modgep.2007.01.002
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发表时间：
2007-04-01
影响因子：
1.2
通讯作者：
Karlstrom, Rolf O.
中科院分区：
文献类型：
--
作者：
Guner, Burcu;Karlstrom, Rolf O.
Sonic Hedgehog（Shh）信号传导部分地通过调节含有转录因子的许多同源域的背侧/腹侧表达来帮助脊椎动物神经管的模式化。这些Hh应答基因被分为两类，II类基因被Hh信号激活，I类基因被Hh信号抑制。虽然在鸡和小鼠中对不同Hh水平的转录反应得到了很好的定义，但在斑马鱼中仅部分描述了这一点，尽管斑马鱼已成为研究神经模式的强大遗传系统。为了更好地表征斑马鱼神经管中的Hh反应，我们克隆了斑马鱼II类Hh靶基因nkx2.9和nkx6.2。然后，我们分析了一些I类和II类Hh响应基因在野生型，Hh突变体，Hh过表达斑马鱼胚胎的表达。我们表明，I类和II类基因的表达是高度保守的脊椎动物神经管。此外，在分析的所有Hh途径突变体中，最腹侧的II类基因表达完全丧失，表明高水平的Hh信号传导在所有这些突变体中被阻断。相反，更多的背侧表达的基因在不同的Hh通路突变体中受到不同程度的影响，表明中等水平的Hh信号传导受到不同程度的影响。这项全面的表达研究为表征斑马鱼中Hh信号转导提供了重要工具，并为确定新的Hh信号转导的程度提供了灵敏的测定方法。
Sonic Hedgehog (Shh) signaling helps pattern the vertebrate neural tube, in part by regulating the dorsal/ventral expression of a number of homeodomain containing transcription factors. These Hh responsive genes have been divided into two classes, with Class II genes being activated by Hh signaling and Class I genes being repressed by Hh signaling. While the transcriptional response to varying Hh levels is well defined in chick and mouse, it is only partially described in zebrafish, despite the fact that zebrafish has emerged as a powerful genetic system for the study of neural patterning. To better characterize the Hh response in the zebrafish neural tube, we cloned the zebrafish Class II Hh target genes nkx2.9 and nkx6.2. We then analyzed the expression of a number of Class I and Class II Hh responsive genes in wild type, Hh mutant, and Hh over-expressing zebrafish embryos. We show that expression of Class I and Class II genes is highly conserved in the vertebrate neural tube. Further, ventral-most Class II gene expression was completely lost in all Hh pathway mutants analyzed, indicating high levels of Hh signaling are blocked in all of these mutants. In contrast, more dorsally expressed genes were variably affected in different Hh pathway mutants, indicating mid-levels of Hh signaling are differentially affected. This comprehensive expression study provides an important tool for the characterization of Hh signaling in zebrafish and provides a sensitive assay for determining the degree to which newly