Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia
Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia
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DOI：
10.1242/dev.041343
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发表时间：
2009-09-15
期刊：
影响因子：
4.6
通讯作者：
Schier, Alexander F.
中科院分区：
文献类型：
--
作者：
Huang, Peng;Schier, Alexander F.
纤毛在小鼠中参与Hedgehog（Hh）和Wnt信号传导，但在果蝇中不参与。为了确定纤毛的作用是否在斑马鱼中是保守的，我们产生了缺乏所有纤毛的母合子（MZ）卵圆形（ovl; ift 88）突变体。MZovl突变体显示正常的经典和非经典Wnt信号传导，但显示Hh信号传导的缺陷。与小鼠一样，斑马鱼纤毛需要介导Hh、Ptc、Smo和PKA的活性。然而，与小鼠Ift 88突变体（其显示出Hh信号传导的显著降低）相反，斑马鱼MZovl突变体显示出抑制但扩大的Hh途径活性。这种活性在很大程度上是由于gli 1，其表达是完全依赖于Hh信号在小鼠，但不是在斑马鱼。这些结果揭示了一个保守的要求纤毛在转导的活性的上游调节Hh信号，但不同的表型效应，由于差异调节和不同的作用，转录介质。
Cilia have been implicated in Hedgehog (Hh) and Wnt signaling in mouse but not in Drosophila. To determine whether the role of cilia is conserved in zebrafish, we generated maternal-zygotic (MZ) oval (ovl; ift88) mutants that lack all cilia. MZovl mutants display normal canonical and non-canonical Wnt signaling but show defects in Hh signaling. As in mouse, zebrafish cilia are required to mediate the activities of Hh, Ptc, Smo and PKA. However, in contrast to mouse Ift88 mutants, which show a dramatic reduction in Hh signaling, zebrafish MZovl mutants display dampened, but expanded, Hh pathway activity. This activity is largely due to gli1, the expression of which is fully dependent on Hh signaling in mouse but not in zebrafish. These results reveal a conserved requirement for cilia in transducing the activity of upstream regulators of Hh signaling but distinct phenotypic effects due to differential regulation and differing roles of transcriptional mediators.