Hedgehog participates in the establishment of left-right asymmetry during amphioxus development by controlling Cerberus expression
Hedgehog participates in the establishment of left-right asymmetry during amphioxus development by controlling Cerberus expression
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Hedgehog通过控制Cerberus表达参与文昌鱼发育过程中左右不对称的建立
DOI：
10.1242/dev.157172
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发表时间：
2017-12-15
期刊：
影响因子：
4.6
通讯作者：
Wang, Yiquan
中科院分区：
文献类型：
--
作者：
Hu, Guangwei;Li, Guang;Wang, Yiquan
左右（LR）不对称的正确模式在双侧畸形的胚胎发育过程中是必不可少的。Hedgehog（Hh）信号通过调节Nodal表达在小鼠、鸡和海胆胚胎的LR不对称发育中发挥作用。在这项研究中，我们报告了一个新的调节机制Hh在LR不对称发育的文昌鱼胚胎。我们的研究结果表明，Hh −/−胚胎废除Cerberus（Cer）转录，双侧对称表达的Nodal，Lefty和Pitx。结果，Hh −/−突变体复制了左侧结构，失去了右侧特征，显示出异常的两侧对称的身体平面。这些LR的形态和基因表达的缺陷可以通过注射Hh mRNA来挽救。我们的研究结果表明，Hh参与文昌鱼LR图案通过控制Cer基因的表达。然而，奇怪的是，Hh信号的上调未能改变Cer表达模式或LR形态在文昌鱼胚胎，表明Hh可能不提供Cer表达的不对称线索。此外，Hh是文昌鱼开口所必需的，暗示了文昌鱼与脊椎动物口腔发育之间的同源关系。总结：在文昌鱼的Hh信号中断导致Cer表达和Nodal，Pitx和Lefty的双边表达的损失，揭示了在这个古老的脊索动物LR模式的新作用。
Correct patterning of left-right (LR) asymmetry is essential during the embryonic development of bilaterians. Hedgehog (Hh) signaling is known to play a role in LR asymmetry development of mouse, chicken and sea urchin embryos by regulating Nodal expression. In this study, we report a novel regulatory mechanism for Hh in LR asymmetry development of amphioxus embryos. Our results revealed that Hh−/− embryos abolish Cerberus (Cer) transcription, with bilaterally symmetric expression of Nodal, Lefty and Pitx. In consequence, Hh−/− mutants duplicated left-side structures and lost right-side characters, displaying an abnormal bilaterally symmetric body plan. These LR defects in morphology and gene expression could be rescued by Hh mRNA injection. Our results indicate that Hh participates in amphioxus LR patterning by controlling Cer gene expression. Curiously, however, upregulation of Hh signaling failed to alter the Cer expression pattern or LR morphology in amphioxus embryos, indicating that Hh might not provide an asymmetric cue for Cer expression. In addition, Hh is required for mouth opening in amphioxus, hinting at a homologous relationship between amphioxus and vertebrate mouth development. Summary: Disruption of Hh signaling in amphioxus causes loss of Cer expression and bilateral expression of Nodal, Pitx and Lefty, revealing a novel role in LR patterning in this ancient chordate.