Cilia-driven asymmetric Hedgehog signalling determines the amphioxus left-right axis by controlling Dand5 expression
Cilia-driven asymmetric Hedgehog signalling determines the amphioxus left-right axis by controlling Dand5 expression
复制标题
纤毛驱动的不对称 Hedgehog 信号通过控制 Dand5 表达来决定文昌鱼左右轴
DOI：
10.1242/dev.182469
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发表时间：
2020-01-01
期刊：
影响因子：
4.6
通讯作者：
Li, Guang
中科院分区：
文献类型：
--
作者：
Zhu, Xin;Shi, Chenggang;Li, Guang
纤毛旋转驱动的节流是脊椎动物左右对称性破坏的关键。然而，流动信号被翻译成不对称基因表达的机制尚未得到充分解决。在这里，我们表明，刺猬（Hh）信号是不对称激活（L<R）的区域中，初始不对称Dand 5的表达被检测到。野生型胚胎左侧Hh信号的上调诱导左侧异位Dand 5表达，Hh纯合突变体中Hh信号的单侧恢复诱导Hh信号恢复侧的Dand 5表达。免疫荧光分析结果显示，Hh融合蛋白在神经胚早期不对称地富集于右前近轴中胚层。使用甲基纤维素（MC）抑制胚胎纤毛运动阻断右侧的Hh蛋白富集，并使Dand 5表达和器官定位沿L-R轴沿着随机化。这些研究结果提出了一个模型，表明纤毛运动是至关重要的对称性破坏文昌鱼通过不对称的Hh蛋白运输。所得的不对称Hh信号传导提供了诱导不对称Dand 5表达的线索。这篇文章有一个相关的“报纸背后的人”采访。突出显示的文章：纤毛运动及其诱导的不对称Hh信号是文昌鱼左右不对称性建立的两个关键调节因子，可能代表了后口动物进化上保守的机制。
ABSTRACT Cilia rotation-driven nodal flow is crucial for the left-right (L-R) break in symmetry in most vertebrates. However, the mechanism by which the flow signal is translated to asymmetric gene expression has been insufficiently addressed. Here, we show that Hedgehog (Hh) signalling is asymmetrically activated (L<R) in the region in which initial asymmetric Dand5 expression is detected. Upregulation of Hh signalling on the left side of wild-type embryos induces ectopic Dand5 expression on the left side, and the unilateral recovery of Hh signalling in Hh homozygous mutants induces Dand5 expression in the Hh signal recovery side. Immunofluorescence analysis results revealed that Hh fusion protein is asymmetrically enriched in the anterior-right paraxial mesoderm at the early neurula stage. Inhibiting embryonic cilia motility using methylcellulose (MC) blocks Hh protein enrichment on the right hand side and randomizes Dand5 expression and organ positioning along the L-R axis. These findings present a model showing that cilia movement is crucial for the symmetry breaks in amphioxus through asymmetric Hh protein transport. The resultant asymmetric Hh signalling provides a clue into the induction of asymmetric Dand5 expression. This article has an associated ‘The people behind the papers’ interview. Highlighted Article: Cilia movement and its induced asymmetric Hh signalling are the two key regulators for the establishment of amphioxus left-right asymmetry, likely representing an evolutionarily conserved mechanism in deuterostomes.