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Rab23 regulates Nodal signaling in vertebrate left-right patterning independently of the Hedgehog pathway

机译:Rab23独立于刺猬通路调节脊椎动物左右模式中的节点信号。

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摘要

Asymmetric fluid flow in the node and Nodal signaling in the left lateral plate mesoderm (LPM) drive left-right patterning of the mammalian body plan. However, the mechanisms linking fluid flow to asymmetric gene expression in the LPM remain unclear. Here we show that the small GTPase Rab23, known for its role in Hedgehog signaling, plays a separate role in Nodal signaling and left-right patterning in the mouse embryo. Rab23 is not required for initial symmetry breaking in the node, but it is required for expression of Nodal and Nodal target genes in the LPM. Microinjection of Nodal protein and transfection of Nodal cDNA in the embryo indicate that Rab23 is required for the production of functional Nodal signals, rather than the response to them. Using gain- and loss-of function approaches, we show that Rab23 plays a similar role in zebrafish, where it is required in the teleost equivalent of the mouse node, Kupffer's vesicle. Collectively, these data suggest that Rab23 is an essential component of the mechanism that transmits asymmetric patterning information from the node to the LPM.
机译:淋巴结中的不对称流体流动和左侧中板中胚层(LPM)中的Nodal信号驱动哺乳动物身体计划的左右模式。但是,将流体流动与LPM中不对称基因表达联系起来的机制仍不清楚。在这里,我们显示了小GTPase Rab23(以其在刺猬信号中的作用而闻名)在小鼠胚胎的Nodal信号和左右模式中起着单独的作用。 Rab23对于在节点中初始对称性破坏不是必需的,但对于在LPM中表达Nodal和Nodal目标基因则是必需的。在胚胎中显微注射Nodal蛋白和Nodal cDNA转染表明Rab23是产生功能性Nodal信号所必需的,而不是对它们的响应。使用增益和损失函数方法,我们证明Rab23在斑马鱼中起着相似的作用,而斑马鱼的硬骨等效物是小鼠结节Kupffer的囊泡。总的来说,这些数据表明Rab23是从节点向LPM传输非对称模式信息的机制的重要组成部分。

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