RNA helicase Mov10 is essential for gastrulation and central nervous system development.

RNA helicase Mov10 is essential for gastrulation and central nervous system development.
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DOI:
10.1002/dvdy.24615
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发表时间:
2018-04
期刊:
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子:
--
通讯作者:
Ceman S
Ceman S
中科院分区:
其他
文献类型:
--
作者:
Skariah G;Perry KJ;Drnevich J;Henry JJ;Ceman S

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Mov 10是一种RNA解旋酶,调节Argonaute 2进入mRNA中的microRNA识别元件。我们研究了Mov 10在非洲爪蟾发育中的作用,并显示Mov 10在原肠胚形成和中枢神经系统发育中的关键作用。使用翻译阻断吗啡来敲除非洲爪蟾胚胎中的母体Mov 10会导致原肠胚形成以及脊索和近轴中胚层发育缺陷,并且无法形成神经元。Mov 10敲除胚胎的RNA测序显示,与第10.5阶段的对照相比,许多mRNA显著上调(包括与细胞骨架、粘附和细胞外基质相关的mRNA,这些mRNA参与了这些形态发生过程)。此外,miR-427靶mRNA,细胞周期蛋白A1的降解在Mov 10敲低中延迟。这些缺陷表明,Mov 10在miRNA介导的调节母体到合子转变中的作用可能导致多效性效应,从而导致原肠胚形成缺陷。此外,合子Mov 10的敲除表明,它是非洲爪蟾正常头部,眼睛和大脑发育所必需的,与最近在小鼠中的研究一致。Mov 10对原肠胚形成和正常CNS发育至关重要。
Mov10 is an RNA helicase that modulates access of Argonaute 2 to microRNA recognition elements in mRNAs. We examined the role of Mov10 in Xenopus laevis development and show a critical role for Mov10 in gastrulation and in the development of the central nervous system. Knockdown of maternal Mov10 in Xenopus embryos using a translation blocking morpholino led to defects in gastrulation and the development of notochord and paraxial mesoderm, and a failure to neurulate. RNA sequencing of the Mov10 knockdown embryos showed significant upregulation of many mRNAs when compared to controls at stage 10.5 (including those related to the cytoskeleton, adhesion, and extracellular matrix, which are involved in those morphogenetic processes). Additionally, the degradation of the miR-427 target mRNA, cyclin A1, was delayed in the Mov10 knockdowns. These defects suggest that Mov10’s role in miRNA-mediated regulation of the maternal to zygotic transition could lead to pleiotropic effects that cause the gastrulation defects. Additionally, the knockdown of zygotic Mov10 showed that it was necessary for normal head, eye and brain development in Xenopus consistent with a recent study in the mouse. Mov10 is essential for gastrulation and normal CNS development.
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