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RNA解旋酶Mov10对原肠胚形成和中枢神经系统发育至关重要。

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

作者信息

Skariah Geena, Perry Kimberly J, Drnevich Jenny, Henry Jonathan J, Ceman Stephanie

机构信息

Neuroscience Program, University of Illinois-Urbana Champaign, Urbana, Illinois.

Cell and Developmental Biology, University of Illinois-Urbana Champaign, Urbana, Illinois.

出版信息

Dev Dyn. 2018 Apr;247(4):660-671. doi: 10.1002/dvdy.24615. Epub 2018 Jan 18.

Abstract

BACKGROUND

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 (CNS).

RESULTS

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 with 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.

CONCLUSIONS

Mov10 is essential for gastrulation and normal CNS development. Developmental Dynamics 247:660-671, 2018. © 2017 Wiley Periodicals, Inc.

摘要

背景

Mov10是一种RNA解旋酶,可调节AGO2对mRNA中微小RNA识别元件的识别。我们研究了Mov10在非洲爪蟾发育中的作用,并发现Mov10在原肠胚形成和中枢神经系统(CNS)发育中起关键作用。

结果

使用翻译阻断吗啉代寡核苷酸敲低非洲爪蟾胚胎中的母体Mov10,导致原肠胚形成以及脊索和近轴中胚层发育出现缺陷,并且无法形成神经胚。与10.5期的对照相比,Mov10敲低胚胎的RNA测序显示许多mRNA显著上调(包括那些与细胞骨架、黏附及细胞外基质相关的mRNA,它们参与了这些形态发生过程)。此外,在Mov10敲低的胚胎中,miR - 427靶mRNA细胞周期蛋白A1的降解延迟。这些缺陷表明,Mov10在微小RNA介导的母型向合子型转变调控中的作用可能导致多效性效应,从而引起原肠胚形成缺陷。此外,敲低合子型Mov10表明,它对于非洲爪蟾正常的头部、眼睛和大脑发育是必需的,这与最近在小鼠中的一项研究结果一致。

结论

Mov10对原肠胚形成和正常的中枢神经系统发育至关重要。《发育动力学》247:660 - 671,2018年。©2017威利期刊公司。

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