The small GTPase RhoV is an essential regulator of neural crest induction in Xenopus

The small GTPase RhoV is an essential regulator of neural crest induction in Xenopus
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DOI:
10.1016/j.ydbio.2007.07.031
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发表时间:
2007-10-01
影响因子:
2.7
通讯作者:
Faure, Sandrine
Faure, Sandrine
中科院分区:
生物学3区
文献类型:
--
作者:
Guemar, Linda;Barbara, Pascal de Santa;Faure, Sandrine

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在脊椎动物中,GTPases的Rho家族由20个成员组成,它们调节各种细胞功能,包括肌动蛋白细胞骨架动力学、细胞粘附和运动、细胞生长和存活、基因转录和膜运输。为了全面了解Rho在生理上皮-间质转化中的作用,我们进行了基于原位杂交的筛选,以鉴定非洲爪蟾神经嵴细胞中表达的Rho成员,我们之前报道了RhoB在迁移阶段的表达。在本研究中,我们发现RhoV是一种早期表达的神经嵴标记物,并提供证据表明其活性对神经嵴细胞诱导至关重要。RhoV mRNA是母性表达的,并在原肠胚形成后不久在神经嵴形成区积累。通过注射反义morpholino,我们发现在神经发育阶段,RhoV缺失会损害神经嵴标记物Sox9、Slug或Twist的表达,但对蜗牛诱导没有影响。在尾芽期,RhoV基因敲低导致颅神经嵴衍生结构的显著丧失。所有这些缺陷都是由异位野生型RhoV修复的,其自身的过表达扩大了神经嵴的范围。我们的发现揭示了一个前所未有的Rho功能在控制神经嵴细胞规范的途径。(C) 2007爱思唯尔公司版权所有。
In vertebrates, the Rho family of GTPases is made of 20 members which regulate a variety of cellular functions, including actin cytoskeleton dynamics, cell adhesion and motility, cell growth and survival, gene transcription and membrane trafficking. To get a comprehensive view of Rho implication in physiological epithelial-mesenchymal transition, we carried out an in situ hybridization-based screen to identify Rho members expressed in Xenopus neural crest cells, in which we previously reported RhoB expression at the migrating stage. In the present study, we identify RhoV as an early expressed neural crest marker and provide evidence that its activity is essential for neural crest cell induction. RhoV mRNA is maternally expressed and accumulates shortly after gastrulation in the neural crest forming region. Using antisense morpholino injection, we show that at neurula stages, RhoV depletion impairs expression of the neural crest markers Sox9, Slug or Twist but has no effect on Snail induction. At the tailbud stage, RhoV knockdown causes a dramatic loss of cranial neural crest derived structures. All these defects are rescued by ectopic wildtype RhoV, whose overexpression on its own expands the neural crest territory. Our findings disclose an unprecedented Rho function in pathways that control neural crest cells specification. (C) 2007 Elsevier Inc. All rights reserved.