Frizzled7 mediates canonical Wnt signaling in neural crest induction
Frizzled7 mediates canonical Wnt signaling in neural crest induction
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DOI：
10.1016/j.ydbio.2006.06.037
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发表时间：
2006-10-01
影响因子：
2.7
通讯作者：
Wheeler, Grant N.
中科院分区：
文献类型：
--
作者：
Abu-Elmagd, Muhammad;Garcia-Morales, Carla;Wheeler, Grant N.
神经嵴是一个多能细胞群，从神经管的背侧边缘迁移到胚胎的各个部分，在那里它分化成各种不同的细胞类型。神经嵴的初始诱导由BMP、Wnt、FGF、视黄酸和Notch/Delta信号传导的组合介导。神经嵴诱导的双信号模型表明，BMP信号诱导能力成为神经嵴。第二个信号涉及Wnt通过经典途径起作用，并导致神经嵴标记物如蛞蝓的表达。来自神经板、非神经外胚层和近轴中胚层的Wnt信号都被认为在神经嵴诱导中起作用。我们展示了爪蟾是卷曲的？（Xfz 7）在包括早期神经嵴祖细胞的背外胚层中表达，并且是Wnt诱导信号的关键介质。我们证明，XFZ 7的表达诱导响应BMP拮抗剂，头蛋白，XFZ 7可以诱导神经嵴特异性基因在头蛋白处理的外胚层外植体（动物帽）。Xfz 7的吗啉代介导的或显性负抑制抑制在动物帽测定中和在整个胚胎中抑制Wnt诱导的Xslug表达，导致神经嵴衍生的色素细胞的损失。全长Xfz 7挽救了吗啉代诱导的表型，活化的β-连环蛋白也是如此，这表明Xfz 7通过经典途径进行信号传导。因此，我们表明，XFZ 7是由BMP拮抗作用调节，并需要在发育中的脊椎动物胚胎的神经嵴诱导Wnt。(c)2006年爱思唯尔公司All rights reserved.
The neural crest is a multipotent cell population that migrates from the dorsal edge of the neural tube to various parts of the embryo where it differentiates into a remarkable variety of different cell types. Initial induction of neural crest is mediated by a combination of BMP, Wnt, FGF, Retinoic acid and Notch/Delta signaling. The two-signal model for neural crest induction suggests that BMP signaling induces the competence to become neural crest. The second signal involves Wnt acting through the canonical pathway and leads to expression of neural crest markers such as slug. Wnt signals from the neural plate, non-neural ectoderm and paraxial mesoderm have all been suggested to play a role in neural crest induction. We show that Xenopus frizzled? (Xfz7) is expressed in the dorsal ectoderm including early neural crest progenitors and is a key mediator of the Wnt inductive signal. We demonstrate that Xfz7 expression is induced in response to a BMP antagonist, noggin, and that Xfz7 can induce neural crest specific genes in noggin-treated ectodermal explants (animal caps). Morpholino-mediated or dominant negative inhibition of Xfz7 inhibits Wnt induced Xslug expression in the animal cap assay and in the whole embryo leading to a loss of neural crest derived pigment cells. Full-length Xfz7 rescues the morpholino-induced phenotype, as does activated (beta-catenin, suggesting that Xfz7 is signaling through the canonical pathway. We therefore demonstrate that Xfz7 is regulated by BMP antagonism and is required for neural crest induction by Wnt in the developing vertebrate embryo. (c) 2006 Elsevier Inc. All rights reserved.